ALBERT

Description: Transmetallation example in reaction of tetrahydothiopyran-4-one lithium enolate with methyl bromoacetate Content Type Journal Article Category Short Communications Pages 304-305 DOI 10.1134/S107042801202025X Authors R. F. Valeev, Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia R. F. Bikzhanov, Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia M. S. Miftakhov, Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    The reaction of ( Z )-2-amino-1,4-diarylbut-2-en-1,4-diones with oxalyl chloride led to the formation of 1-aryl-4,5-diaroyl-1 H -pyrrole-2,3-diones that at the thermal decarbonylation gave aroyl( N -arylimidoyl)ketenes which underwent stabilization by molecular cyclization into 2,3-diaroylquinolin-4(1 H )-ones. Content Type Journal Article Pages 249-252 DOI 10.1134/S1070428012020145 Authors P. S. Silaichev, Institute of Natural Sciences at Perm State University, Perm, 614990 Russia N. V. Kudrevatykh, Perm State University, Perm, Russia A. N. Maslivets, Institute of Natural Sciences at Perm State University, Perm, 614990 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    The oxidation with SeO 2 of a methyl group linked to an sp 2 -hybridized carbon in the product of the intramolecular iodoetherification of cis -carveol afforded (1 R ,5 R ,7 S )-7-iodomethyl-7-methyl-6-oxabicyclo[3.2.1]-oct-3-en-4-carbaldehyde and [(1 R ,5 R ,7 S )-7-iodomethyl-7-methyl-6-oxabicyclo[3.2.1]oct-3-en-4-yl]methanol that were oxidized to methyl (1 R ,5 R ,7 S )-7-iodomethyl-7-methyl-6-oxabicyclo[3.2.1]oct-3-en-4-carboxylate. The latter by the Zn-promoted opening of the γ-oxide ring was converted into the target chiral block, methyl (4 R ,6 R )-6-hydroxy-4-(prop-1-en-2-yl)cyclohex-1-encarboxylate. Content Type Journal Article Pages 180-183 DOI 10.1134/S1070428012020054 Authors F. A. Gimalova, Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia G. M. Khalikova, Bashkir State University, Ufa, Russia S. A. Torosyan, Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia D. Z. Akhmetshina, Bashkir State University, Ufa, Russia M. S. Miftakhov, Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences, Ufa, 450054 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description: Formation of N,N ′-Di(5-alkoxycarbonyl-5-methyl-2-oxo-1-phenyl-2,5-dihydro-1 H -pyrrol-3-yl)- N,N ′-diphenyloxalylamides in the synthesis of alkyl 4-methyl-2,3,6-trioxo-1,5-diphenyl-1,2,3,4,5,6-hexahydropyrrolo[3,4- b ]pyrrole-4-carboxylates Content Type Journal Article Category Short Communications Pages 296-298 DOI 10.1134/S1070428012020224 Authors V. L. Gein, Perm State Pharmaceutical Academy of the Federal Agency of Health Protection and Social Development, Perm, 614000 Russia R. O. Dyrenkov, Perm State Pharmaceutical Academy of the Federal Agency of Health Protection and Social Development, Perm, 614000 Russia N. A. Kornienko, Perm State Pharmaceutical Academy of the Federal Agency of Health Protection and Social Development, Perm, 614000 Russia M. I. Vakhrin, Perm State Pharmaceutical Academy of the Federal Agency of Health Protection and Social Development, Perm, 614000 Russia P. A. Slepukhin, Postovsky Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, Yekaterinburg, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    By the XRD analysis the structure was established of 1-(7,8-dimethyl-4-chloroquinolin-2-yl)-2-[3,5-di( tert -butyl)-6-oxo-6 H -pyran-2-yl]ethane-1,2-dione formed as a result of the oxidation of 3,5-di( tert -butyl)-6-[( Z )-2-(quinolin-2-yl)-1-hydroxyethen-1-yl]pyran-2-ones. By the cyclic voltammetry the oxidation of 1-(quinolin-2-yl)-2-(pyran-2-yl)ethane-1,2-dione derivatives was shown to proceed in two stages. Content Type Journal Article Pages 151-157 DOI 10.1134/S1070428012020017 Authors V. V. Tkachev, Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow oblast, 142432 Russia G. V. Shilov, Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow oblast, 142432 Russia S. M. Aldoshin, Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow oblast, 142432 Russia E. A. Gusakov, Institute of Physical and Organic Chemistry at the Southern Federal University, Rostov-on-Don, Russia Yu. A. Sayapin, Southern Scientific Center, Russian Academy of Sciences, Rostov-on-Don, 344006 Russia A. A. Bumber, Southern Scientific Center, Russian Academy of Sciences, Rostov-on-Don, 344006 Russia V. N. Komissarov, Institute of Physical and Organic Chemistry at the Southern Federal University, Rostov-on-Don, Russia V. I. Minkin, Institute of Physical and Organic Chemistry at the Southern Federal University, Rostov-on-Don, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description: Dehydrohalogenation of haloalkylarenes in the synthesis of alkenylaromatic hydrocarbons Content Type Journal Article Category Short Communications Pages 293-295 DOI 10.1134/S1070428012020212 Authors A. M. Magerramov, Baku State University, Baku, 5004 Azerbaijan M. N. Magerramov, Baku State University, Baku, 5004 Azerbaijan I. A. Aliev, Baku State University, Baku, 5004 Azerbaijan A. M. Mustafaev, Institute of Polymer Materials, National Academy of Sciences of Azerbaijan, Sumgaiyt, Az-5004 Azerbaijan U. F. Askerova, Baku State University, Baku, 5004 Azerbaijan Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    Proceeding from 2-aminoquinoxaline-3-carbonitrile 1,4-dioxides new derivatives of quinoxaline and quinoxaline 1,4-dioxide were synthesized containing in the position 3 of the quinoxaline fragment 1,2,4-oxadiazole and tetrazole rings. The acylation of 2-amino- N ′-hydroxyquinoxaline-3-carbox imidoamide 1,4-dioxide was investigated. Content Type Journal Article Pages 278-283 DOI 10.1134/S1070428012020194 Authors O. B. Laskina, St. Petersburg State Technological Institute (Technical University), St. Petersburg, 190013 Russia S. F. Mel’nikova, St. Petersburg State Technological Institute (Technical University), St. Petersburg, 190013 Russia I. V. Tselinskii, St. Petersburg State Technological Institute (Technical University), St. Petersburg, 190013 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    Cyclothiomethylation was performed of heterochain (O, S-S, NH) α,ω-diamines with formaldehyde and H 2 S in aqueous medium at 20–60°C to obtain new α,ω-bis(1,3,5-dithiazinanes). The cyclocondensation of N-(3-aminopropyl)butane-1,4-diamine (spermidine), formaldehyde, and H 2 S proceeds efficiently in the medium of BuOH-H 2 O at 0°C and leads to the formation of previously unknown O,S-containing macroheterocycle, 1,7-dioxa-3,5,9,11-tetrathiacyclododecane. A fungicidal activity was found in 5,5′-(3,6-dioxaoctane-1,8-diyl)bis-1,3,5-dithiazinane with respect to microscopic fungi affecting agriculture. Content Type Journal Article Pages 202-208 DOI 10.1134/S107042801202008X Authors V. R. Akhmetova, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia E. B. Rakhimova, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia A. B. Minnebaev, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia R. V. Kunakova, Ufa State Academy of Economics and Service, Ufa, Russia N. F. Galimzyanova, Institute of Biology, Ufa Scientific Center, Russian Academy of Sciences, Ufa, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    Spectral and quantum-chemical investigation of ortho - and peri -hydroxy-substituted aldehydes, 1,5-naphthalenediol derivatives, was carried out. An unusual spin-spin coupling through an intramolecular hydrogen bond was discovered in the molecule of 1,5-dihydroxynaphthalene-4,8-dicarbaldehyde. It was shown that this dialdehyde is involved into the ring-chain tautomerism. The position of this equilibrium was examined depending on the temperature and the solvent polarity. The effect of the solvent polarity on the benzoid-quinoid tautomerism in the dihydroxynaphthalene-2,6-dicarbaldehyde was established. By the method of quantum-chemical calculations the relative energy stability and conformational structure of dialdehydes were revealed. Content Type Journal Article Pages 241-248 DOI 10.1134/S1070428012020233 Authors V. V. Mezheritskii, Institute of Physical and Organic Chemistry at the Southern Federal University, Rostov-on-Don, 344090 Russia M. S. Korobov, Institute of Physical and Organic Chemistry at the Southern Federal University, Rostov-on-Don, 344090 Russia O. M. Golyanskaya, Institute of Physical and Organic Chemistry at the Southern Federal University, Rostov-on-Don, 344090 Russia N. I. Omelichkin, Institute of Physical and Organic Chemistry at the Southern Federal University, Rostov-on-Don, 344090 Russia L. G. Minyaeva, Institute of Physical and Organic Chemistry at the Southern Federal University, Rostov-on-Don, 344090 Russia G. S. Borodkin, Institute of Physical and Organic Chemistry at the Southern Federal University, Rostov-on-Don, 344090 Russia A. A. Milov, Southern Scientific Center, Russian Academy of Sciences, Rostov-on-Don, Russia A. V. Tsukanov, Southern Scientific Center, Russian Academy of Sciences, Rostov-on-Don, Russia A. D. Dubonosov, Southern Scientific Center, Russian Academy of Sciences, Rostov-on-Don, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    The absolute configuration of α-hydroxyaldehyde obtained from verbenol epoxide in the presence of clay was determined. Two new Schiff bases were synthesized from the aldehyde obtained. The compounds can be used as ligands in the asymmetric vanadium-catalyzed oxidation of sulfides to sulfoxides. The structure of initial sulfides significantly affects the value of the enantiomeric excess in the obtained sulfoxides: the highest enantiomeric excess is observed in the oxidation of thioanisole. Content Type Journal Article Pages 214-220 DOI 10.1134/S1070428012020108 Authors I. V. Il’ina, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia E. A. Koneva, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia D. V. Korchagina, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia G. E. Sal’nikov, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia A. M. Genaev, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia K. P. Volcho, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia N. F. Salakhutdinov, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    Asymmetric syntheses were performed of neomenthanesulfinamide in the yield of 60% and de 74%, of neomenthanesulfinaldimines and N-substituted neomenthanesulfinamides in 22–80 and 40–90% yields respectively. Content Type Journal Article Pages 184-192 DOI 10.1134/S1070428012020066 Authors E. S. Izmest’ev, Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, 167982 Russia D. V. Sudarikov, Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, 167982 Russia S. A. Rubtsova, Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, 167982 Russia P. A. Slepukhin, Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences, Yekaterinburg, Russia A. V. Kuchin, Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences, Syktyvkar, 167982 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    Efficient method was developed for thiols aminomethylation using N,N,N ′, N ′-tetra-methylmethanediamine in the presence of Sm and Fe salts. Aminosulfides were obtained in high yields and selectivity. Content Type Journal Article Pages 175-179 DOI 10.1134/S1070428012020042 Authors R. R. Khairullina, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia B. F. Akmanov, Ufa State Academy of Economics and Service, Ufa, Russia T. V. Tyumkina, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia R. V. Kunakova, Ufa State Academy of Economics and Service, Ufa, Russia A. G. Ibragimov, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Ufa, 450075 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    Reactions of 2-(4-hydroxyarylamino)-1,4-naphthoquinones with cerium ammonium nitrate or pyridinium chlorochromate depending on the structure of initial substrate and the type of reagent led to the formation of 2-chloro-3-(4-cyclohexa-2,5-dienylideneamino)-1,4-dihydronaphthalene-1,4-diones, 2-(4-hydroxy-3-nitrophenylamino)-1,4-naphthaquinones, and also to simultaneous oxidation and chlorination. Content Type Journal Article Pages 234-240 DOI 10.1134/S1070428012020121 Authors A. E. Devyashina, Astaf’ev Krasnoyarsk State Pedagogical University, Krasnoyarsk, 660049 Russia L. M. Gornostaev, Astaf’ev Krasnoyarsk State Pedagogical University, Krasnoyarsk, 660049 Russia Yu. V. Gatilov, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, Novosibirsk, 630090 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    By the reaction of acetylacetone and arylazoacetylacetones with 4-iminothiazolidin-2-one thiazolo[4,5- b ]pyridines were obtained in good yields. Optimum reaction conditions were chosen and some properties of compounds obtained were studied. Content Type Journal Article Pages 268-272 DOI 10.1134/S1070428012020170 Authors T. I. Chaban, Danylo Halytsky Lviv National Medical University, L’vov, 79010 Ukraine B. S. Zimenkovskii, Danylo Halytsky Lviv National Medical University, L’vov, 79010 Ukraine I. D. Komaritsa, Danylo Halytsky Lviv National Medical University, L’vov, 79010 Ukraine I. G. Chaban, Danylo Halytsky Lviv National Medical University, L’vov, 79010 Ukraine Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    It was shown by quantum-chemical method B3LYP/6-311++G(df,p) that in the autocatalytic reaction the molecules of methyl carbamate formed prereaction complexes with the monomer and dimer of methanol. The complexes possess higher electron-donor properties than free alcohol molecules thus increasing the activity of complexes in the reaction with isocyanates. The products of the autocatalytic reaction are new molecules of carbamate and azomethinenol. The conversions occur through concerted asymmetric late transition states. The isomerization of azomethinenols into carbamates is catalyzed by molecules of alcohols and their associates. The autocatalytic reaction of isocyanates with alcohols becomes possible owing to the ability of alcohols to catalyze the mentioned isomerization. Content Type Journal Article Pages 158-163 DOI 10.1134/S1070428012020029 Authors A. Ya. Samuilov, Kazan State Technological University, Kazan, Russia T. A. Kamalov, Kazan State Technological University, Kazan, Russia F. B. Balabanova, Kazan State Technological University, Kazan, Russia Ya. D. Samuilov, Kazan State Technological University, Kazan, Russia A. I. Konovalov, Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences, Kazan, 420015 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description:    In reactions with sodium sulfinates of N-substituted 1,4-benzoquinone monoimines with the quinoid ring having free positions 2 and/or 6 the fraction of products of 1,4-addition of the sulfinate ion grows in the series ArSO 2 → MeSO 2 → CF 3 SO 2 . In the case of 2,6-dimethyl derivatives the 1,6-addition is preferable, and the amount of products of 6,1-addition decreases. Content Type Journal Article Pages 221-233 DOI 10.1134/S107042801202011X Authors A. P. Avdeenko, Donbass State Engineering Academy, Kramatorsk, 84313 Ukraine S. A. Konovalova, Donbass State Engineering Academy, Kramatorsk, 84313 Ukraine O. N. Mikhailichenko, Donbass State Engineering Academy, Kramatorsk, 84313 Ukraine S. V. Shelyazhenko, Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine V. V. Pirozhenko, Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine L. M. Yagupol’skii, Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 2

Description: New pathway of the reaction of hetareno[ a ]pyrrole-2,3-diones with NH nucleophiles Content Type Journal Article Category Short Communications Pages 145-146 DOI 10.1134/S1070428012010253 Authors L. V. Kuslina, Perm State University, ul. Bukireva 15, Perm, 614990 Russia I. V. Mashevskaya, Institute of Natural Sciences, Perm State University, ul. Genkelya 4, Perm, 614990 Russia P. A. Slepukhin, Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences, ul. S. Kovalevskoi 20, Yekaterinburg, 620219 Russia A. N. Maslivets, Perm State University, ul. Bukireva 15, Perm, 614990 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description: N -Methyl- N -(2-phenylethenyl)trifluoromethanesulfonamide Content Type Journal Article Category Short Communications Pages 141-142 DOI 10.1134/S107042801201023X Authors B. A. Shainyan, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia I. V. Ushakova, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description: Efficient regioselective synthesis of 3-substituted 6,7-dihydro-5 H -pyrrolo[1,2- c ][1,3]thiazol-4-ium bromides Content Type Journal Article Category Short Communications Pages 143-144 DOI 10.1134/S1070428012010241 Authors V. D. Dyachenko, Taras Shevchenko Lugansk National University, ul. Oboronnaya 2, Lugansk, 91011 Ukraine Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description:    Partial ozonolysis of ( S )-(−)-limonene in cyclohexane-methanol yields 1-methyl-4-(prop1-en-2-yl)-7,8,9-trioxabicyclo[4.2.1]nonane as a mixture of diastereoisomers at a ratio of 2: 3. Nitrogen-containing organic compounds (semicarbazide and hydroxylamine hydrochlorides) favor cyclization of intermediate ozonolysisreduction products, whereas the reduction with dimethyl sulfide, NaBH 4 , and NaBH(OAc) 3 follows conventional pattern. Content Type Journal Article Pages 18-24 DOI 10.1134/S1070428012010034 Authors G. Yu. Ishmuratov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Yu. V. Legostaeva, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia L. P. Botsman, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia G. V. Nasibullina, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia R. R. Muslukhov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia D. V. Kazakov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia G. A. Tolstikov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description:    Condensation of 1-phenylsulfanylpropan-2-one with 1,3,6,8-tetraazatricyclo[4.4.1.1 3,8 ]dodecane gave 1-phenylsulfanyl-3,6-diazahomoadamantan-9-one which was reduced to 1-phenylsulfanyl-3,6-diazahomoadamantane, and the latter was subjected to desulfurization over Raney nickel to obtain previously unknown 3,6-diazahomoadamantane. Heating of 9-phenyl-3,6-diazahomoadamantan-9-ols with Raney nickel resulted in reduction of the hydroxy group with formation of 9-phenyl-3,6-diazahomoadamantanes. Content Type Journal Article Pages 119-122 DOI 10.1134/S1070428012010198 Authors A. I. Kuznetsov, Lomonosov Academy of Fine Chemical Technology, pr. Vernadskogo 86, Moscow, 119571 Russia I. M. Senan, Lomonosov Academy of Fine Chemical Technology, pr. Vernadskogo 86, Moscow, 119571 Russia A. Kh. Shukkur, Lomonosov Academy of Fine Chemical Technology, pr. Vernadskogo 86, Moscow, 119571 Russia I. A. Azzheurova, Lomonosov Academy of Fine Chemical Technology, pr. Vernadskogo 86, Moscow, 119571 Russia T. M. Serova, Institute of Physiologically Active Substances, Russian Academy of Sciences, Chernogolovka, Moscow oblast, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description:    Sarkomycin A methyl esters and functionalized cyclopentane blocks for brefeldin A were synthesized starting from diastereoisomeric (1 R ,2 S )- and (1 S ,2 R )-2-hydroxymethyl- N -[(1 R )-1-phenylethyl]cyclopent-3-ene-1-carboxamides. Content Type Journal Article Pages 8-17 DOI 10.1134/S1070428012010022 Authors A. M. Gimazetdinov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia G. V. Ishmurzina, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia M. S. Miftakhov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description:    5-Phenyl( p -tolyl)isoxazole-3-carboxylic acids were synthesized starting from 3-hydroxyiminomethyl-5-phenyl( p -tolyl)isoxazoles, and their reactions with p -hydroxybenzaldehyde, vanillin, isovanillin, o -vanillin, and ethyl vanillin gave the corresponding esters. The latter were brought into condensation with aromatic amines to obtain Schiff bases which were reduced to amines. Content Type Journal Article Pages 127-136 DOI 10.1134/S1070428012010216 Authors V. I. Potkin, Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, ul. Surganova 13, Minsk, 220072 Belarus R. A. Gadzhily, Institute of Polymeric Materials, National Academy of Sciences of Azerbaijan, Sumgait, Azerbaijan E. A. Dikusar, Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, ul. Surganova 13, Minsk, 220072 Belarus S. K. Petkevich, Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, ul. Surganova 13, Minsk, 220072 Belarus N. A. Zhukovskaya, Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, ul. Surganova 13, Minsk, 220072 Belarus A. G. Aliev, Institute of Polymeric Materials, National Academy of Sciences of Azerbaijan, Sumgait, Azerbaijan Sh. F. Nagieva, Institute of Polymeric Materials, National Academy of Sciences of Azerbaijan, Sumgait, Azerbaijan Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description:    Reaction of 5-methyl-, 5-bromo-, and 5-iodoisatins with phosphoryl chloride gave the corresponding 2,8-disubstituted indolo[2,1- b ]quinazoline-6,12-diones in moderate yield. 5,7-Dichloroisatin failed to react with POCl 3 . Treatment of an equimolar mixture of isatin and 5-bromoisatin with POCl 3 afforded indolo[2,1- b ]-quinazoline-6,12-dione (tryptanthrin), 2,8-dibromoindolo[2,1- b ]quinazoline-6,12-dione, and two isomeric monobromo-substituted tryptanthrin derivatives, the 2-bromo isomer prevailing. Content Type Journal Article Pages 123-126 DOI 10.1134/S1070428012010204 Authors T. V. Moskovkina, Far East Federal University, ul. Oktyabr’skaya 27, Vladivostok, 690600 Russia A. I. Kalinovskii, Pacific Institute of Bioorganic Chemistry, Far East Division, Russian Academy of Sciences, Vladivostok, Russia V. V. Makhan’kov, Pacific Institute of Bioorganic Chemistry, Far East Division, Russian Academy of Sciences, Vladivostok, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description: New synthesis of 2-aminobenzo[ b ]selenophenes from 4-(2-chloroaryl)-1,2,3-selenadiazoles Content Type Journal Article Category Short Communications Pages 147-149 DOI 10.1134/S1070428012010265 Authors M. L. Petrov, St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia A. G. Lyapunova, St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia D. A. Androsov, St. Petersburg State Institute of Technology, Moskovskii pr. 26, St. Petersburg, 190013 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description:    Cycloalumination of cycloalkynes with triethylaluminum in the presence of zirconium complexes was performed for the first time, and new bicyclic aluminacyclopentenes were obtained in 74–94% yield. Content Type Journal Article Pages 1-7 DOI 10.1134/S1070428012010010 Authors V. A. D’yakonov, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia L. F. Galimova, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia T. V. Tyumkina, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia U. M. Dzhemilev, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description:    Previously unknown diastereoisomeric sulfoxides were synthesized by asymmetric oxidation of 2-neomenthylsulfanyl-substituted 1 H -imidazole, 1-methyl-1 H -imidazole, and 1 H -benzimidazole. Content Type Journal Article Pages 113-118 DOI 10.1134/S1070428012010186 Authors M. Ya. Demakova, Institute of Chemistry, Komi Research Center, Ural Division, Russian Academy of Sciences, Pervomaiskaya 48, Syktyvkar, 167982 Russia D. V. Sudarikov, Institute of Chemistry, Komi Research Center, Ural Division, Russian Academy of Sciences, Pervomaiskaya 48, Syktyvkar, 167982 Russia S. A. Rubtsova, Institute of Chemistry, Komi Research Center, Ural Division, Russian Academy of Sciences, Pervomaiskaya 48, Syktyvkar, 167982 Russia P. A. Slepukhin, Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences, ul. S. Kovalevskoi 20, Yekaterinburg, 620219 Russia A. V. Kutchin, Institute of Chemistry, Komi Research Center, Ural Division, Russian Academy of Sciences, Pervomaiskaya 48, Syktyvkar, 167982 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description:    Oxidation of 1,1′-[3-(methylsulfanylmethyl)tetrahydro-2 H -thiopyran-3,5-diyl]diethanone with equivalent amounts of potassium iodate in glacial acetic acid and hydrogen peroxide in tetrahydrofuran and chloroform gave the corresponding mono- and disulfoxides and disulfone, respectively. Reactions of the title compound with sodium tetrahydridoborate and hydroxylamine hydrochloride afforded mono- and dihydroxy derivatives and monooxime, respectively. Content Type Journal Article Pages 94-98 DOI 10.1134/S1070428012010149 Authors L. A. Baeva, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia T. S. Nikitina, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia A. A. Fatykhov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia E. G. Galkin, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia N. K. Lyapina, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 1

Description: Frontonasal dysplasia (FND) refers to a class of midline facial malformations caused by abnormal development of the facial primordia. The term encompasses a spectrum of severities but characteristic features include combinations of ocular hypertelorism, malformations of the nose and forehead and clefting of the facial midline. Several recent studies have drawn attention to the importance of Alx homeobox transcription factors during craniofacial development. Most notably, loss of Alx1 has devastating consequences resulting in severe orofacial clefting and extreme microphthalmia. In contrast, mutations of Alx3 or Alx4 cause milder forms of FND. Whilst Alx1 , Alx3 and Alx4 are all known to be expressed in the facial mesenchyme of vertebrate embryos, little is known about the function of these proteins during development. Here, we report the establishment of a zebrafish model of Alx -related FND. Morpholino knock-down of zebrafish alx1 expression causes a profound craniofacial phenotype including loss of the facial cartilages and defective ocular development. We demonstrate for the first time that Alx1 plays a crucial role in regulating the migration of cranial neural crest (CNC) cells into the frontonasal primordia. Abnormal neural crest migration is coincident with aberrant expression of foxd3 and sox10 , two genes previously suggested to play key roles during neural crest development, including migration, differentiation and the maintenance of progenitor cells. This novel function is specific to Alx1, and likely explains the marked clinical severity of Alx1 mutation within the spectrum of Alx -related FND.

Description: Activating somatic and germline mutations of closely related RAS genes (H, K, N) have been found in various types of cancer and in patients with developmental disorders, respectively. The involvement of the RAS signalling pathways in developmental disorders has recently emerged as one of the most important drivers in RAS research. In the present study, we investigated the biochemical and cell biological properties of two novel missense KRAS mutations (Y71H and K147E). Both mutations affect residues that are highly conserved within the RAS family. KRAS Y71H showed no clear differences to KRAS wt , except for an increased binding affinity for its major effector, the RAF1 kinase. Consistent with this finding, even though we detected similar levels of active KRAS Y71H when compared with wild-type protein, we observed an increased activation of MEK1/2, irrespective of the stimulation conditions. In contrast, KRAS K147E exhibited a tremendous increase in nucleotide dissociation generating a self-activating RAS protein that can act independently of upstream signals. As a consequence, levels of active KRAS K147E were strongly increased regardless of serum stimulation and similar to the oncogenic KRAS G12V . In spite of this, KRAS K147E downstream signalling did not reach the level triggered by oncogenic KRAS G12V , especially because KRAS K147E was downregulated by RASGAP and moreover exhibited a 2-fold lower affinity for RAF kinase. Here, our findings clearly emphasize that individual RAS mutations, despite being associated with comparable phenotypes of developmental disorders in patients, can cause remarkably diverse biochemical effects with a common outcome, namely a rather moderate gain-of-function.

Description: Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited disorder, which is caused by a pathological expansion of a polyglutamine (polyQ) tract in the coding region of the ATXN2 gene. Like other ataxias, SCA2 most overtly affects Purkinje cells (PCs) in the cerebellum. Using a transgenic mouse model expressing a full-length ATXN2 Q127 -complementary DNA under control of the Pcp2 promoter (a PC-specific promoter), we examined the time course of behavioral, morphologic, biochemical and physiological changes with particular attention to PC firing in the cerebellar slice. Although motor performance began to deteriorate at 8 weeks of age, reductions in PC number were not seen until after 12 weeks. Decreases in the PC firing frequency first showed at 6 weeks and paralleled deterioration of motor performance with progression of disease. Transcription changes in several PC-specific genes such as Calb1 and Pcp2 mirrored the time course of changes in PC physiology with calbindin-28 K changes showing the first small, but significant decreases at 4 weeks. These results emphasize that in this model of SCA2, physiological and behavioral phenotypes precede morphological changes by several weeks and provide a rationale for future studies examining the effects of restoration of firing frequency on motor function and prevention of future loss of PCs.

Description: Balancing selection has maintained human leukocyte antigen (HLA) allele diversity, but it is unclear whether this selection is symmetric (all heterozygotes are comparable and all homozygotes are comparable in terms of fitness) or asymmetric (distinct heterozygote genotypes display greater fitness than others). We tested the hypothesis that HLA is under asymmetric balancing selection in populations by estimating allelic branch lengths from genetic sequence data encoding peptide-binding domains. Significant deviations indicated changes in the ratio of terminal to internal branch lengths. Such deviations could arise even if no individual alleles present a strikingly altered branch length (e.g. if there is an overall distortion, with all or many terminal branches being longer than expected). DQ and DP loci were also analyzed as haplotypes. Using allele frequencies for 419 distinct populations in 10 geographical regions, we examined population differentiation in alleles within and between regions, and the relationship between allelic branch length and frequency. The strongest evidence for asymmetrical balancing selection was observed for HLA-DRB1 , HLA-B and HLA-DPA1 , with significant deviation ( P ≤ 1.1 x 10 –4 ) in about half of the populations. There were significant results at all loci except HLA-DQB1 / DQA1 . We observed moderate genetic variation within and between geographic regions, similar to the rest of the genome. Branch length was not correlated with allele frequency. In conclusion, sequence data suggest that balancing selection in HLA is asymmetric (some heterozygotes enjoy greater fitness than others). Because HLA polymorphism is crucial for pathogen resistance, this may manifest as a frequency-dependent selection with fluctuation in the fitness of specific heterozygotes over time.

Description: Birt–Hogg–Dubé syndrome (BHD) is a human cancer disorder caused by mutations in the tumor suppressor gene Folliculin ( FLCN ) with unknown biological functions. Here, we show that the Drosophila homolog of FLCN, dFLCN (a.k.a. dBHD ) localizes to the nucleolus and physically interacts with the 19S proteasomal ATPase, Rpt4, a nucleolar resident and known regulator of rRNA transcription. Downregulation of dFLCN resulted in an increase in nucleolar volume and upregulation of rRNA synthesis, whereas dFLCN overexpression reduced rRNA transcription and counteracted the effects of Rpt4 on rRNA production by preventing the association of Rpt4 with the rDNA locus. We further show that human FLCN exhibited evolutionarily conserved function and that Rpt4 knockdown inhibits the growth of FLCN-deficient human renal cancer cells in mouse xenografts. Our study suggests that FLCN functions as a tumor suppressor by negatively regulating rRNA synthesis.

Description: KitL, via its receptor cKit, supports primordial germ cell (PGC) growth, survival, migration and reprogramming to pluripotent embryonic germ cells (EGCs). However, the signaling downstream of KitL and its regulation in PGCs remain unclear. A constitutively activating mutation, cKit V558 , causes gain-of-function phenotypes in mast cells and intestines, and gastrointestinal stromal tumors (GISTs) when heterozygous. Unexpectedly, we find that PGC growth is not significantly affected in cKit V558 heterozygotes, whereas in homozygotes, increased apoptosis and inefficient migration lead to the depletion of PGCs. Through genetic studies, we reveal that this oncogenic cKit allele exhibits loss-of-function behavior in PGCs distinct from that in GIST development. Examination of downstream signaling in GISTs from cKit V558/+ mice confirmed hyperphosphorylation of AKT and ERK, but both remain unperturbed in cKit V558/+ PGCs and EGCs. In contrast, we find reduced activation of ERK1/2 and JNK1 in cKit V558 homozygous PGCs and EGCs. Inhibiting JNK, though not ERK1/2, increased apoptosis of wild-type PGCs, but did not further affect the already elevated apoptosis of cKit V558 / V558 PGCs. These results demonstrate a cell-context-dependent response to the cKit V558 mutation. We propose that AKT overload protection and JNK-mediated survival comprise PGC-specific mechanisms for regulating cKit signaling.

Description: TDP-43 is an evolutionarily conserved RNA-binding protein currently under intense investigation for its involvement in the molecular pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). TDP-43 is normally localized in the nucleus, but translocated to the cytoplasm in diseased neurons. The endogenous functions of TDP-43 in the nervous system remain poorly understood. Here, we show that the loss of Drosophila TDP-43 (dTDP-43) results in an increased production of sensory bristles and sensory organ precursor (SOP) cells on the notum of some but not all flies. The location of ectopic SOPs varies among mutant flies. The penetrance of this novel phenotype is dependent on the gender and sensitive to environmental influences. A similar SOP phenotype was also observed on the wing and in the embryos. Overexpression of dTDP-43 causes both loss and ectopic production of SOPs. Ectopic expression of ALS-associated mutant human TDP-43 (hTDP-43 M337V and hTDP-43 Q331K ) produces a less severe SOP phenotype than hTDP-43 WT , indicating a partial loss of function of mutant hTDP-43. In dTDP-43 mutants, miR-9a expression is significantly reduced. Genetic interaction studies further support the notion that dTDP-43 acts through miR-9a to control the precision of SOP specification. These findings reveal a novel role for endogenous TDP-43 in neuronal specification and suggest that the FTD/ALS-associated RNA-binding protein TDP-43 functions to ensure the robustness of genetic control programs.

Description: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most frequent known cause of late-onset Parkinson's disease (PD). To explore the therapeutic potential of small molecules targeting the LRRK2 kinase domain, we characterized two LRRK2 kinase inhibitors, TTT-3002 and LRRK2-IN1, for their effects against LRRK2 activity in vitro and in Caenorhabditis elegans models of LRRK2-linked neurodegeneration. TTT-3002 and LRRK2-IN1 potently inhibited in vitro kinase activity of LRRK2 wild-type and mutant proteins, attenuated phosphorylation of cellular LRRK2 and rescued neurotoxicity of mutant LRRK2 in transfected cells. To establish whether LRRK2 kinase inhibitors can mitigate pathogenesis caused by different mutations including G2019S and R1441C located within and outside of the LRRK2 kinase domain, respectively, we evaluated effects of TTT-3002 and LRRK2-IN1 against R1441C- and G2019S-induced neurodegeneration in C. elegans models. TTT-3002 and LRRK2-IN1 rescued the behavioral deficit characteristic of dopaminergic impairment in transgenic C. elegans expressing human R1441C- and G2019S-LRRK2. The inhibitors displayed nanomolar to low micromolar rescue potency when administered either pre-symptomatically or post-symptomatically, indicating both prevention and reversal of the dopaminergic deficit. The same treatments also led to long-lasting prevention and rescue of neurodegeneration. In contrast, TTT-3002 and LRRK2-IN1 were ineffective against the neurodegenerative phenotype in transgenic worms carrying the inhibitor-resistant A2016T mutation of LRRK2, suggesting that they elicit neuroprotective effects in vivo by targeting LRRK2 specifically. Our findings indicate that the LRRK2 kinase activity is critical for neurodegeneration caused by R1441C and G2019S mutations, suggesting that kinase inhibition of LRRK2 may represent a promising therapeutic strategy for PD.

Description: Mitochondrial DNA (mtDNA) mutations leading to the disruption of respiratory complex I (CI) have been shown to exhibit anti-tumorigenic effects, at variance with those impairing only the function but not the assembly of the complex, which appear to contribute positively to cancer development. Owing to the challenges in the analysis of the multi-copy mitochondrial genome, it is yet to be determined whether tumour-associated mtDNA lesions occur as somatic modifying factors or as germ-line predisposing elements. Here we investigated the whole mitochondrial genome sequence of 20 pituitary adenomas with oncocytic phenotype and identified pathogenic and/or novel mtDNA mutations in 60% of the cases. Using highly sensitive techniques, namely fluorescent PCR and allele-specific locked nucleic acid quantitative PCR, we identified the most likely somatic nature of these mutations in our sample set, since none of the mutations was detected in the corresponding blood tissue of the patients analysed. Furthermore, we have subjected a series of 48 pituitary adenomas to a high-resolution array comparative genomic hybridization analysis, which revealed that CI disruptive mutations, and the oncocytic phenotype, significantly correlate with low number of chromosomal aberrations in the nuclear genome. We conclude that CI disruptive mutations in pituitary adenomas are somatic modifiers of tumorigenesis most likely contributing not only to the development of oncocytic change, but also to a less aggressive tumour phenotype, as indicated by a stable karyotype.

Description: Functional loss of SMN1 causes proximal spinal muscular atrophy (SMA), the most common genetic condition accounting for infant lethality. Hence, the hypomorphic copy gene SMN2 is the only resource of functional SMN protein in SMA patients and influences SMA severity in a dose-dependent manner. Consequently, current therapeutic approaches focus on SMN2 . Histone deacetylase inhibitors (HDACi), such as the short chain fatty acid VPA (valproic acid), ameliorate the SMA phenotype by activating the SMN2 expression. By analyzing blood SMN2 expression in 16 VPA-treated SMA patients, about one-third of individuals were identified as positive responders presenting increased SMN2 transcript levels. In 66% of enrolled patients, a concordant response was detected in the respective fibroblasts. Most importantly, by taking the detour of reprograming SMA patients' fibroblasts, we showed that the VPA response was maintained even in GABAergic neurons derived from induced pluripotent stem cells (iPS) cells. Differential expression microarray analysis revealed a complete lack of response to VPA in non-responders, which was associated with an increased expression of the fatty acid translocase CD36. The pivotal role of CD36 as the cause of non-responsiveness was proven in various in vitro approaches. Most importantly, knockdown of CD36 in SMA fibroblasts converted non- into pos-responders. In summary, the concordant response from blood to the central nervous system (CNS) to VPA may allow selection of pos-responders prior to therapy. Increased CD36 expression accounts for VPA non-responsiveness. These findings may be essential not only for SMA but also for other diseases such as epilepsy or migraine frequently treated with VPA.

Description: Rett syndrome (RTT) is a neurodevelopmental disorder caused primarily by mutations of the X-linked MECP2 gene. Although the loss of MeCP2 function affects many neural systems, impairments of catecholaminergic function have been hypothesized to underlie several of the cardinal behavioral deficits of RTT patients and Mecp2-deficient mice. Although recent Mecp2 reactivation studies indicate that RTT may be a reversible condition, it remains unclear whether specifically preserving Mecp2 function within a specific system will be sufficient to convey beneficial effects. Here, we test whether the selective preservation of Mecp2 within catecholaminergic cells will improve the phenotype of Mecp2-deficient mice. Our results show that this targeted preservation of Mecp2 significantly improves the lifespan, phenotypic severity and cortical epileptiform discharge activity of both male and female Mecp2-deficient mice. Further, we found that the catecholaminergic preservation of Mecp2 also improves the ambulatory rate, rearing activity, motor coordination, anxiety and nest-building performances of Mecp2-deficient mice of each gender. Interestingly, our results also revealed a gender-specific improvement, as specific cortical and hippocampal electroencephalographic abnormalities were significantly improved in male, but not female, rescue mice. Collectively, these results support the role of the catecholaminergic system in the pathogenesis of RTT and provide proof-of-principle that restoring MeCP2 function within this specific system could represent a treatment strategy for RTT.

Description: Mutations in COL4A1 have been identified in families with hereditary small vessel disease of the brain presumably due to a dominant-negative mechanism. Here, we report on two novel mutations in COL4A1 in two families with porencephaly, intracerebral hemorrhage and severe white matter disease caused by haploinsufficiency. Two families with various clinical presentations of cerebral microangiopathy and autosomal dominant inheritance were examined. Clinical, neuroradiological and genetic investigations were performed. Electron microscopy of the skin was also performed. In one of the families, sequence analysis revealed a one base deletion, c.2085del, leading to a frameshift and a premature stopcodon, p.(Gly696fs). In the other family, a splice site mutation was identified, c.2194-1G〉A, which most likely leads to skipping of an exon with a frameshift and premature termination as a result. In fibroblasts of affected individuals from both the families, nonsense-mediated decay (NMD) of the mutant COL4A1 messenger RNAs (mRNAs) and a clear reduction of COL4A1 protein expression were demonstrated, indicating haploinsufficiency of COL4A1. Moreover, thickening of the capillary basement membrane in the skin was documented, similar to reports in patients with COL4A1 missense mutations. These findings suggest haploinsufficiency, a different mechanism from the commonly assumed dominant-negative effect, for COL4A1 mutations as a cause of (antenatal) intracerebral hemorrhage and white matter disease.

Description: Two pathways in the reaction of tert -butyl 3-oxo-1-oxa-8-azaspiro[4.5]decane-8-carboxylate with N,N -dimethylformamide dimethyl acetal Content Type Journal Article Category Short Communications Pages 1379-1381 DOI 10.1134/S1070428012100211 Authors A. I. Moskalenko, Lipetsk State Pedagogical University, ul. Lenina 42, Lipetsk, 398020 Russia V. I. Boev, Lipetsk State Pedagogical University, ul. Lenina 42, Lipetsk, 398020 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    C -Aryl- and C -carbamoylnitrones reacted with methyl 2-benzylidenecyclopropanecarboxylate in highly regioselective fashion to give the corresponding 1,3-dipolar cycloaddition products, substituted methyl 5-oxa-6-azaspiro[2.4]heptane-1-carboxylates as mixtures of two diastereoisomers. Content Type Journal Article Pages 1283-1288 DOI 10.1134/S1070428012100041 Authors A. P. Molchanov, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia T. Q. Tran, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Val-Val, Val-Thr, and Thr-Val dipeptides were synthesized using trifluoroacetyl protecting group. The optical rotations of the products were similar to those of samples synthesized using Boc protection, which indicated the absence of racemization in the course of introduction and removal of trifluoroacetyl protection. Content Type Journal Article Pages 1297-1301 DOI 10.1134/S1070428012100065 Authors Yu. M. Sorokina, Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, ul. Surganova 13, Minsk, 220072 Belarus A. A. Sladkova, Belarusian State University, Minsk, Belarus L. A. Popova, Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, ul. Surganova 13, Minsk, 220072 Belarus O. I. Shadyro, Belarusian State University, Minsk, Belarus V. A. Knizhnikov, Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, ul. Surganova 13, Minsk, 220072 Belarus Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description: [3 + 3]-nucleophilic addition of acyclic enamino ketones to dimethyl 1-aryl-4,5-dioxo-4,5-dihydro-1 H -pyrrole-2,3-dicarboxylates Content Type Journal Article Category Short Communications Pages 1377-1378 DOI 10.1134/S107042801210020X Authors P. S. Silaichev, Institute of Natural Sciences, Perm State National Research University, ul. Genkelya 4, Perm, 614990 Russia M. A. Chudinova, Perm State National Research University, Perm, Russia A. N. Maslivets, Institute of Natural Sciences, Perm State National Research University, ul. Genkelya 4, Perm, 614990 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description: Selective synthesis of 3-[1-(organylsulfanyl)ethyl]- and 3-[2-(organylsulfanyl)ethyl]-5-chloro-1 H -pyrazoles Content Type Journal Article Category Short Communications Pages 1388-1389 DOI 10.1134/S1070428012100259 Authors D. O. Samultsev, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia E. V. Rudyakova, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia G. G. Levkovskaya, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Substituted 5-oxa-6-azaspiro[2.4]heptane-1,2-dicarboxylic acid esters synthesized by reaction of nitrones with dimethyl 3-methylidenecyclopropane-1,2-dicarboxylate were reduced with lithium tetrahydridoaluminate to the corresponding bis(hydroxymethyl)cyclopropanes. Alkaline hydrolysis of the title compounds gave substituted cyclopropane-1,2-dicarboxylic acids. In both cases, the 5-oxa-6-azaspiro[2.4]heptane fragment remained intact. Content Type Journal Article Pages 1323-1325 DOI 10.1134/S1070428012100107 Authors A. P. Molchanov, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia T. Q. Tran, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Peroxide products generated by ozonolysis of non-1-ene, 3-carene, stereoisomeric α-pinenes, (−)-limonene, and castor oil were subjected to transformations by the action of semicarbazide and hydrazine-1,2-dicarboxamide in methanol. Content Type Journal Article Pages 1272-1276 DOI 10.1134/S1070428012100028 Authors G. Yu. Ishmuratov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Yu. V. Legostaeva, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia L. P. Botsman, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia G. V. Nasibullina, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia L. R. Garifullina, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia R. R. Muslukhov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia G. A. Tolstikov, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Methyl 1-aryl-3-cinnamoyl-4,5-dioxo-4,5-dihydro-1 H -pyrrole-2-carboxylates reacted with 4-benzylamino- and 4-arylaminopent-3-en-2-ones to give 1-aryl-7-benzyl- and 1,7-diaryl-9-acetyl-4-cinnamoyl-3-hydroxy-8-methyl-1,7-diazaspiro[4.4]nona-3,8-diene-2,6-diones. The crystalline and molecular structures of 9-acetyl-4-cinnamoyl-3-hydroxy-1-(4-methoxyphenyl)-8-methyl-7-phenyl-1,7-diazaspiro[4.4]nona-3,8-diene-2,6-dione were studied by X-ray analysis. Content Type Journal Article Pages 1329-1332 DOI 10.1134/S1070428012100120 Authors P. S. Silaichev, Institute of Natural Sciences, Perm State National Research University, ul. Genkelya 4, Perm, 614990 Russia V. O. Filimonov, Perm State National Research University, Perm, Russia P. A. Slepukhin, Postovskii Institute of Organic Synthesis, Ural Division, Russian Academy of Sciences, ul. Akademicheskaya/S. Kovalevskoi 22/20, Yekaterinburg, 620990 Russia A. N. Maslivets, Institute of Natural Sciences, Perm State National Research University, ul. Genkelya 4, Perm, 614990 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    2-Perfluoroalkanoylcyclopentane-1,3-diones were synthesized for the first time by acylation of cyclopentane-1,3-dione with perfluorocarboxylic acids in the presence of 1,1′-carbonyldiimidazole or with perfluorocarboxylic anhydrides in the presence of imidazole. 2-Perfluoroalkanoylcyclopentane-1,3-diones were selectively reduced to 2-(1-hydroxyperfluoroalkyl)cyclopentane-1,3-diones by the action of triethylsilane in trifluoroacetic acid in the presence of a catalytic amount of lithium perchlorate. Treatment of the title compounds with oxalyl chloride and subsequent reaction with 2 equiv of primary amine (4-fluoroaniline, 4-fluorobenzylamine, 3,4-difluoroaniline, 3-trifluoromethylbenzylamine) gave the corresponding 3-arylamino-2-perfluoroalkanoylcyclopent-2-en-1-ones. Content Type Journal Article Pages 1277-1282 DOI 10.1134/S107042801210003X Authors T. S. Khlebnikova, Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus Yu. A. Piven’, Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus V. G. Isakova, Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus F. A. Lakhvich, Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, ul. Akademika Kuprevicha 5/2, Minsk, 220141 Belarus Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    A number of new alkoxy- and phenylsulfanyl-substituted 1,1-dihalospiro[2.2]pentanes bearing different halogen atoms were synthesized. 1,1-Dihalo-4- tert -butoxyspiro[2.2]pentanes reacted with methyllithium at −55 to −10°C to give exclusively 1- tert -butoxy-2-vinylidenecyclopropane. The reaction of 1-bromo-1-fluoro-4-phenylsulfanylspiro[2,2]pentane with methyllithium resulted in replacement of the fluorine atom by methyl group. Content Type Journal Article Pages 1265-1271 DOI 10.1134/S1070428012100016 Authors K. N. Sedenkova, Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia E. B. Averina, Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia I. S. Borisov, Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia Yu. K. Grishin, Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia V. B. Rybakov, Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia T. S. Kuznetsova, Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia N. S. Zefirov, Faculty of Chemistry, Moscow State University, Leninskie gory 1, Moscow, 119991 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    The equilibrium in the reversible rearrangement of 5-methyl-1,2,3-thiadiazole-4-carbothioamides into 5-amino-4-thioacetyl-1,2,3-thiadiazoles is displaced toward the former, and polar solvents favor increased fraction of the thioketone. Content Type Journal Article Pages 1333-1336 DOI 10.1134/S1070428012100132 Authors P. E. Prokhorova, Yeltsin Ural Federal University, ul. Mira 19, Yekaterinburg, 620002 Russia T. A. Kalinina, Yeltsin Ural Federal University, ul. Mira 19, Yekaterinburg, 620002 Russia T. V. Glukhareva, Yeltsin Ural Federal University, ul. Mira 19, Yekaterinburg, 620002 Russia Yu. Yu. Morzherin, Yeltsin Ural Federal University, ul. Mira 19, Yekaterinburg, 620002 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Conformational analysis of bis(2-phenylalkyl)phosphine selenides was performed by the dipole moment method and quantum-chemical calculations. Bis(2-phenylpropyl)phosphine selenide was found to exist as a mixture of several conformers, the most energetically favorable of which being characterized by gauche (non-eclipsed) orientation of the P=Se and bonds. Content Type Journal Article Pages 1320-1322 DOI 10.1134/S1070428012100090 Authors Ya. A. Vereshchagina, Kazan (Volga Region) Federal University, ul. Kremlevskaya 18, Kazan, 420008 Tatarstan, Russia D. V. Chachkov, Kazan Branch, Joint Supercomputer Center of the Russian Academy of Sciences, Kazan, Tatarstan, Russia A. Z. Alimova, Kazan (Volga Region) Federal University, ul. Kremlevskaya 18, Kazan, 420008 Tatarstan, Russia E. A. Ishmaeva, Kazan (Volga Region) Federal University, ul. Kremlevskaya 18, Kazan, 420008 Tatarstan, Russia S. F. Malysheva, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    1,3- Alternate and cone stereoisomers of tetrathiacalix[4]arene and 4- tert -butyltetrathiacalix[4]arene functionalized by carbohydrazide groups reacted with 3,5-di- tert -butyl-4-hydroxybenzaldehyde to give the corresponding hydrazones having sterically hindered phenol fragments. Content Type Journal Article Pages 1360-1365 DOI 10.1134/S107042801210017X Authors S. N. Podyachev, Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences, ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia T. A. Barsukova, Kazan National Research Technological University, Kazan, Tatarstan, Russia S. V. Bukharov, Kazan National Research Technological University, Kazan, Tatarstan, Russia V. V. Syakaev, Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences, ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia S. N. Sudakova, Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences, ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia G. N. Nugumanova, Kazan National Research Technological University, Kazan, Tatarstan, Russia A. I. Konovalov, Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences, ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Three synthetic approaches to triterpene-spermidine conjugate coupled at the C 3 atom have been tested. The best yield was obtained by reductive amination of betulonic acid methyl ester with spermidine. Content Type Journal Article Pages 1366-1369 DOI 10.1134/S1070428012100181 Authors O. B. Kazakova, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia G. V. Giniyatullina, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia N. I. Medvedeva, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia G. A. Tolstikov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description: Synthesis of 1-(arylsulfonyl)pyrazolo[1,5- a ]pyridines Content Type Journal Article Category Short Communications Pages 1382-1383 DOI 10.1134/S1070428012100223 Authors S. A. Mamedov, Guliyev Institute of Chemistry of Additives, National Academy of Sciences of Azerbaijan, pr. G. Dzhavida 29, Baku, Az1143 Azerbaijan L. M. Shakhgel’dieva, Guliyev Institute of Chemistry of Additives, National Academy of Sciences of Azerbaijan, pr. G. Dzhavida 29, Baku, Az1143 Azerbaijan S. I. Mamedova, Guliyev Institute of Chemistry of Additives, National Academy of Sciences of Azerbaijan, pr. G. Dzhavida 29, Baku, Az1143 Azerbaijan N. P. Ladokhina, Guliyev Institute of Chemistry of Additives, National Academy of Sciences of Azerbaijan, pr. G. Dzhavida 29, Baku, Az1143 Azerbaijan I. Sh. Guseinov, Guliyev Institute of Chemistry of Additives, National Academy of Sciences of Azerbaijan, pr. G. Dzhavida 29, Baku, Az1143 Azerbaijan Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Optimal conditions were found for induced hydroxyhalogenation of cyclic dienes (tetrahydroindene, 4-vinylcyclohexene and 5-vinyl- and 5-cyclohexenylbicyclo[2.2.1]hept-2-enes) in the system [MHlg-HA or HHlg]-H 2 O 2 (or NaClO). Dehydrohalogenation of the chloro- and bromohydrins thus obtained with powdered potassium carbonate gave the corresponding diepoxy derivatives, and their hydrolysis led to mixtures of stereoisomeric tetrahydric alcohols. Content Type Journal Article Pages 1302-1308 DOI 10.1134/S1070428012100077 Authors Kh. M. Alimardanov, Mamedaliev Institute of Petrochemical Processes, National Academy of Sciences of Azerbaijan, pr. Khodzhaly 30, Baku, AZ 1025 Azerbaijan O. A. Sadygov, Mamedaliev Institute of Petrochemical Processes, National Academy of Sciences of Azerbaijan, pr. Khodzhaly 30, Baku, AZ 1025 Azerbaijan N. I. Garibov, Mamedaliev Institute of Petrochemical Processes, National Academy of Sciences of Azerbaijan, pr. Khodzhaly 30, Baku, AZ 1025 Azerbaijan M. Ya. Abdullaeva, Mamedaliev Institute of Petrochemical Processes, National Academy of Sciences of Azerbaijan, pr. Khodzhaly 30, Baku, AZ 1025 Azerbaijan Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    New N -aryl(phenoxy, benzylidene)acetyl-1,4-benzoquinone monoimines were synthesized by reaction of aminophenols with arylacetyl, phenoxyacetyl, and cinnamoyl chlorides in dimethylformamide-acetic acid (1: 3) in the presence of anhydrous sodium acetate. Structural parameters of the products and their probable biological activity were determined. Content Type Journal Article Pages 1309-1319 DOI 10.1134/S1070428012100089 Authors A. P. Avdeenko, Donbass State Engineering Academy, ul. Shkadinova 72, Kramatorsk, 84313 Ukraine S. A. Konovalova, Donbass State Engineering Academy, ul. Shkadinova 72, Kramatorsk, 84313 Ukraine V. M. Vasil’eva, Donbass State Engineering Academy, ul. Shkadinova 72, Kramatorsk, 84313 Ukraine O. V. Shishkin, Institute of Single Crystals, National Academy of Sciences of Ukraine, Kharkov, Ukraine G. V. Palamarchuk, Institute of Single Crystals, National Academy of Sciences of Ukraine, Kharkov, Ukraine V. N. Baumer, Institute of Single Crystals, National Academy of Sciences of Ukraine, Kharkov, Ukraine Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Amino acetals of the general formula MeCH(OR)(OXNH 2 ) (R = Et, Bu, X = CH 2 CH 2 , CH 2 CH 2 CH 2 , CH 2 CMe 2 ) were synthesized in 53–91% yield by acid-catalyzed reaction of N -(2-hydroxyethyl)-, N -(3-hydroxypropyl)-, and N -(2-hydroxy-1,1-dimethylethyl)-2,2,2-trifluoroacetamides with vinyl ethers, followed by removal of the trifluoroacetyl protection by alkaline hydrolysis. Content Type Journal Article Pages 1289-1296 DOI 10.1134/S1070428012100053 Authors N. A. Lobanova, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia V. K. Stankevich, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia B. F. Kukharev, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Conformational analysis of 4-methyl-2-trimethylsiloxy-1,3,2-dioxaphosphinane was performed by the dipole moment method and quantum-chemical calculations. The 1,3,2-dioxaphosphinane heteroring was found to adopt a chair conformation with equatorial orientation of the 4-methyl group and axial orientation of the irregular trimethylsiloxy substituent. The conformational equilibrium involves non-eclipsed gauche and trans conformers (the latter prevailing) interconvertible through rotation about the exocyclic P-O bond. Content Type Journal Article Pages 1326-1328 DOI 10.1134/S1070428012100119 Authors Ya. A. Vereshchagina, Kazan (Volga Region) Federal University, ul. Kremlevskaya 18, Kazan, 420008 Tatarstan, Russia E. A. Ishmaeva, Kazan (Volga Region) Federal University, ul. Kremlevskaya 18, Kazan, 420008 Tatarstan, Russia D. V. Chachkov, Kazan Branch, Joint Supercomputer Center of the Russian Academy of Sciences, Kazan, Tatarstan, Russia A. Z. Alimova, Kazan (Volga Region) Federal University, ul. Kremlevskaya 18, Kazan, 420008 Tatarstan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Oxidation of dipterocarpol and its derivatives with ozone gave compounds containing lactone, lactol, alkoxytetrahydrofuran, aldehyde, and methyl ketone fragments in the side chain, as well as 1,2,4-trioxolane fragment in the A ring. The molecular and crystalline structures of dipterocarpol were determined by X-ray analysis. Content Type Journal Article Pages 1370-1376 DOI 10.1134/S1070428012100193 Authors I. E. Smirnova, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia H. Do Thi Thu, Institute of Chemistry, Vietnam Academy of Sciences and Technologies, Hanoi, Vietnam O. B. Kazakova, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia G. A. Tolstikov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia O. S. Kukovinets, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia A. N. Lobov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia K. Yu. Suponitskii, Nesmeyanov Institute of Organometallic Compounds, Russian Academy of Sciences, ul. Vavilova 28, Moscow, 119991 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    Adenine complexes with nitrosonium ion have been studied by the RI-MP2/L1 quantum-chemical method. Addition of nitrosonium ion to adenine tautomers produces a set of nitrosonium complexes of different types (1η–3η). n -Complexes involving NO + coordination to nitrogen atoms are more energetically favorable than π-complexes. The global minimum on the potential energy surface is occupied by the complex of 7 H -adenine tautomer with nitrosonium ion coordinated at the N 3 atom. Content Type Journal Article Pages 1337-1344 DOI 10.1134/S1070428012100144 Authors R. V. Andreev, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia G. I. Borodkin, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia V. G. Shubin, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description: Synthesis of 2,6-diazatricyclododecanes from 2-hydroxy-3,5-dinitropyridine Content Type Journal Article Category Short Communications Pages 1384-1385 DOI 10.1134/S1070428012100235 Authors E. V. Morozova, Tolstoy Tula State Pedagogical University, pr. Lenina 125, Tula, 300026 Russia I. E. Yakunina, Tolstoy Tula State Pedagogical University, pr. Lenina 125, Tula, 300026 Russia I. V. Blokhin, Tula State University, Tula, Russia I. V. Shakhkel’dyan, Tolstoy Tula State Pedagogical University, pr. Lenina 125, Tula, 300026 Russia Yu. M. Atroshchenko, Tolstoy Tula State Pedagogical University, pr. Lenina 125, Tula, 300026 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    A procedure has been proposed for the synthesis of monoazacrown ethers by reaction of N -benzyldiethanolamine with oligo(ethylene glycol) bis- p -toluenesulfonates in a two-phase system aromatic hydrocarbon-50% aqueous alkali, followed by removal of the benzyl group by catalytic hydrogenolysis. The maximal yields of N -benzylaza-12-crown-4, -18-crown-6, and -21-crown-7 were achieved by adding 4–10 equiv of LiCl, BaBr 2 , and CsCl, respectively, to the reaction mixture, which probably indicated template effect. Content Type Journal Article Pages 1345-1352 DOI 10.1134/S1070428012100156 Authors N. G. Luk’yanenko, Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine S. S. Basok, Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine E. Yu. Kulygina, Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine T. Yu. Bogashchenko, Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine I. S. Yakovenko, Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description:    New crownophanes containing 2,7-dioxyfluorenone and 4,4′-dioxystilbene fragments linked through di-, three, tetra-, and pentaethylene glycol linkers were synthesized. The formation of pseudorotaxanetype host-guest complexes in reactions of these crownophanes with 1,1′-dimethyl-4,4′-bipyridinium dication was detected by fast atom bombardment mass spectrometry, 1 H NMR, and electron spectroscopy. Content Type Journal Article Pages 1353-1359 DOI 10.1134/S1070428012100168 Authors A. Yu. Lyapunov, Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine T. I. Kirichenko, Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine E. Yu. Kulygina, Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine N. G. Luk’yanenko, Bogatskii Physicochemical Institute, National Academy of Sciences of Ukraine, Lyustdorfskaya doroga 86, Odessa, 65080 Ukraine Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 10

Description: Although biallelic mutations in non-collagen genes account for 〈10% of individuals with osteogenesis imperfecta, the characterization of these genes has identified new pathways and potential interventions that could benefit even those with mutations in type I collagen genes. We identified mutations in FKBP10 , which encodes the 65 kDa prolyl cis–trans isomerase, FKBP65, in 38 members of 21 families with OI. These include 10 families from the Samoan Islands who share a founder mutation. Of the mutations, three are missense; the remainder either introduce premature termination codons or create frameshifts both of which result in mRNA instability. In four families missense mutations result in loss of most of the protein. The clinical effects of these mutations are short stature, a high incidence of joint contractures at birth and progressive scoliosis and fractures, but there is remarkable variability in phenotype even within families. The loss of the activity of FKBP65 has several effects: type I procollagen secretion is slightly delayed, the stabilization of the intact trimer is incomplete and there is diminished hydroxylation of the telopeptide lysyl residues involved in intermolecular cross-link formation in bone. The phenotype overlaps with that seen with mutations in PLOD2 (Bruck syndrome II), which encodes LH2, the enzyme that hydroxylates the telopeptide lysyl residues. These findings define a set of genes, FKBP10 , PLOD2 and SERPINH1 , that act during procollagen maturation to contribute to molecular stability and post-translational modification of type I procollagen, without which bone mass and quality are abnormal and fractures and contractures result.

Description: The GUCY2D gene encodes retinal membrane guanylyl cyclase (RetGC1), a key component of the phototransduction machinery in photoreceptors. Mutations in GUCY2D cause Leber congenital amaurosis type 1 (LCA1), an autosomal recessive human retinal blinding disease. The effects of RetGC1 deficiency on human rod and cone photoreceptor structure and function are currently unknown. To move LCA1 closer to clinical trials, we characterized a cohort of patients (ages 6 months—37 years) with GUCY2D mutations. In vivo analyses of retinal architecture indicated intact rod photoreceptors in all patients but abnormalities in foveal cones. By functional phenotype, there were patients with and those without detectable cone vision. Rod vision could be retained and did not correlate with the extent of cone vision or age. In patients without cone vision, rod vision functioned unsaturated under bright ambient illumination. In vitro analyses of the mutant alleles showed that in addition to the major truncation of the essential catalytic domain in RetGC1, some missense mutations in LCA1 patients result in a severe loss of function by inactivating its catalytic activity and/or ability to interact with the activator proteins, GCAPs. The differences in rod sensitivities among patients were not explained by the biochemical properties of the mutants. However, the RetGC1 mutant alleles with remaining biochemical activity in vitro were associated with retained cone vision in vivo . We postulate a relationship between the level of RetGC1 activity and the degree of cone vision abnormality, and argue for cone function being the efficacy outcome in clinical trials of gene augmentation therapy in LCA1.

Description: Male patients with Peutz–Jeghers syndrome (PJS) have defective spermatogenesis and are at increased risk of developing Sertoli cell tumors. Mutations in the Liver Kinase B1 ( LKB1/STK11) gene are associated with the pathogenesis of PJS and have been identified in non-PJS patients with sporadic testicular cancers. The mechanisms controlled by LKB1 signaling in Sertoli cell functions and testicular biology have not been described. We have conditionally deleted the Lkb1 gene ( Lkb1 cko ) in somatic testicular cells to define the molecular mechanisms involved in the development of the testicular phenotype observed in PJS patients. Focal vacuolization in some of the seminiferous tubules was observed in 4-week-old mutant testes but germ cell development appeared to be normal. However, similar to PJS patients, we observed progressive germ cell loss and Sertoli cell only tubules in Lkb1 cko testes from mice older than 10 weeks, accompanied by defects in Sertoli cell polarity and testicular junctional complexes and decreased activation of the MAP/microtubule affinity regulating and focal adhesion kinases. Suppression of AMP kinase and activation of mammalian target of rapamycin (mTOR) signaling were also observed in Lkb1 cko testes. Loss of Tsc1 or Tsc2 copies the progressive Lkb1 cko phenotype, suggesting that dysregulated activation of mTOR contributes to the pathogenesis of the Lkb1 cko testicular phenotype. Pten cko mice had a normal testicular phenotype, which could be explained by the comparative lack of mTOR activation detected. These studies describe the importance of LKB1 signaling in testicular biology and the possible molecular mechanisms driving the pathogenesis of the testicular defects observed in PJS patients.

Description: The human X-linked macrosatellite DXZ4 is a large tandem repeat located at Xq23 that is packaged into heterochromatin on the male X chromosome and female active X chromosome and, in response to X chromosome, inactivation is organized into euchromatin bound by the insulator protein CCCTC-binding factor (CTCF) on the inactive X chromosome (Xi). The purpose served by this unusual epigenetic regulation is unclear, but suggests a Xi-specific gain of function for DXZ4. Other less extensive bands of euchromatin can be observed on the Xi, but the identity of the underlying DNA sequences is unknown. Here, we report the identification of two novel human X-linked tandem repeats, located 58 Mb proximal and 16 Mb distal to the macrosatellite DXZ4. Both tandem repeats are entirely contained within the transcriptional unit of novel spliced transcripts. Like DXZ4, the tandem repeats are packaged into Xi-specific CTCF-bound euchromatin. These sequences undergo frequent CTCF-dependent interactions with DXZ4 on the Xi, implicating DXZ4 as an epigenetically regulated Xi-specific structural element and providing the first putative functional attribute of a macrosatellite in the human genome.

Description: The apolipoprotein E ( APOE ) genotype is the major genetic risk factor for Alzheimer's disease (AD). We have access to cerebrospinal fluid (CSF) and plasma APOE protein levels from 641 individuals and genome-wide genotyped data from 570 of these samples. The aim of this study was to test whether CSF or plasma APOE levels could be a useful endophenotype for AD and to identify genetic variants associated with APOE levels. We found that CSF ( P = 8.15 x 10 –4 ) but not plasma ( P = 0.071) APOE protein levels are significantly associated with CSF Aβ 42 levels. We used Mendelian randomization and genetic variants as instrumental variables to confirm that the association of CSF APOE with CSF Aβ 42 levels and clinical dementia rating (CDR) is not because of a reverse causation or confounding effect. In addition the association of CSF APOE with Aβ 42 levels was independent of the APOE 4 genotype, suggesting that APOE levels in CSF may be a useful endophenotype for AD. We performed a genome-wide association study to identify genetic variants associated with CSF APOE levels: the APOE 4 genotype was the strongest single-genetic factor associated with CSF APOE protein levels ( P = 6.9 x 10 –13 ). In aggregate, the Illumina chip single nucleotide polymorphisms explain 72% of the variability in CSF APOE protein levels, whereas the APOE 4 genotype alone explains 8% of the variability. No other genetic variant reached the genome-wide significance threshold, but nine additional variants exhibited a P -value 〈10 –6 . Pathway mining analysis indicated that these nine additional loci are involved in lipid metabolism ( P = 4.49 x 10 –9 ).

Description:    Treatment of ethyl 7-amino-3- tert -butyl-4-oxo-4,6-dihydropyrazolo[5,1- c ][1,2,4]triazine-8-carboxylate with P 2 S 5 in pyridine gave ethyl 7-amino-3- tert -butyl-4-thioxo-4,6-dihydropyrazolo[5,1- c ][1,2,4]triazine-8-carboxylate which was subjected to acylation, decarboxylation, and hydrazinolysis. Content Type Journal Article Pages 1226-1228 DOI 10.1134/S1070428012090138 Authors L. M. Mironovich, Southwest State University, ul. 50 let Oktyabrya 94, Kursk, 305040 Russia M. V. Kostina, Southwest State University, ul. 50 let Oktyabrya 94, Kursk, 305040 Russia A. V. Bozhok, Southwest State University, ul. 50 let Oktyabrya 94, Kursk, 305040 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description: Two methods for generation of aroyl(quinoxalin-2-yl)ketene Content Type Journal Article Category Short Communications Pages 1261-1262 DOI 10.1134/S1070428012090229 Authors P. S. Silaichev, Institute of Natural Science, Perm State National Research University, ul. Genkelya 4, Perm, 614990 Russia A. N. Maslivets, Institute of Natural Science, Perm State National Research University, ul. Genkelya 4, Perm, 614990 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description: Unusual reaction of adamantane-1-carboxylic acid and adamantane-1-carbonyl chloride with acetonitrile and carbon tetrachloride in the presence of VO(acac) 2 Content Type Journal Article Category Short Communications Pages 1252-1253 DOI 10.1134/S1070428012090187 Authors R. I. Khusnutdinov, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia N. A. Shchadneva, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia Yu. Yu. Mayakova, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia U. M. Dzhemilev, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description: Synthesis of some oxygen-containing heterocycles from methyl 3-hydroxyphenylcarbamate Content Type Journal Article Category Short Communications Pages 1254-1256 DOI 10.1134/S1070428012090199 Authors A. V. Velikorodov, Astrakhan State University, pl. Shaumyana 1, Astrakhan, 414000 Russia V. A. Ionova, Astrakhan State University, pl. Shaumyana 1, Astrakhan, 414000 Russia S. I. Temirbulatova, Astrakhan State University, pl. Shaumyana 1, Astrakhan, 414000 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    5-Substituted furan-2(3 H )-ones and 1-phenyl-1 H -pyrrol-2(3 H )-ones reacted with diazonium salts derived from substituted anilines and 1 H -1,2,4-triazol-5-amine to give azo coupling products at the methylene group in the heteroring. The products were found to exist as hydrazone tautomers. Content Type Journal Article Pages 1229-1232 DOI 10.1134/S107042801209014X Authors D. N. Gavkus, Chernyshevskii Saratov State University, ul. Astrakhanskaya 83, Saratov, 410012 Russia O. A. Maiorova, Chernyshevskii Saratov State University, ul. Astrakhanskaya 83, Saratov, 410012 Russia M. Yu. Borisov, Chernyshevskii Saratov State University, ul. Astrakhanskaya 83, Saratov, 410012 Russia A. Yu. Egorova, Chernyshevskii Saratov State University, ul. Astrakhanskaya 83, Saratov, 410012 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description: Synthesis of dispiro hetero analogs of pyrrolizidine alkaloids Content Type Journal Article Category Short Communications Pages 1257-1258 DOI 10.1134/S1070428012090205 Authors V. V. Konovalova, Institute of Technical Chemistry, Ural Division, Russian Academy of Sciences, Perm, Russia Yu. V. Shklyaev, Institute of Technical Chemistry, Ural Division, Russian Academy of Sciences, Perm, Russia A. N. Maslivets, Perm State University, ul. Bukireva 15, Perm, 614990 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    Oxidation of 3-methyl-2-sulfanylquinazolin-4(3 H )-one with chlorine dioxide under different conditions gave 2,2′-disulfanediylbis[3-methylquinazolin-4(3 H )-one], 3-methyl-4-oxo-3,4-dihydroquinazoline-2-sulfonic acid, 3-methylquinazoline-2,4(1 H ,3 H )-dione, 6-chloro-3-methylquinazoline-2,4(1 H ,3 H )-dione, and N , N -diethyl-3-methyl-4-oxo-3,4-dihydroquinazoline-2-sulfonamide. Content Type Journal Article Pages 1222-1225 DOI 10.1134/S1070428012090126 Authors O. M. Lezina, Institute of Chemistry, Komi Research Center, Ural Division, Russian Academy of Sciences, ul. Pervomaiskaya 48, Syktyvkar, 167982 Russia S. A. Rubtsova, Institute of Chemistry, Komi Research Center, Ural Division, Russian Academy of Sciences, ul. Pervomaiskaya 48, Syktyvkar, 167982 Russia V. A. Polukeev, Vekton Closed Corporation, St. Petersburg, Russia A. V. Kutchin, Institute of Chemistry, Komi Research Center, Ural Division, Russian Academy of Sciences, ul. Pervomaiskaya 48, Syktyvkar, 167982 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    The activation parameters for the reactions of 4-nitrophenyl acetate with 4-chlorophenol and benzenethiol in the presence of potassium carbonate in dimethylformamide were determined. Depending on the substrate structure, the enthalpy and entropy of activation decrease in going from 4-nitrophenyl acetate to 4-nitrophenyl benzoate, while the Gibbs energy of activation increases. Content Type Journal Article Pages 1197-1199 DOI 10.1134/S1070428012090084 Authors I. A. Os’kina, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    Mannich reactions of ethyl 1-aryl-2,2,2-trifluoroethylidenecarbamates and ureas with acetone in the presence of L-proline gave 1-aryl-3-oxo-1-(trifluoromethyl)butylcarbamates and ureas with an enantiomeric excess of 24–54%. Content Type Journal Article Pages 1187-1190 DOI 10.1134/S1070428012090060 Authors N. M. Golovach, Institute of Organic Chemistry, National Academy of Sciences of Ukraine, ul. Murmanskaya 5, Kiev, 02660 Ukraine V. N. Tkachuk, Institute of Organic Chemistry, National Academy of Sciences of Ukraine, ul. Murmanskaya 5, Kiev, 02660 Ukraine V. A. Sukach, Institute of Organic Chemistry, National Academy of Sciences of Ukraine, ul. Murmanskaya 5, Kiev, 02660 Ukraine M. V. Vovk, Institute of Organic Chemistry, National Academy of Sciences of Ukraine, ul. Murmanskaya 5, Kiev, 02660 Ukraine Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    Reactions of some 1,5-diketones with 2-aminobenzyl alcohol and 2-aminomethylaniline follow double cyclization scheme with formation of pyridobenzoxazine and pyridoquinazoline derivatives, respectively. Oxidative coupling of the cyclization products with CH acids occurs at the 4-position of the pyridine ring. Content Type Journal Article Pages 1180-1186 DOI 10.1134/S1070428012090059 Authors O. Yu. Slabko, Far East Federal University, ul. Oktyabr’skaya 27, Vladivostok, 690600 Russia A. V. Kachanov, Far East Federal University, ul. Oktyabr’skaya 27, Vladivostok, 690600 Russia V. A. Kaminskii, Far East Federal University, ul. Oktyabr’skaya 27, Vladivostok, 690600 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    Copper compounds of the general formula CuX n (X = Cl, Br, I, acac, OAc, C 7 H 4 O 3 , C 7 H 5 O 2 ; n = 1, 2) activated by carbon tetrabromide catalyzed intermolecular dehydration of primary and secondary alcohols with formation of the corresponding ethers. Content Type Journal Article Pages 1191-1196 DOI 10.1134/S1070428012090072 Authors R. I. Khusnutdinov, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia A. R. Bayguzina, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia L. I. Gimaletdinova, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia U. M. Dzhemilev, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    2-(1-Iodoethyl)-3,5-dimethyl-1-(4-methylphenylsulfonyl)-2,3-dihydro-1 H -indole reacted with pyridine, piperidine, N -alkylpiperidines, and dimethylformamide to give dehydrohalogenation and halogen substitution products whose ratio depended on the reagent structure. Heating of 2-(1-iodoethyl)-3,5-dimethyl-1-methylsulfonyl-2,3-dihydro-1 H -indole with piperidine resulted in the formation of only dehydroiodination products. Content Type Journal Article Pages 1200-1209 DOI 10.1134/S1070428012090096 Authors G. G. Mazgarova, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia A. M. Absalyamova, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia R. R. Gataullin, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    Previously unknown seven-membered lactones, (1 R ,1′ R ,5 S ,5′ S )-5,5′-oxybis(1,8,8-trimethyl-2-oxabicyclo[3.2.1]octan-3-one), 2,2-dimethyl-1,6-dioxaspiro[2.6]nonan-7-one, 4-(1-hydroxy-1-methylethyl)-7-methyloxepan-2-one, and (4 R ,4′ R ,7 S ,7′ S )-4,4′-[oxybis(propane-2,2-diyl)]bis(7-methyloxepan-2-one), were synthesized by the Baeyer-Villiger reaction using Caro’s acid as a result of oxidative and skeletal transformations of bicyclic monoterpene ketones, (+)-camphor, (+)-nopinone, and (−)-isocaranone. Content Type Journal Article Pages 1210-1215 DOI 10.1134/S1070428012090102 Authors G. Yu. Ishmuratov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia V. A. Vydrina, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia M. P. Yakovleva, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Yu. A. Galkina, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia I. F. Lobko, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia R. R. Muslukhov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia E. M. Vyrypaev, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia A. G. Tolstikov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    Furfuryl and tetrahydrofurfuryl vinyl ethers reacted with various alcohols under mild conditions (20–25°C, 1–3 h, 1 wt % of CF 3 COOH) with high chemo- and regioselectivity to give the corresponding Markovnikov adducts at the vinyl group in up to 93% yield. Content Type Journal Article Pages 1162-1167 DOI 10.1134/S1070428012090023 Authors L. A. Oparina, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia O. V. Vysotskaya, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia A. V. Stepanov, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia N. K. Gusarova, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia B. A. Trofimov, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    Bromomethyl cyclopent-1-enyl sulfone and bromomethyl cyclohex-1-enyl sulfone reacted with dimethyl malonate and malononitrile sodium salts in THF at 20–50°C to give products of Michael-induced Ramberg-Bäcklund reaction, functionalized derivatives of methylidenecyclopentane and methylidenecyclohexane. Reactions of bromomethyl hex-1-en-1-yl sulfone and bromomethyl hept-1-en-1-yl sulfones with the same sodium enolates followed the Michael-induced ring closure pattern with formation of tetrahydrothiophene 1,1-dioxide derivatives containing allylmalonic acid derivatives as impurities. Factors responsible for the different reaction pathways of cyclic and acyclic bromomethyl sulfones are discussed. Content Type Journal Article Pages 1173-1179 DOI 10.1134/S1070428012090047 Authors V. A. Vasin, Ogarev Mordovian State University, ul. Bolshevistskaya 68, Saransk, 430005 Russia I. Yu. Bolusheva, Ogarev Mordovian State University, ul. Bolshevistskaya 68, Saransk, 430005 Russia V. V. Razin, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    The review considers transformations of ecdysteroids (mostly of 20-hydroxyecdysone and its derivatives) involving the A, B, C, and D rings of the steroid skeleton and the side chain, which are used in the synthesis of minor phyto- and zooecdysteroids and structural analogs of ecdysteroids. Content Type Journal Article Category Review Pages 1137-1161 DOI 10.1134/S1070428012090011 Authors N. A. Ves’kina, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia V. N. Odinokov, Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    ( R )- and ( S )-Ipsdienols, components of pheromones of bark beetles of the Ips family, were synthesized with high enantiomeric purity (〉98%) from 8-chloro-2-methyl-6-methylideneoct-2-en-4-ol prepared from ethyl 3-chloropropionate via cyclopropanation according to Kulinkovich. 8-Chloro-2-methyl-6-methylideneoct-2-en-4-ol was converted into the corresponding hydrogen phthalate whose stereoisomeric salts with ( R )- and ( S )-1-phenylethanamines were separated by crystallization, and subsequent hydrolysis of the latter and dehydrohalogenation with potassium tert -butoxide gave targeted ( R )- and ( S )-ipsdienols. Content Type Journal Article Pages 1168-1172 DOI 10.1134/S1070428012090035 Authors V. N. Kovalenko, Belarusian State University, pr. Nezavisimosti 4, Minsk, 220030 Belarus E. A. Matyushenkov, Belarusian State University, pr. Nezavisimosti 4, Minsk, 220030 Belarus Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    Quantum-chemical calculations at the RI-MP2/L1 level of theory showed that the most energetically favorable complexes of uracil and thymine with nitrosonium cation are those of n -type with NO + coordination at the nitrogen or oxygen atom. A correlation was found between the experimental and calculated affinities of the dioxo tautomer of thymine for nitrosonium ion ( A NO + ). A linear relation was revealed between A NO + values for structurally similar tautomers of uracil and thymine. Content Type Journal Article Pages 1216-1221 DOI 10.1134/S1070428012090114 Authors R. V. Andreev, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia G. I. Borodkin, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia V. G. Shubin, Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences, pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    The direction of ionic hydrogenation of estra-1,3,5(10),8,14-pentaenes with triethylsilane in the presence of trifluoroacetic acid is determined by the nature of substituents in the A and B rings. The hydrogenation of 7β-methyl-3-methoxy-D-homo-6-oxaestra-1,3,5(10),8,14-pentaen-17aβ-yl acetate gives mainly 9β-analog, which provides the possibility for synthesizing new inhibitors of enzymes responsible for metabolism of steroidal estrogens. Content Type Journal Article Pages 1245-1251 DOI 10.1134/S1070428012090175 Authors S. N. Morozkina, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia S. K. Nikol’skaya, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia A. S. Chentsova, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia A. S. Drozdov, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia G. L. Starova, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia S. I. Selivanov, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia A. G. Shavva, St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    Thermolysis of 3-aroylpyrrolo[1,2- d ][1,4]benzoxazine-1,2,4(4 H )-triones generates aroyl(2-oxo-1,4-benzoxazin-3-yl)ketenes which react as dienes at the aroylketene fragment in [4 + 2]-cycloaddition at the C=N bond of N,N ′-dicyclohexylcarbodiimide with formation of 3-[6-aryl-4-oxo-3-cyclohexyl-2-cyclohexylimino-3,4-dihydro-2 H -1,3-oxazin-5-yl]-2 H -1,4-benzoxazin-2-ones. Thermolysis of the latter is accompanied by elimination of N,N ′-dicyclohexylcarbodiimide, and aroyl(2-oxo-1,4-benzoxazin-3-yl)ketenes thus generated undergo cyclodimerization to produce 7-aroyl-6,10-dioxo-9-(2-oxo-2 H -1,4-benzoxazin-3-yl)-6,10-dihydrobenzo[ b ]pyrido[1,2- d ][1,4]oxazin-8-yl benzoates. Content Type Journal Article Pages 1233-1237 DOI 10.1134/S1070428012090151 Authors V. A. Maslivets, Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia A. N. Maslivets, Perm State National Research University, ul. Bukireva 15, Perm, 614990 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description: Synthesis of the first representative of 2-pyrazolyl-1,3-diselenanes, 3,5-dimethyl-1-(prop-2-en-1-yl)-4-(1,3-diselenan-2-yl)-1 H -pyrazole Content Type Journal Article Category Short Communications Pages 1259-1260 DOI 10.1134/S1070428012090217 Authors L. K. Papernaya, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia A. A. Shatrova, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia E. P. Levanova, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia A. I. Albanov, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia E. V. Rudyakova, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia G. G. Levkovskaya, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description: New synthesis of poly(phenothiazine-3,7-diyl) Content Type Journal Article Category Short Communications Pages 1263-1264 DOI 10.1134/S1070428012090230 Authors L. G. Shagun, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia I. A. Dorofeev, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia I. A. Tokareva, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia V. I. Smirnov, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia V. A. Shagun, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia M. G. Voronkov, Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, ul. Favorskogo 1, Irkutsk, 664033 Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description:    A new disaccharide block for OSW-1 natural steroidal antitumor agent was described. Regioisomeric 2- and 3- O - p -methoxybenzoyl derivatives of phenyl 1-thio-β- d -xylopyranoside and phenyl 2- O -acetyl-1-thio-β- l -arabinopyranoside derivatives blocked at positions 3 and 4 by R 3 Si groups were synthesized with a view to use them in the preparation of OSW-1 analogs modified at the disaccharide fragment. Content Type Journal Article Pages 1238-1244 DOI 10.1134/S1070428012090163 Authors L. S. Khasanova, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia F. A. Gimalova, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Z. R. Valiullina, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia N. K. Selezneva, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia R. M. Ganieva, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia L. V. Spirikhin, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia M. S. Miftakhov, Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences, pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia Journal Russian Journal of Organic Chemistry Online ISSN 1608-3393 Print ISSN 1070-4280 Journal Volume Volume 48 Journal Issue Volume 48, Number 9

Description: A number of mouse models for spinal muscular atrophy (SMA) have been genetically engineered to recapitulate the severity of human SMA by using a targeted null mutation at the mouse Smn1 locus coupled with the transgenic addition of varying copy numbers of human SMN2 genes. Although this approach has been useful in modeling severe SMA and very mild SMA, a mouse model of the intermediate form of the disease would provide an additional research tool amenable for drug discovery. In addition, many of the previously engineered SMA strains are multi-allelic by design, containing a combination of transgenes and targeted mutations in the homozygous state, making further genetic manipulation difficult. A new genetic engineering approach was developed whereby variable numbers of SMN2 sequences were incorporated directly into the murine Smn1 locus. Using combinations of these alleles, we generated an allelic series of SMA mouse strains harboring no, one, two, three, four, five, six or eight copies of SMN2. We report here the characterization of SMA mutants in this series that displayed a range in disease severity from embryonic lethal to viable with mild neuromuscular deficits.

Description: Insulin resistance (IR) is a key determinant of type 2 diabetes (T2D) and other metabolic disorders. This genome-wide association study (GWAS) was designed to shed light on the genetic basis of fasting insulin (FI) and IR in 927 non-diabetic African Americans. 5 396 838 single-nucleotide polymorphisms (SNPs) were tested for associations with FI or IR with adjustments for age, sex, body mass index, hypertension status and first two principal components. Genotyped SNPs ( n = 12) with P 〈 5 x 10 –6 in African Americans were carried forward for de novo genotyping in 570 non-diabetic West Africans. We replicated SNPs in or near SC4MOL and TCERG1L in West Africans. The meta-analysis of 1497 African Americans and West Africans yielded genome-wide significant associations for SNPs in the SC4MOL gene: rs17046216 ( P = 1.7 x 10 –8 and 2.9 x 10 –8 for FI and IR, respectively); and near the TCERG1L gene with rs7077836 as the top scoring ( P = 7.5 x 10 –9 and 4.9 x 10 –10 for FI and IR, respectively). In silico replication in the MAGIC study ( n = 37 037) showed weak but significant association (adjusted P -value of 0.0097) for rs34602777 in the MYO5A gene. In addition, we replicated previous GWAS findings for IR and FI in Europeans for GCKR , and for variants in four T2D loci ( FTO , IRS1 , KLF14 and PPARG ) which exert their action via IR. In summary, variants in/near SC4MOL , and TCERG1L were associated with FI and IR in this cohort of African Americans and were replicated in West Africans. SC4MOL is under-expressed in an animal model of T2D and plays a key role in lipid biosynthesis, with implications for the regulation of energy metabolism, obesity and dyslipidemia. TCERG1L is associated with plasma adiponectin, a key modulator of obesity, inflammation, IR and diabetes.

Description: Loss of dystrophin protein due to mutations in the DMD gene causes Duchenne muscular dystrophy. Dystrophin loss also leads to the loss of the dystrophin glycoprotein complex (DGC) from the sarcolemma which contributes to the dystrophic phenotype. Tyrosine phosphorylation of dystroglycan has been identified as a possible signal to promote the proteasomal degradation of the DGC. In order to test the role of tyrosine phosphorylation of dystroglycan in the aetiology of DMD, we generated a knock-in mouse with a phenylalanine substitution at a key tyrosine phosphorylation site in dystroglycan, Y890. Dystroglycan knock-in mice ( Dag1 Y890F/Y890F ) had no overt phenotype. In order to examine the consequence of blocking dystroglycan phosphorylation on the aetiology of dystrophin-deficient muscular dystrophy, the Y890F mice were crossed with mdx mice an established model of muscular dystrophy. Dag1 Y890F/Y890F / mdx mice showed a significant improvement in several parameters of muscle pathophysiology associated with muscular dystrophy, including a reduction in centrally nucleated fibres, less Evans blue dye infiltration and lower serum creatine kinase levels. With the exception of dystrophin, other DGC components were restored to the sarcolemma including α-sarcoglycan, α-/β-dystroglycan and sarcospan. Furthermore, Dag1 Y890F/Y890F / mdx showed a significant resistance to muscle damage and force loss following repeated eccentric contractions when compared with mdx mice. While the Y890F substitution may prevent dystroglycan from proteasomal degradation, an increase in sarcolemmal plectin appeared to confer protection on Dag1 Y890F/Y890F / mdx mouse muscle. This new model confirms dystroglycan phosphorylation as an important pathway in the aetiology of DMD and provides novel targets for therapeutic intervention.

Description: Facioscapulohumeral muscular dystrophy (FSHD), the most prevalent myopathy afflicting both children and adults, is predominantly associated with contractions in the 4q35-localized macrosatellite D4Z4 repeat array. Recent studies have proposed that FSHD pathology is caused by the misexpression of the DUX4 (double homeobox 4) gene resulting in production of a pathogenic protein, DUX4-FL, which has been detected in FSHD, but not in unaffected control myogenic cells and muscle tissue. Here, we report the analysis of DUX4 mRNA and protein expression in a much larger collection of myogenic cells and muscle biopsies derived from biceps and deltoid muscles of FSHD affected subjects and their unaffected first-degree relatives. We confirmed that stable DUX4-fl mRNA and protein were expressed in myogenic cells and muscle tissues derived from FSHD affected subjects, including several genetically diagnosed adult FSHD subjects yet to show clinical manifestations of the disease in the assayed muscles. In addition, we report DUX4-fl mRNA and protein expression in muscle biopsies and myogenic cells from genetically unaffected relatives of the FSHD subjects, although at a significantly lower frequency. These results establish that DUX4-fl expression per se is not sufficient for FSHD muscle pathology and indicate that quantitative modifiers of DUX4-fl expression and/or function and family genetic background are determinants of FSHD muscle disease progression.