ALBERT

Notes: 5,6-Dimethylidene-exo-2,3-epoxynorbornane (1) is reduced slowly by LiAlH4 in boiling tetrahydrofuran (THF) and furnishes a mixture of 5,6-dimethylidene-exo-2-norbornanol (2), 2,3-dimethylidene-anti-7-norbornanol (3) and principally 6-methyl-5-methylidene-anti-3-nortricyclanol (4). The yield of 4 is the highest for low initial concentrations of LiAlH4; it decreases in favour of alcohols 2 and 3 at high concentration of LiAlH4. The reduction of 1 with AlH3 in THF yields 3 as the major product, thus revealing an efficient synthesis of 7-substituted-2, 3-dimethyl-idenenorbornane derivatives. No alcohol 2could be isolated by LiEt3BH reduction of 1. LiAlD4 reduces 1 into the monodeuterated alcohols 2-d, 3-d and 4-d. The deuterium label is found in the endo-position at C (3) in 2-d, in the exo-position at C(5) in 3-d and in the methyl group of the tricyclic alcohol 4-d. Mechanistic limits for the formation of 2, 3 and 4 are discussed briefly.

Notes: The enthalpy of formation of tris(methylidene)-cyclopropane (“[3]radialene”, 1) has been determined as ΔHfO = 396 ± 12 kJ mol-1 from three fragmentation reactions of its molecular ion 1+ formed from 1 by photoionisation using synchrotron radiation. Comparative electron impact measurements using conventional mass spectrometry were also performed. A treatment of the latter data is described which leads to satisfactory agreement with the photoionization data. The experimental value of ΔHfO(1) is compared with various theoretical estimates. The strain energy of 1 is calculated to be 226.3 kJ mol-1. Linear extrapolation of this quantity from the increase of strain in passing from cyclopropane to methylidenecyclopropane yields 282.4 kJ mol-1. The discrepancy between these values, already predicted by Dewar and Baird ten years ago from theoretical calculations, is discussed on the basis of maximum overlap considerations. The enthalpy of formation of bis(methylidene)cyclopropane is predicted to be ΔHfO= 309 kJ mol-1.

Notes: Leaf-gland Pigments: 6-Novel p-Quinomethanes of the Abietane Series from Plectranthus parviflorus WILLDThe above mentioned plant accumulates in its red coloured leaf-glands a complex mixture of strongly dehydrogenated abietanols. They were separated (with difficulties) to yield 6 novel compounds. Spectroscopic and chiroptic data show them to be esters of either 11, 19-dihydroxy- or 2 α, 11-dihydroxy-abieta-5, 7, 9 (11), 13-tetraen-12-one 2a and 3a, respectively. Specifically, the 19-O-p-hydroxybenzoate (2d) parvifloron C, the 19-O-vanilloate (2c) parvifloron B, the 19-O-p-hydroxy-benzoate (2d) parvifloron C, the 19-O-3′,4′-dihydroxybenzoate (2e) parvifloron E, the 2 α-O-p-hydroxybenzoate (3b) parvifloron D, and the 2 α-O-3′,4′-dihydroxy-benzoate (3c) parvifloron F. Reduction by LiAlH4 splits the ester function and reduces the p-quinomethane to a colourless pyrocatechol derivative which, by air oxidation, regenerates the red p-quinomethane system of 2a and 3a.

Notes: A calculation of the modification of the optical absorptions of an isotropic sample by a uniform external electric field is presented. The induced orientational anisotropy, the Stark shift and the field. dependence of the transition moment are taken into account up to the second order in the field. The final expressions differ in the contributions from the transition polarizabilities from previous results.

Notes: The photoelectron spectrum of tris (methylidene)-cyclopropane 1 (“[3]radialene”) is reported and the electronic states of 1+ assigned. Jahn-teller activity in the degenerate states of 1+is discussed. Differences in the Franck-Condon profile of the first PE band and the Rydberg series in the Vacuum-UV./UV. absorption spectrum indicate for the Rydberg series (n=3) a 1A″2-species, which supports earlier tentative proposals. The high intensity absorption in the 5.5 eV-6 eV energy range of the latter spectrum recorded earlier are definitely due to impurities. The vibrational fine structure of a weak band system around 5.5 eV in our spectrum suggests for this transition S0→S2(1A′1), which is dipole forbidden but borrows intensity from S1(1E′) trough vibronic coupling via an e′-mode. From vapor pressure measurements ε(λmax=289 nm) = 9390± 1170 for gaseous 1 was found.

Notes: IR. and Raman spectra of LnONO3 (50-4,000 cm-1, Ln=La, Gd, Eu, and Dy) are reported and discussed. The low frequency region of the spectra reflects the cubic structure of these compounds. The dimensions of the cubic unit cells determined by X-Ray powder diagrams are: 12.81 ± 0.05 Å for EuONO3, 12.69 ± 0.05 Å for GdONO3, and 12.67 ± 0.05 Å for DyONO3. The vibrational frequencies of the nitrato group are consistent with a bidentate nitrate of C2v symmetry. The synthesis of anhydrous Ln (NO3)3 (Ln=La, Gd, Eu, and Dy) by dehydration of the corresponding penta- or hexahydrates is described. The IR. and Raman spectra (50-4,000 cm-1) are analysed. Splitting of the bands point to a complex structure of these compounds. All six vibrational modes of the nitrato group are observed and the data are again consistent with bidentate NO-3 moieties. Finally, an analytical control of the purity of Ln (NO3)3 is suggested.

Notes: Synthesis of 3-Dimethylamino-3a,4,5, 7a-tetrahydro-1H-isoindol-1-ones by Intramolecular Diels-Alder ReactionThermolysis of N2-acylamidines, the acyl group of which derives from an α,β,γ,δ-unsaturated carboxylic acid (2, 5-7), yields 3-dimethylamino-3a,4,5,7a-tetrahydro-1H-isoindol-1-ones (3,8-10, Schemes 1 and 3) in 63-78%. Only the thermodynamically controlled cis-fused ring system is formed. The starting materials are readily available by the reaction of 3-dimethylamino2H-azirines (1 and 4) and carboxylic acid chlorides.

Notes: Reactions of Aziridino-nitrenes: Synthesis of Polycyclic Bisaziridines and 1,2-Bisaziridino-diazenesVorgetragen in der Versammlung der Schweizerischen Chemischen Gesellschaft in Bern am 7.Oktober 1977.7-Amino-7-azabicyclo[4.1.0]-3-heptene (11b), cis-9-amino-9-azabicyclo[6.1.0]-nonane (12b), cis-9-amino-9-azabicyclo[6.1.0]-(4Z)-nonene (13b), as well as exo- and endo-3-amino-3-azatricyclo[3.2.1.02,4]-6-octene (14b and 15b) were synthesized by addition of oxidatively generated phthalimido-nitrene (6) to 1,4-hexadiene, (Z)-cyclooctene, (1Z,5Z)-cyclooctadiene, and bicyclo[2.2.1]heptadiene, respectively, followed by hydrazinolysis of the corresponding N-phthalimido-aziridines 11a-15a.Lead tetraacetate oxidation of the two unsaturated N-amino-aziridines 11b and 15b at -70° yielded diazapolycyclic structures by intramolecular addition of the intermediate aziridino-nitrenes 11c and 15c to the δ, ε-situated C, C-double bond; the products obtained in good yields were 1,5-diazatetracyclo [3.3.0.02,8. O4,6]-octane (16) and 3,7-diazapentacyclo [3.3.1.02,4.03,7.06.8] nonane (17), respectively Oxydation of the unsaturated N-amino-aziridine 13b under the same conditions did not cause intramolecular addition of the nitrene 13c to the ε, ζ-situated C, C-double bond; instead 1,2-bis (cis-9-azabicyclo [6.1.0]-(4Z)-nonen-9-yl)-diazene (20) was obtained in low yield and (1Z, 5Z)-cyclooctadiene as the main product. Both products can be rationalized as derived from the intermediate nitrene 13c with 13b and the olefine as the result of a fragmentation of 13c under extrusion of N2. As. expected, oxidation of the saturated N-amino-aziridine 12b led to the 1,2-bisaziridino-diazene 21 and (Z)-cyclooctene in a ratio of 4:6. Surprisingly, oxidation of 7-amino-7-azabicyclo [4.1.0]-heptane (10b) produced only fragmentation of the corresponding nitrene 10c to cyclohexene. Finally, oxidation of the exo-N-amino-aziridine 14b yielded a complex not yet resolved product mixture in low overall yield. Attempts to add the oxidatively generated aziridino-nitrene 12c to cyclohexene, methyl acrylate, and dimethylsulfoxide were without success.Heating the 1,2-bisaziridino-diazenes 20 and 21 at their respective m.p. temperatures caused thermal fragmentation to occur with evolution of nitrogen. The bisaziridines 26 and 28 as well as the aziridines 27 and 29, respectively, were isolated. These products could be the result of a radical pathway, whereas a small amount of (Z)-cyclooctene, also generated in the thermolysis of 21, might be formed by a competing cheletropic pathway.The 1H-NMR-spectra of the derivatives of cis-9-azabicyclo[6.1.0]nonane, namely of 12a, 12b, 21, 28 and 29, showed signals for some of the aliphatic protons which were separated from the others at relatively low field (around 2.5-1.8 ppm). These signals accounted for 4 (with 12b for 2) protons in each of the cis-9-azabicyclo[6.1.0]nonane subunits, i.e. more than the 2 expected for the aziridine methine protons. The additional signals must be assigned to methylene protons (2 or even 4 of them) probably situated on the other side of the eight membered ring and deshielded by the motion-average proximity to the aziridine nitrogen atom.

Notes: On the Carotenoids Flavoxanthin and Chrysanthemaxanthin: 1H-NMR., 13C-NMR. and Mass Spectra, Absolute Configuration, Survey of Published DataVery pure flavoxanthin (1) and chrysanthemaxanthin (2) have been reisolated from flower heads of Taraxacum officinale. Both compounds were characterized by chromatographic, chemical and chiroptical data and extensive NMR. measurements. Examination of many published data on 1 and 2 led to the conclusion that flavoxanthin has often been mistaken for chrysanthemaxanthin and vice versa.Chemical degradation of 1 and 2 to (-)-loliolide (5) coupled with NMR. evidence (ASIS, spin-decoupling, NOE) allowed the assignment of the absolute configurations of 1 and 2. Thus (+)-flavoxanthin is (3S,5R,8R, 3′R,6′R)-5, 8-epoxy-5, 8-dihydro-β, ε-carotene-3, 3′-diol and (+)-chrysanthemaxanthin its C(8)-epimer.

Notes: Synthesis and Chirality of (5S,6R)-5,6-Epoxy-5,6-dihydro-β,β-carotene and (5R,6R)-5,6-Dihydro-β,β-carotene-5,6-diol, a Compound with Unexpected Solubility CharacteristicsWittig-condensation of azafrinal (1e) with the phosphorane derived from 7 leads to a (1:3)-mixture of (E)-9′- and (Z)-9′-β,β-carotene-diol 3, from which pure and optically active 3 ((5R,6R)-5,6-dihydro-β,β-carotene-5,6-diol) has been isolated as bright violet leaflets, m.p. 168°. Due to the trans-configuration of the diol moiety and to severe steric hindrance, hydrogen bonding is reduced to such an extent, that 3 behaves much more as a hydrocarbon than as a diol. There is good evidence that the so-called ‘β-oxycarotin’ obtained by Kuhn & Brockmann [15] by chromic acid oxidation of β, β-carotene is the corresponding racemic cis-diol. 3 has been converted into (5S, 6R)-5,6-epoxy-5.6-dihydro-β,β-carotene (4), m.p. 156°. This transformation establishes for the first time the chirality of a caroteneepoxide (without other O-functions).Full spectral and chiroptical data including a complete assignement of 13C-chemical shifts for azafrin methyl ester and 3 are presented.

Notes: As an extension of previous studies on the total synthesis of (2R,4′R,8′R)-α-tocopherol (1) [1] [2], (S)-(-)-2-(6-benzyloxy-2,5,7,8-tetramethylchroman)acetic acid (6), a pivotal intermediate, possessing the absolute configuration required for construction of 1 was prepared by optical resolution of the racemic modification 11. the latter substance was obtained by two routes, one emanating from the hydroxy acetal 7 [1] and the other based upon the Lewis acid mediated cycloaddition of trimethylhydroquinone to rac.-3-hydroxy-3-methylpent-4-en-l-yl acetate (16) giving rac. ethyl 2-(6-hydroxy-2,5,7,8-tetramethyl-chroman)acetate (12).

Notes: Thermodynamic study of charge transfert complexes (n-σ*) in solutionCharge transfer complexes of quinoline and substituted quinolines (donors) with iodine, iodine chloride, and iodine bromide (acceptors) have been studied spectrophotometrically in CCl4. The 1:1 stoechiometry of these complexes was verified by means of the continous variations method and the appearance of isosbestic points. Simultaneous determination of the equilibrium constant and enthalpy of adduct formation was carried out by calorimetry.It was observed for every donor that the equilibrium constants of the complexes studied increase with the strength of the acceptors. A linear correlation between enthalpy of adduct formation and donor strength was obtained only for the complexes Donor ICI.

Notes: Syntheses of jasmone (1), methyl jasmonate (3) and γ-jasmolactone (2) are reported, (Z)-nona-1, 6-dien-3-one (4) serving as common intermediate.

Notes: The Conversion of Eperuic Acid into Ethers of the enantio-14, 15-Dinorlabdane Series5 and 6 are strongly odiferous substances of the ambra-type. Their enantiomers 7 and 8, hitherto unknown, have been synthesized from eperuic acid (4) and their olfactory properties compared with those of 5 and 6. 4 was esterified by CH2N2 and dehydrogenated with (C6H5Se)2/H2O2 to the α,β-unsaturated ester 9 (61%). Oxidation by KMnO4 in acetone yielded the ketone 3 (60%). Epoxidation followed by treatment with acid converted 3 into the acetals 7 (61%) and 8 (14%). 7 and 8 differ from 5 and 6 in odor intensity, and 6 and 8 show slightly different odor quality.

Notes: The natural products methyl dehydrojasmonate (1) and tuberolactone (2) have been synthesized from methyl jasmonate (3) and jasmolactone (4) resp., via sulfenylation-sulfoxide pyrolysis.

Notes: Comparative investigation of reactivities and ion structures upon electron impact induced degradations of the isomeric hydroxy cinnamic acid methyl estersBy analysis of energy release data in metastable peaks it is shown that m- and p-hydroxy cinnamic acid methylesters retain specific structural features upon degradation under electron impact, although their spectra are very similar and the shapes of the metastable peaks due to the initial methoxy cleavage are identical. A pronounced charge radical localization in the molecular ion is indicated. The o-isomer is found to yield a coumarin type structure by elimination of methanol, whose further degradation by decarbonylation involves at least three different mechanisms. The resulting ion structures are different from benzofuran.

Notes: 2-Thiopyridone (2-mercaptopyridine, 1) was found to be a very suitable reagent for removing the Nα-o-nitrophenylsulfenyl (NPS-) group in both conventional and solid-support peptide synthesis. A 3- to 5-molar excess of the reagent together with an equivalent amount of glacial acetic acid in methanol, dimethylformamide, or methylene chloride produces the soluble, stable mixed disulfide, 2-nitrophenyl 2-pyridyl disulfide (2), and the Nα-deprotected amino-acid or peptide. The yields are quantitative in less than 5 min if all educts are dissolved, in about 20 to 30 min in solid-support synthesis. No modifications of either the indole side-chain of tryptophan or of a series of side-chain protecting groups, in particular of the t-butyl type, are produced. No adverse side-reactions (insoluble disulfides) were observed. The procedure is illustrated with a series of amino-acid derivatives and with the solid-support synthesis of [5-leucine]-enkephalin.

Notes: The two novel tricyclic C10H16 compounds anti- and syn-tricyclo [4.2.1.12,5]- decane (16 and 17, respectively) were synthesized starting either from the photodimer 2 (anti) or the two cycloaddition products 8 (anti) and 9 (syn).

Notes: The title condensations gave respectively: gem-bisarylated cyclic amines 3a-k or monoarylated unsaturated cyclic amines 4a-g, 1,3-bisarylated cyclohexadienes 6a, 6b, the condensed bicyclo [2,2,2]-octane 8. In addition the aromatic ketone 9 gave the fluorenone 10 on treatment with polyphosphoric acid (PPA).

Notes: Nickel-catalysed Synthesis of α-NornicotinesSchiff's bases 1 and butadiene generally co-oligomerize on nickel catalysts to yield octatrienyl-substituted amines 2 and octadienyl-substituted imines 3.Schiff's bases 4 and 5, on the other hand, react with 1, 3-dienes to give new [3+2]-cycloadducts 6. In addition to the appropriately functionalized α-nornicotine derivatives some higher oligomers are formed.

Notes: The ligands (L) bis (2-pyridyl) methane (BPM) and 6-methyl-bis (2-pyridyl)methane (MBPM) form the three complexes CuL2+, CuL22+, and Cu2L2H-22+ with Cu2+. Stability constants are log K1 = 6.23 ± 0.06, log K2 = 4.83 ± 0.01, and log K (Cu2L2H-22+ + 2H2+ ⇌ 2 CuL2+) = -10.99 ± 0.03 for BPM and 4.56 ± 0.02, 2.64 ± 0.02, and -11.17 ± 0.03 for MBPM, respectively. In the presence of catalytic amounts of Cu2+, the ligands are oxygenated to the corresponding ketones at room temperature and neutral pH.With BPM and 2,4,6-trimethylpyridine (TMP) as the substrate and the buffer base, respectively, the kinetics of the oxygenation can be described by the rate law \documentclass{article}\pagestyle{empty}\begin{document}$${{ - {\rm d}\left[{{\rm O}_2 } \right]} \mathord{\left/ {\vphantom {{ - {\rm d}\left[{{\rm O}_2 } \right]} {{\rm dt}}}} \right. \kern-\nulldelimiterspace} {{\rm dt}}} = {{k_1 \left[{{\rm CuL}_2^{2 + } } \right]} \mathord{\left/ {\vphantom {{k_1 \left[{{\rm CuL}_2^{2 + } } \right]} {\left[{{\rm H}^ + } \right]}}} \right. \kern-\nulldelimiterspace} {\left[{{\rm H}^ + } \right]}} + k_2 \left[{{\rm CuL}_2^{2 + } } \right]\left[{{\rm TMP}} \right] + {{k_3 \left[{{\rm CuL}^{2 + } } \right]} \mathord{\left/ {\vphantom {{k_3 \left[{{\rm CuL}^{2 + } } \right]} {\left[{{\rm H}^ + } \right]}}} \right. \kern-\nulldelimiterspace} {\left[{{\rm H}^ + } \right]}} + {{k_4 \left[{{\rm Cu}_2 {\rm L}_2 {\rm H}_{ - 2}^{2 + } } \right]} \mathord{\left/ {\vphantom {{k_4 \left[{{\rm Cu}_2 {\rm L}_2 {\rm H}_{ - 2}^{2 + } } \right]} {\left[{{\rm H}^ + } \right]}}} \right. \kern-\nulldelimiterspace} {\left[{{\rm H}^ + } \right]}}$$\end{document} with k1 = (5.9 ± 0.2) · 10-13 mol l-1 s-1, k2 = (4.0 ± 0.6) · 10-4 mol-1 ls-1, k3 = (1.1 ± 0.1) · 10-12 mol l-1 s-1, and k4 = (9 ± 2) · 10-14 mol l-1 s-1.

Notes: Nickel-catalysed Isomerization of Unsaturated AzocompoundsUnsaturated azocompounds, produced by the nickel-catalysed reaction of butadiene with hydrazones, can be isomerized in presence of the same nickel catalyst. The influence of nickel concentration, temperature and structure of the azocompound on this rearrangement is described.

Notes: Nickel-catalysed Reaction of 2-Aza-1, 3-butadienes with 1, 3-ButadieneThe nickel-catalysed reaction of butadiene with 2-azabutadienes yields a mixture of 1 aza-1,5,9-cyclododecatrienes, N-alkylidene-divinylcyclohexylamines and open chained 2:1 adducts.

Notes: The preparation of the vitispiranes 9 and 10, identified among the volatiles of vanilla, from the theaspiranes 1 and 2 via the intermediates 4 and 5 and the allyl alcohols 7 and 8, respectively, is described. The theaspiranes 1 and 2 can be obtained from the compounds 11-15 or 24-26.

Notes: The binding of various flavins by apoflavodoxins from P. elsdenii and A. vinelandii has been studied by the temperature-jump technique using fluorescence detection. P. elsdenii apoflavodoxin interacts only with flavins possessing 5 carbon atoms in the N(10) side chain and a terminal phosphate group. Employing a wide range of concentrations of deoxy-FMNFlavin = 3,4-dimethyl-lO-substituted isoalloxazine = 3,4-dimethyl- lO-substituted-2,3,4,10-tetrahydro-benzo[g]-pteridine-2,4-dione; FMN = riboflavin-5′-monophosphate. and apoflavodoxin only one relaxation process was observed, indicating a one-step binding mechanism. With native flavodoxin no relaxation could be observed.The kinetic parameters of the interaction of A. vinelandii apoflavodoxin with various flavin analogs (Structure I) have also been investigated. The interaction between apoflavodoxin and flavin derivatives carrying an ionizable, terminal functional group on the side chain becomes very weak when the number of the side chain carbon atoms is decreased below 4. This observation is interpreted in terms of repulsive forces due to negatively charged amino acid residues located in the flavin side chain binding region of the apoflavodoxin. All complexes studied revealed only one relaxation process. This observation is in contradiction with published results [10]. The published traces are instrumental artifacts.

Notes: A short synthesis of 3,5-dimethyl-1,2,4-trithiolane (1), a well-known constituent of processed meat, is described.

Notes: In the presence of Ni2+ the template reaction between 2,6-diacetylpyridine and 4-(2-dimethylaminoethyl)- or 4-(2-hydroxyethyl)-1, 7-diamino-4-azaheptane yields the complexes of either the open-chain ligand (3 and 11) or of the macrocycle (4 and 12). Reduction of the imino group in 4 and 12 with PtO2/H2 gives 5 and 13, respectively. In the case of the dimethylamino derivative 5 a mixture of at least four isomers was obtained. These were partially separated by chromatography on Sephadex SP-25 cation exchanger. Through demetalation of the Ni2+ complexes by cyanide the new macrocycles 7 and 14 were isolated, from which the corresponding Zn2+ and Cu2+ complexes were prepared.The macrocyclic Ni2+-complexes 4, 12, 5 and 13 can exist in two forms depending on the pH of the solution. At low pH protonation of the dimethylamino or hydroxy group in the side chain occurs. The metal ion is then bound to the four nitrogen atoms of the macrocycle in a square planar ligand field. At higher pH, however, the dimethylamino or hydroxy group (the last one also in its deprotonated form) can coordinate to one of the axial positions, whereby pseudooctahedral coordination geometry is induced. This reaction can be quantitatively described by a reversible acid-base equilibrium, the pKH of which greatly depends on the nature of the functional group, the degree of unsaturation of the macrocycle and the metal ion.The acid-base reaction and the concomitant structural change are a direct consequence of the unique combination of the rigid and kinetically stable structure of the macrocycle and of the flexible and kinetically labile functional group of the side chain.

Notes: The He (Iα) photoelectron spectra of the four unsaturated oxides 3,4-dihydropyran (6), γ-pyran (7), 2, 3-dihydro-1, 4-dioxin (9) and 1, 4-dioxin (10) are reported and analysed. Band assignments are based on ab-initio calculations, using the STO-3G basis set. The proposed orbital sequences (with reference to the coordinate systems given in Table 1) are, for the top three orbitals: 6, π, nσ, nπ; 7, 3b1(π), 1a2(π), 11a1(σ); 9, 11b(π), 12a(σ), 11a(π); 10, 2b3u(π), 1b1g(π), 6ag(σ). Finally the (almost) localized π-orbitals have been computed by the Foster-Boys localization procedure.

Notes: The spiro-lactone 3 was obtained by N-bromosuccinimide (NBS) oxidation of the carboxylate 2 at - 20°. When 2 was oxidized at 10° the spiro-lactone 4 was the main product. Compound 4 was rearranged with triethylamine to the spiro-lactone 9 whereas the stereoisomeric spiro-lactones 14 and 15 were obtained by NBS oxidation of the carboxylate 13. The ketones 3, 4, 9, 14 and 15 were reduced with NaBH4 to the corresponding alcohols 5, 6, 10, 16 and 18 respectively; these were hydrogenated to the alcohols 7, 8, 11 and 20. The allylic alcohols 5 and 6 gave the benzochromanone 1 when heated in polyphosphoric acid whereas the benzochromanones 12 and 21 were obtained from the alcohols 10 and 16 respectively.

Notes: The Reaction of Phenols with N-substituted MaleinimidesPhenoxysuccinimides are formed by the base catalysed addition of phenols to N-substituted maleinimides. In the presence of catalytic amounts of tertiary aliphatic amines yields as high as 90% are obtained. A series of adducts of mono-and di-phenols to mono- and bismaleinimides is described. Pure phenoxysuccinimides are stable compounds but the basic catalysts of their formation give rise to their decomposition into the phenolic component and oligomeric maleinimide. A nucleophilic reaction mechanism both for the formation and the decomposition is discussed. A new crosslinked addition polymer from a diphenol and a bismaleinimide with a surprisingly high heat stability is described.

Notes: Macrocyclic and noncyclic neutral ionophores. Effect of the macrocyclic ring on the ion selectivityA series of macrocyclic 3, 6-dioxaoctanedioic diamides was prepared. Their ion selectivity in membranes was compared with nonmacrocyclic analogues. The ion selectivity as well as the capability to extract ions from aqueous solutions to an organic phase decreases with decreasing ring size.

Notes: Structure and properties of 5-epi-flavoxanthin and 5-epi-chrysanthemaxanthinThe absolute configurations of 5-epi-flavoxanthin (6) and 5-epi-chrysanthemaxanthin (7) prepared by acid catalysed rearrangement of semi-synthetic lutein epoxide 5 are shown to be (3S, 5S, 8R, 3′R, 6′R) and (3S, 5S, 8S, 3′R, 6′R), respectively. Contrary to published data [5] the relationship of the polyene chain and H3(18) on the dihydrofurane ring is cis for the pair of stereoisomers having a Δδ = δ (H—C(7)) - δ (H—C(8)) = 0,22 ppm and 3J ≡ 0. These conclusions are in full accord with the chiroptical data.

Notes: Influence of the lipophilicity of 3,6-dioxaoctanedioic diamides on their ion carrier propertiesA series of lipophilic 3,6-dioxaoctanedioic diamides (potential ionophores for Ca2+) have been prepared. With increasing lipophilicity the ionophoric behavior of these ligands vanishes. This loss is shown to be due to kinetic limitations in the exchange reactions between aqueous phase and membrane phase.

Notes: Oscillating Chemical Reactions. 11. Behaviour of the “induction period” in the BrO3-/Ce4+/Cyclohexanon and BrO3-/Ce4+/Cyclopentanon systems(1)The addition of α-monobromoketone, one of the products of reaction of the BrO3-/Ce4+/Cyclohexanon (S1) and BrO3-/Ce4+/Cyclopentanon (S2) oscillating systems, decreases and even suppresses the induction period (τind.) in the case of S2.Such is not the case with S1: τind. increases and the oscillations can even be completely inhibited.(2)The order of addition of the reagents and the time lapse (tadj.) preceding the addition of the last of them influences τind., particularly when the last reagent added is Ce4+.(3)In our experimental conditions, the inhibition of the oscillatory phenomenon by Cl- ions is definite only for | Cl- | ≥ 5,0 · 10-2M (S1) and |Cl-| 〉 2,5 · 10-3M (S2); for lower concentrations τind. increases with | Cl-|.

Notes: Preparation of Cortexon-Analogs with Conformatively Fixed Side ChainThe synthesis of cortexon-analogs with a conformatively fixed side chain is described. The key step in the synthesis consists of an intramolecular displacement of bromine in position 21 by the oxygen of a 17α-hydroxymethyl group.

Notes: Allyl sulfides and a selenide are metallated and silylated with chloro (penta-methyl)disilane. Treatment of the resulting disilanylmethyl sulfides 4 with trimethyloxonium tetrafluoroborate furnishes 1,1-disilyl-2-alkenes 5 in good yields. Some synthetic possibilities of 5 are outlined.

Notes: Starting from 5-chloro-2-pentanone (1) the naturally occurring 10-membered lactone phoracantholide J (8a) has been synthesized as its racemate in a sequence of six steps (Scheme 2). Salient features of the syntheis include an internal selenium assisted acetal formation (4→5) and a stereoselective Claisen rearrangement (6→7→8). This general synthetic strategy offers an alternative approach towards the construction of macrocyclic lactones.

Notes: The conversion of α-hydroxythioacetals to ketene thioacetals possessing an unprotected carbonyl function is described. Besides the intrinsic utility of this transformation it is of interest to recognize that ketene thioacetals are protected carboxyl groups.

Notes: During the reaction of allyl ethers, allyl sulfides and allyl selenides with in situ prepared dichloroketene (1), 2 competing pathways are observed. Besides [2+2]-cycloaddition, an unprecedented [3,3]-sigmatropic (Claisen) rearrangement via a 1,3-dipolar intermediate takes place. It leads to O-, S- or Se-esters of α,α-dichloro-γ, δ-unsaturated acids containing an inverted allylic group. Starting from cyclic n-membered α-vinyl-substituted ethers, lactones with n+4-membered rings are formed. A very facile synthesis of the naturally occurring macrolides (±)-phoracantholide I (10) and (±)-phoracantholide J (11) illustrates the synthetic utility of this new ‘ketene’ Claisen rearrangement.

Notes: Syntheses of Sulfonated Derivatives of 4-Amino-1, 3-dimethylbenzene and 2-Amino-1, 3-dimethylbenzeneDirect sulfonation of 4-amino-1, 3-dimethylbenzene (1) and sulfonation of 4-nitro-1,3-dimethylbenzene (4) to 4-nitro-1,3-dimethylbenzene-6-sulfonic acid (3) followed by reduction yield 4-amino-1,3-dimethylbenzene-6-sulfonic acid (2). The isomeric 5-sulfonic acid (5) however is prepared solely by baking the acid sulfate salt of 1. Reaction of sulfur dioxide with the diazonium chloride derived from 2-amino-4-nitro-1,3-dimethylbenzene (7) leads to 4-nitro-1,3-dimethylbenzene-2-sulfonyl chloride (8), which is successively hydrolyzed to 4-nitro-1,3-dimethylbenzene-2-sulfonic acid (9) and reduced to 4-amino-1, 3-dimethylbenzene-2-sulfonic acid (6). Treatment of 4-amino-6-bromo-1,3-dimethylbenzene (12) and 4-amino-6-chloro-1, 3-dimethylbenzene (13), the former obtained by reduction of 4-chloro-6-nitro-1,3-dimethyl-benzene (10) and the latter from 4-chloro-6-nitro-1, 3-dimethylbenzene (11), with oleum yield 4-amino-6-bromo-1,3-dimethylbenzene-2-sulfonic acid (14) and 4-amino-6-chloro-1,3-dimethylbenzene-2-sulfonic acid (15) respectively; subsequent carbon-halogen hydrogenolyses of 14 and 15 lead also to 6 (Scheme 1).Baking the acid sulfate salt of 2-amino-1, 3-dimethylbenzene (17) gives 2-amino-1, 3-dimethylbenzene-5-sulfonic acid (16), whereas the isomeric 4-sulfonic acid (18) can be prepared by either of the following three possible pathways: Sulfonation of 2-nitro-1,3-dimethylbenzene (20) to 2-nitro-1,3-dimethylbenzene-4-sulfonic acid (21) followed by reduction or sulfonation of 2-acetylamino-1,3-dimethylbenzene (19) to 2-acetylamino-1,3-dimethylbenzene-4-sulfonic acid (22) with subsequent hydrolysis or direct sulfonation of 17. Further sulfonation of 18 yields 2-amino 1,3-dimethylbenzene-4,6-disulfonic acid (23), the structure of which is independently confirmed by reduction of unequivocally prepared 2-nitro- 1,:3-dimethylbenzene-4,6-disulfonic acid (24)(Scheme 2).

Notes: On the way to the fullerene-acetylene hybrid carbon allotropes 2 and 6, the oxidative homocoupling of the 2-functionalized 1-ethynylated C60 derivatives 11, 12, 14, and 15 was investigated. Under Glaser-Hay conditions, the two soluble dumbbell-shaped bisfullerenes 17 and 18, with two C60 moieties linked by a buta-1,3-diynediyl bridge, were formed in 52 and 82% yield, respectively (Scheme 2). Cyclic-voltammetric measurements revealed that there is no significant electronic communication between the two fullerene spheres via the buta-1,3-diynediyl linker. Removal of the 3,4,5,6-tetrahydro-2H-pyran-2-yl (Thp) protecting groups in 18 gave in 80% yield the highly insoluble dumbbell 19 with methanol groups in the 2,2′-positions of the buta-1,3-diynediyl-bridged carbon spheres. Attempted conversion of 19 to the all-carbon dianion 6 (C1242-) via base-induced elimination of formaldehyde was not successful presumably due to exo-dig cyclization of the formed alkoxides. The occurrence of this cyclization under furan formation was proven for 2-[4-(trimethylsilyl)buta-1,3-diyn-1-yl][60]fullerene-1-methanol (21), a soluble model compound for 19 (Scheme 3). To compare the properties of ethynylated fullerene mono-adducts to those of corresponding higher adducts, hexakis-adducts 26 and 28 with an octahedral functionalization pattern resulting from all-e (equatorial) additions were prepared by the reversible-template method of Hirsch (Scheme 4). Reaction of the ethynylated mono-adducts 25 or 13 with diethyl 2-bromomalonate/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the presence of 1,9-dimethylanthracene (DMA) as reversible template led to 26 and 28 in 28 and 22% yield, respectively. Preliminary experiments indicated a significant change in reactivity and NMR spectral properties of the fullerene addends with increasing degree of functionalization.

Notes: Supports consisting of a thin layer (2-10%) of polystyrene (PS) grafted onto a poly(tetrafluoroethylene) (PTFE) core are an interesting alternative to controlled pore glass (CPG) carriers in oligonucleotide synthesis. The beads are mechanically stable, do not show significant swelling, and allow effective removal of substrates by short washing steps with organic solvents. PTFE-PS as an organic polymer has generally more hydrophobic properties than inorganic polymer supports and, therefore, is well compatible with organic solvents such as anhydrous MeCN. We found PTFE with a content of 2-3% PS graft to be a very good support for the synthesis of oligonucleotides of extended length. In comparison, PTFE with 5-10% grafted PS is especially useful for large-scale syntheses. Functionalization procedures minimized in the extent of side reactions are described as well as examples for the use of the supports in syntheses of oligonucleotides both on large scale and of extended chain length.

Notes: Reaction of ‘Push-Pull’ Enynes with Acids. First Observation of a Rearrangement of 5-Chloro-5-(dialkylamino)pentadienals‘Push-pull’-enynes 7 react easily with HCl as well as with AcOH to give 5-amino-5-chloropentadienals 8 and 5-(acetoxy)-5-aminopentadienals 13 as well as the corresponding ketones. In view of a postulated rearrangement of compounds 8 and 13 (Scheme 2), both types of compounds have been treated with traces of acid. While no definite reaction is observed in case of 13, HCl-addition products 8 easily and quantitatively rearrange to give 2H-pyran-2-iminium chlorides 10 which are the postulated intermediates of the rearrangement 8→12 (Scheme 2).

Notes: The self-assembly of alkaline folates in isotropic water solutions, with or without added salts, has been investigated by small-angle neutron-scattering, circular-dichroism, and NMR techniques. The assembled species are chiral, cylindrical aggregates of finite length, composed of stacked tetramers; each tetramer is formed by Hoogsteen-bonded folate residues. The assembly process is more efficient in the presence of an excess of NaI ions, leading to longer aggregates with stronger tetramer-tetramer-tetramer interaction. In pure water, the rods are shorter and the tetramer-tetramer interaction weaker. Association between folates can be detected by circular-dichroism spectroscopy starting from a concentration of 6· 10-4 mol l-1, well below the critical concentration for the formation of the cholesteric mesophase (ca. 0.5 mol l-1).

Notes: Bromination of the monosilylated dialkynylated monomer 1a (Scheme 1), dimer 3 and tetramer 5 by N-bromosuccinimide (NBS) in the presence of CF3COOAg gave 2, 4, and 6, respectively, in over 93%. Similar conditions led to bromodesilylation. Either silyl group of the diprotected monomer 1c was selectively removed by bromolysis. On the one hand, bromodesilylation of 1c gave 2 in yields varying between 80 and 99%. On the other hand, bromodesilylation of 7, obtained from 1c by hydrolytic removal of the tetrahydro-2H-pyran-2-yl (Thp) group, yielded 91% of 8. Mechanistic considerations suggested that the deprotective bromination should be improved by replacing the Me3Si by a Me3Ge group. Indeed, bromodegermylation of 1b was quantitative and ca. 60 times faster than bromodesilylation of 1c. The Me3Si and Me3Ge groups can be used for an orthogonal protection/activation of dialkynes. This was shown by desilylating 12 to 11 (Scheme 2), while bromination yielded 13. Both reactions proceeded in high yields; 9 was isolated as a minor by-product of 13. The reactivity towards bromolysis decreases in the series H-DOPS 〉 Me3Ge ≈ H 〉 Me3Si 〉 Thp-DOPS (DOPS = [dimethyl(oxy)-p ropyl]dimethylsilyl). Orthogonal bromolysis of DOPS- and Me3Ge-substituted dialkynes is slightly more selective than the one of Me3Si- and Me3Ge-substituted analogues. Coupling of 7 with the bromoalkyne 2 gave the dimer 15 (76%), 14 (2%), and 16 (4%) (Scheme 3). The binomial synthesis was optimized so that each cycle, doubling the size of the precursor, requires the minimal number of transformations (Scheme 4). The orthogonally protected monomer 1b, dimer 19, and tetramer 22 were, on the one hand, hydrolyzed to the alcohols 18 (95%), 21 (91%), and 24(91%), respectively, and, on the other hand, bromodegermylated to 2 (99%), 4 (97%), and 6(93%). Cross-coupling of 18 with 2, 21 with 4, and 24 with 6 gave the orthogonally protected dimer 19 (73%), tetramer 22 (87%), and octamer 25 (83%), respectively.

Notes: The synthesis of novel thiazole-containing complexing agents and their luminescence properties with EuIII and TbIII ions are reported. One of these terpyridine analogues was also tested as an EuIII labelling reagent, and its luminescence properties as an antibody conjugate were studied.

Notes: Chemical screening of the secondary metabolites from Halenia corniculata L. (CORNAZ), by LC/UV,LC/TSP-MS (thermospray), and LC/ES-MS (electrospray) was used for the targeted isolation of corniculoside (1), a new biosidic ester secoiridoid. The structure was established as 7-β-[(E)-4′-O-(β-D-glucopyranosyl)caffeoyloxy]-sweroside by 1D- and 2D-NMR, LC/UV, LC/MS, and FAB-MS data, in combination with chemical reactions.

Notes: Addition reactions of organometallic reagents with 4,4-disubstituted 1,3-thiazole-5(4H)-thiones were studied. Whereas the reactions with alkyllithium and alkyl Grignard reagents occurred in the thiophilic manner, the carbophilic addition was observed with allyllithium and allyl Grignard reagents. A radical reaction mechanism is proposed for rationalizing these observations (Scheme 5). A radical cyclization of the prepared 5-allyl-4,5-dihydro-1,3-thiazole-5-thiol derivatives yielded 1,6-dithia-3-azaspiro[4.4]non-2-enes (Table 4).

Notes: The syntheses of various fluorocarbon/fluorocarbon and fluorocarbon/hydrocarbon rac-1,2- and 1,3-di-O-alk(en)ylglycerophosphocholines and rac-1,2-di-O-alkylglycerophosphoethanolamines (see Fig.2), which may be used as components for drug-carrier and delivery systems, are described together with some results concerning their biological tolerance. They were obtained by phosphorylation of perfluoroalkylated rac-di-O-alk(en)ylgly-cerols using POCl3, then condensation with choline tosylate or N-Boc-ethanolamine (2-[(tert-butoxy)carbonyl-amino]ethanol) followed by Boc-deportection (Schemes 6-8). The fluorcarbon/fluorocarbon 1,2-di-O-alkylgly-cerols were prepared by O-alkylation of rac-1-O-benzylglycerol using perfluoroalkylated mesylates, then hydrogenolysis for benzyl deprotection (Scheme 1). The two different hydrophobic chains in the mixed fluorocarbon/fluorocarbon and fluorocarbon/hydrocarbon 1,2-di-O-alk(en)ylglycerols were introduced starting from 1,2-O-iso-propylidene- then O-trityl-protected glycerols or from 1,3-O-benzylidene-glycerol (Schemes 3 and 4). The perfluoroalkylated O-alkenylglycerols were obtained by O-alkylation of a glycerol derivative using an ω-unsaturated alkenyl reagent, the perfluoroalkyl segment being connected onto the double bond in a subsequent step (Schemes 1) and 3. The perfluoroalkylated symmetrical and mixed 1,3-di-O-alkylglycerols were synthesized by displacement of the Cl-atom in epichlorohydrin by perfluoroalkylated alcohols, then catalytic (SnCl4) opening of the oxirane ring of the resulting alkyl glycidyl ethers in neat alcohols (Scheme 5). When injected intravenously into mice, acute maximum tolerated doses higher than 1500 and 2000 mg/kg body weight were observed for the fluorinated glycerophosphocholines, indicating a very promising in vivo tolerance.

Notes: Ten new α-diazo-β-oxoaldehydes were condensed with aniline, ammonia, hydroxylamine, and semicarbazide to yield new 4-acyl-(1-substituted)-1H-1,2,3-triazoles in moderate-to-good yields. The method is simple and regiospecific. The latter feature makes this method superior to the widely used acylacetylene + azide approach.

Notes: The synthesis of oligonucleotides containing N7-(2-deoxy-β-D-erythro-pentofuranosyl)guanine (N7Gd; 1) is described. Compound 1 was prepared by nucleobase-anion glycosylation of 2-amino-6-methoxypurine (5) with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D-erythro-pentofuranosyl chloride (6) followed by detoluoylation and displacement of the MeO group (8→10→1). Upon base protection with the (dimethylamino)methylidene residue (→11) the 4,4-dimethoxytrityl group was introduced at OH—C(5′) (→12). The phosphonate 3 and the phosphoramidite 4 were prepared and used in solid-phase oligonucleotide synthesis. The self-complementary dodecamer d(N7G—C)6 shows sigmoidal melting. The Tm of the duplex is 40°. This demonstrates that guanine residues linked via N(7) of purine to the phosphodiester backbone are able to undergo base pairing with cytosine.

Notes: Starting from the esters (2E,4S)-6 and (2E,4R)-6, bromo aldehydes (S)-9 and (R)-9 as well as bromo alcohols (S)-10 and (R)-10, respectively, were prepared. Bromo alcohol (R)-8 was converted to the diol (2E,4R)-16. Ozonolysis of the latter led to aldehyde (R)-17, which was transformed, by a Wittig reaction, to (2R,4E,6R)-18, corresponding to the C(7)-to-C(14) segment of phomenoic acid (1). Attempts to improve the yields by applying a Julia coupling of (R)-23, which was prepared from (2E,4R)-7, with (R)-24 were unsuccessful. Finally, the coupling of the iodo derivative (2E,4S)-28 with the lithiated derivative of 1,3-dithiane 30 by the Corey-Seebach ‘Umpolung’ led to (3S,4E)-32 which is a derivative of the C(7)-to-C(14) segment of 1, suitable for further transformations.

Notes: Monodisperse and polydisperse oligomers and polymers of 3-hydroxybutanoic acid (3-HB) containing 8, 16, ca. 28, 32, ca. 60, 64, 96, and ca. 3000 monomer units were incorporated into palmitoyl-oleoyl-phosphatidyl choline (POPC) planar bilayers. At concentrations of 0.1-5% of oligo(3-HB), the resulting phospholipid bilayers showed typical single-channel behavior for Rb+ and Ba2+ ions, using the patch clamp technique. Thus, channel-forming activity of a pure polyester has been demonstrated for the first time (Figs. 1, 3, and 6). Single-channel activity depends upon the following structural parameters of the 3-HB derivatives: unprotected OH and COOH groups on the chain ends; chain length ≥ 16 monomer units; no high-molecular-weight as in P(3-HB). The results are discussed in view of the Ca2+-specific channel formed with the P(3-HP)/Ca · PPi complex from genetically competent Escherichia coli and in view of the ubiquitous occurrence of low-molecular-weight P(3-HB) in prokaryotic and eukaryotic organisms. A simple model for the channel-causing structure is proposed, based on the proven tendency of oligo- and poly(3-HB) to form ca. 50-Å thick lamellar crystallites.

Notes: The Synthesis of p-CumaroylspermidinesThe synthesis of three mono[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]spermidines, 10, 20, and 28, three bis[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]spermidines, 6, 16, and 25, and one tris[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]-spermidine is described.

Notes: Four cyclotetrapeptides containing one (1, 2) or two (3, 4) chiral amino acids have been C-alkylated or C-hydroxyalkylated through Li+ or phosphazenium (P4 · H+) enolates. The reactions are completely diastereoselective (by NMR or HPLC analysis) with respect to the newly formed backbone stereogenic centres (Tables 2 and 3). The reactivity of the polylithiated species responsible for these alkylations is such that only highly reactive electrophiles (MeI, BnBr, primary allylic halides, aldehydes, CO2) can be employed. It is shown that the position, and thus the chirality sense, of the newly formed stereogenic centre in a given cyclotetrapeptide backbone is controlled by the positioning of N-methyl groups in the starting material (cf. cyclo(-MeLeu-Gly-D-Ala-Sar-) (3) and cyclo(-Leu-Sar-MeDAla-Gly-) (4) in Scheme 1). With Schwesinger's phosphazene P4-base, all NH groups are first benzylated and C-benzylation then takes place at a sarcosine, rather than an N-benzylglycine residue (Table 3). In contrast to open-chain N-benzyl peptides, the N-benzylated cyclotetrapeptides could not be debenzylated under dissolving-metal conditions (Na/NH3). Conformational analysis (NMR spectroscopy and X-ray diffraction) shows that the prevailing species have cis/trans/cis/trans(ctct) peptide bonds (zigzag conformation of Ci backbone symmetry, Figs. 2-4). However, a hitherto unknown conformation of cyclotetrapeptides has been found in CDCl3 solutions of the hydroxyalkylated products 18-21 (obtained with EtCHO and PhCHO as electrophiles; Fig.4). The new conformation has four trans peptide bonds and is believed to result mainly from intramolecular H-bond formation, involving the newly generated alkyl- or arylserine residue. This assumption has also been supported by modelling (TRIPOS force field, SYBYL, see Fig.5 and Table 6). The structure may be considered as a β-turn mimic.

Notes: The synthesis of functionalized 1,1,2,2-tetraethynylethanes (= 3,4-diethynylhexa-1,5-diynes) as synthons for tetraethynylethenes (3,4-diethynylhex-3-ene-1,5-diynes) and as building blocks for three-dimensional acetylenic molecular scaffolding targeting the synthesis of the molecular carbon belts 3 and 4 is reported (Scheme 1). Reaction of diethyl oxalate and (trialkylsilyl)ethynyl Grignard reagents afforded the silyl-protected 3,4-diethynylhexa-1,5-diyne-3,4- diols 7 and 8 which were transformed in high yields into the cyclic carbonate 9 and the cyclic orthoesters 10-13, respectively (Scheme 2). The solid-state structures of 9 and 10 were elucidated by X-ray crystallography. The alkyne protecting groups in 9, 10, and 12 were smoothly removed to give the free tetraynes 14-16 as relatively stable oils in nearly quantitative yields (Scheme 3). Orthoesters 15 and 16 underwent Pd-catalyzed cross-coupling with iodobenzene to give the tetraphenyl derivatives 17 and 18 (Scheme 4). Thermal acid-catalyzed elimination of the orthoester moieties in 12 and 13 produced the silyl-protected tetraethynylethenes 19 and 20 and concluded a novel, simple three-step synthesis of these fully two-dimensionally conjugated π-chromophores (Scheme 5).

Notes: A series of new carbocyclic C-nucleosides with a cis-4′-(hydroxymethyl)cyclopent-2′-enyl sugar moiety and unnatural pyrimidine bases (2-6) were synthesized in racemic form in two steps starting from the easily accessible cyclic carbonate 1.

Notes: The synthesis and liquid-crystalline and thermal properties of a fullerene[60] functionalized by a framework containing two cholesterol derivatives through a methanofullerene structure are reported. The targeted fullerene derivative showed high thermal stability.

Notes: The synthesis of the thymine- and adenine-containing 5′-epi-bicyclodeoxynucleosides 7 and 8 as well as of the corresponding building blocks 13 and 14 for oligonucleotide syntheis according to the phosphoramidite methodology is described. A conformational analysis of 7 and 8 by 1H-NMR spectroscopy, refined by molecular modeling, shows the preferred conformation of the furanose unit in these nucleosides to be of the 1′-exo/2′-endo type. The 5′-OH group on the carbocyclic ring prefers to be axially oriented, thus placing torsion angle γ in the unusual -syn-clinal (-sc) range. These epi-bicyclodeoxynucleosides were successfully incorporated into DNA decamers. From UV/melting curves of such decamers with DNA and RNA complements, a duplex destabilization of -2 to -9° per residue was observed. An oligonucleotide built completely from 5′-epi-bicyclothymidine shows no detectable affinity to its DNA or RNA complement anymore. CD Spectra of duplexes containing 5′-epi-bicyclodeoxynucleotide units are very similar to the natural reference systems, indicating no major structural changes. A molecular-dynamics simulation of a heptamer duplex containing one 5′-epibicyclothymidine residue in the center reveals a conformational change of its carbocyclic unit placing torsion angle γ in the (for the free mononucleoside unfavorable) -anti-clinal (-ac) conformation in the duplex. The role of torsion angle γ on DNA duplex stability is discussed.

Notes: L-Aspartic acid by tosylation, anhydride formation, and reduction with NaBH4 was converted into (3S)-3-(tosylamino)butan-4-olide (8; Scheme 1). Tretment of 8 with ethanolic trimethylsilyl iodide gave the N-protected deoxy-iodo-β-homoserine ethyl ester 9. The latter, on successive nucleophilic displacement with lithium dialkyl-cuprates ( → 10a-e), alkaline hydrolysis ( → 11a-e), and reductive removal of the tosyl group, produced the corresponding 4-substituted (3R)-3-aminobutanoic acids 12a-e (ee 〉 99%). Electrophilic hydroxylation of 8 ( → 19; Scheme 3), subsequent iodo-esterification ( → 21; Scheme 4), and nucleophilic alkylation and phenylation afforded, after saponification and deprotection, a series of 4-substituted (2S, 3R)-3-amino-2-hydroxybutanoic acids 24 including the N-terminal acids 24e ( =3) and 24f ( =4) of bestatin and microginin (de 〉 95%), respectively.

Notes: An asymmetric synthesis of the spermidine alkaloid (+)-cyclocelabenzine (1a) and its (-)-(13S)-epimer 1b is described using optically active (+)-(3S)-3-amino-3-phenylpropionic acid as the chiral building block. The isoquinolin-1-one fragment 15 was synthesized by a modified Bischler-Napieralski reaction. The relative configuration of the (-)-isomer was determined by an X-ray crystal-structure analysis, which enabled us to determine the absolute configuration of natural (+)-1a as (8S,13R).

Notes: The methanolysis of the epimeric 7-chloro-7H-yohimbine derivatives 2 and 3 was reinvestigated. In case of the 7α-epimer 2, the reaction was uneventful and conformed with earlier observations, i.e., under sufficiently mild conditions, only the imino ether 4 (= imino ether A) was produced. Under the same conditions, the less reactive β-isomer 3 furnished a mixture of both imino ethers 4 and 5, accompanied by the elimination product 11, and by equal amounts of yohimbine (1) and 3,4,5,6-tetradehydroyohimbine (12), which are believed to arise through a disproportionation process of the putative intermediate 5,6-didehydroyhimbine (23). The nature of this divergent reactivity and of the ready equilibration of 4 and 5 was investigated by means of extensive force-field and semi-empirical calculations (AM1 and PM3) of various conformers of the compounds 2-5 and of some possible reaction intermediates.

Notes: 2-Alkynylcyclohex-2-enones 1a-c and 2a-c react with H2O2/NaOH in MeOH to afford 1-alkynyl-7-oxabicyclo[4.1.0]heptan-2-ones 3a-c and 4a-c, respectively. The 3-unsubstituted bicyclic epoxy ketones 3a, 3b, and 4a, 4b react further with H2O2/NaOH, undergoing ring contraction and (formal) decarbonylation to give 2-alkynylcy-clopent-2-enols 5a, 5b, and 6a, 6b, respectively. Epoxy ketones 3 are also obtained under neutral conditions on irradiation (λ = 350 nm) of cyclohexenones 1 in air-saturated benzene solution. Similarly, under neutral conditions oxo-cycloalkenecarbonitriles 8 react (thermally) with H2O2 in MeCN to give the oxabicyclic carbonitriles 9.

Notes: Oligonucleotides containing (2′-deoxy-β-D-xylofuranosyl)guanine have been prepared. For this purpose 2-aminoadenosine (5) was synthesized and converted to 2′-deoxy-β-D-xyloguanosine (1). The related 2′-deoxy-β-D-xyloisoguanosine (3) and 2′-deoxy-β-D-xyloxanthosine (4) were also synthesized. Compound 1 was converted to the phosphonate and phosphoramidite building blocks 10 and 11, respectively. The oligodeoxynucleotide (5′-3′)d(xG-xT-xA-xG-xA-xA-xT-xT-xC-xT-xA-xC-T) (18) formed a duplex with the same Tm as the parent (5′-3′)-(G-T-A-G-A-A-T-T-C-T-A-C) (19), but with an inverted CD spectrum.

Notes: Early steps in the biosynthesis of dedecano-4-lactone in ripening nectarines (Prunus persica var. nucipersica) and strawberries (Fragaria ananassa) were studied using cis-9,10-([18O]epoxy)heptadecanoic acid (5), instead of the natural C18-precursor epoxystearic acid 1. In nectarines, an epoxide hydrolase catalyzed, in a highly regio- and enantioselective reaction, the attack of H2O at C(9) of epoxy acid 5 yielding preferentially (9R,10R)-dihydroxyheptadecanoic acid 6a as an early intermediate and, after further metabolization, undecano-4-lactone 7a. In strawberries, the same transformation exhibited only a moderate regio- and enantioselectivity. Besides the previously established function of phytogenic epoxide hydrolases involved in generating oxygenated fatty-acid derivatives, which are used in cutin monomer production and plant defence, a new rǒle for these enzymes now emerges in the enantioselective production of aroma components of ripening fruits. The cis-9,10-([18O]epoxy)heptadecanoic acid (≥ 98% 18O; 5) was obtained in good overall yield (68%) from isopropyl (9Z)-heptadec-9-enoate using 18O2 gas in a free-radical chain reaction in the presence of 2-methylbutanal.

Notes: Synthesis of Trifluoromethyl-Substituted Sulfur Heterocycles Using 3,3,3-Trifluoropyruvic-Acid DerivativesThe reaction of methyl 3,3,3-trifluoropyruvate (1) with 2,5-dihydro-1,3,4-thiadiazoles 4a, b in benzene at 45° yielded the corresponding methyl 5-(trifluoromethyl)-1,3-oxathiolane-5-carboxylates 5a, b (Scheme 1) via a regioselective 1,3-dipolar cycloaddition of an intermediate ‘thiocarbonyl ylide’ of type 3. With methyl pyruvate, 4a reacted similarly to give 6 in good yield. Methyl 2-diazo-3,3,3-trifluoropropanoate (2) and thiobenzophenone (7a) in toluene underwent a reaction at 50°; the only product detected in the reaction mixture was thiirane 8a (Scheme 2). With the less reactive thiocarbonyl compounds 9H-xanthene-9-thione (7b) and 9H-thioxanthene-9-thione (7c) as well as with 1,3-thiazole-5(4H)-thione 12, diazo compound 2 reacted only in the presence of catalytic amounts of Rh2(OAc)4. In the cases of 7a and 7b, thiiranes 8b and 8c, respectively, were the sole products (Scheme 3). The crystal struture of 8c has been established by X-ray crystallography (Fig.). In the reaction with 12, desulfurization of the primarily formed thiirane 14 gave the methyl 3,3,3-trifluoro-2-(4,5-dihydro-1,3-thiazol-5-ylidene)propanoates (E)-and (Z)-15 (Scheme 4). A mechanism of the Rh-catalyzed reaction via a carbene addition to the thiocarbonyl S-atom is proposed in Scheme 5.

Notes: The oligonucleotide building blocks, the phosphonates 1a, b and the phosphoramidites 2a, b derived from 7-iodo- and 7-bromo-7-deaza-2′-deoxyguanosines 3a, b were prepared. They were employed in solid-phase oligonucleotide synthesis of the alternating octamers d(Br7c7G-C)4 (8) and d(I7c7G-C)4 (9) as well as the homo-oligonucleotides d[(Br7c7G)5-G] (11) and d[(I7c7G)5-G] (12). The melting profiles and CD spectra of oligonucleotide duplexes were measured. The Tm values as well as the thermodynamic data were determined and correlated to the major-groove modification of this DNA. The self-complementary octamers 8 and 9 form more stable duplexes compared to the parent oligomer d(G-C)4. The heteroduplex of d[(I7c7G)5-G] (12) with d(C6) is slightly destabilized (ΔTm = -12°) over that of d[(c7G)5-G] with d(C6). However, the complex of 12 with poly(C) is more stable than that of d[(c7G5-G)] with poly(C).

Notes: The molecular structure of the two complex ions [Co(tmen)3]3+ and [Co(tmen)3]2+ (tmen = 2,3-dimethylbutane-2,3-diamine) have been determined at 100 K. They show a strong trigonal distortion of the octahedral CoN6 core. The twist angle is 26.2(2.8)° for CoII and 43.9(9)° for CoIII. Average Co—N distances are 2.193(13) Å (CoII) and 1.997(2) Å (CoIII), 0.02 Å longer than for the main body of CoIII amines.

Notes: Guanidinium compounds imitating the bis(arginine) structural motif of staphylococcal nuclease (e.g. 3) are known to be powerful catalysts for phosphoryl transfer reactions in dipolar aprotic solvents. Compound 3 also accelerates the hydrolysis of RNA (H2O, pH 7). However, due to diminished substrate affinity in H2O, the rate effects are less pronounced in aqueous than in aprotic solution. To test if a synthetic ribonuclease may be derived from the bis(guanidinium) moiety of 3 by the addition of RNA-binding substructures, the TAR sequence of HIV-1 was chosen as a target. The arginine residue of compound 4 serves as an extremely simplified mimic of tat, a protein responsible for boosting the viral transcription by complex formation with TAR. Here, we present the synthesis of 4 and its ability to bind and to cleave efficiently the truncated TAR sequence 1. In addition, the synthesis of an acridine arginine conjugate, 19, is reported in preliminary form. Compound 19 associates with 1 and completely blocks the cleavage induced by 4.

Notes: Studies on post-angioplastic restenosis have shown the implication of angiotensin II (Ang) as a myoproliferative mediator. The antiproliferative efficacy of non-peptide Ang antagonists on the rat carotid model is of 50%, whereas a continuously infused peptide antagonist at low doses totally blocks neointimal growth. To explore the feasibility of depot forms of Ang that may be introduced during angioplasty and thus prevent restenois, lipid-masked Ang analogues of the following general structure were prepared: [Xxx°, Yyy1]Ang with Xxx = decanoyl or palmitoyl and Yyy = Ser, Cys, Asp, β-lactoyl, 3-mercaptopropanoyl or succinyl. All fatty acylated peptides [Xxx°, Yyy1]Ang were practically inactive, and O- or S-esterified Ser and Cys peptides underwent intramolecular transcylation giving inactive Nx-acylated peptides. O-Acylated [β-mercaptopropanoyl1]Ang were easily hydrolyzed into their biologically active[Yyy1]Ang forms, either by mild saponification or by lipase activity.

Notes: Nortopsentin D (5), a bis(indole) alkaloid unique for bearing a 2-amino-methylimidazole appendage at the central 1H-imidazol-5(4H)-one nucleus, was isolated in abundance, besides the putative biogenetic precursor 6 of its appendage, from the deep-water axinellid sponge Dragmacidon sp. Structural elucidation of 5 by NMR and MS methods heavily relied on its N-methyl derivatives 8-11. Unusually for topsentin-type structures, natural 5 and semisynthetic methyl derivatives 8 and 10 proved inactive on KB tumoural cells, while introduction of the last three methyl groups, amazingly led to highly cytotoxic 11.

Notes: The interaction between a vitamin B12 derivative containing a peripheral C18 alkyl chain (see 1a) and a (methyl)thiomalonate substrate bearing alkyl chains of various length at the thioester group (see 5) was investigated. A catalytic cycle was established for the methylmalonyl→succinyl rearrangement by using electrochemistry and photolysis (see Scheme 3). Increased yields of the succinate relative to the reduction product were obtained (2:3 ratio), when the reaction was run in MeOH/H2O, and when both the substrate and the catalyst had an octadecyl substituent capable of hydrophobic interactions.

Notes: The electrospray tandem mass spectra (ESI-MS/MS) of the three N,N′-bis[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]spermidines 1-3 displayed the same fragment-ion signals. These isomers could not be differentiated by ESI-MS/MS, since their fragmentation patterns are similar. (E,E)-N-(3-[15N]Aminopropyl)-3,3′-bis(4- hydroxyphenyl)-N,N′-(butane-1,4-diyl)bis[prop-2-enamide] ([15N(1)])-(1) was synthesized in order to get further information about the fragmentation mechanisms. The comparison of the ESI-MS/MS of 1 and [15N(1)]-1 revealed a transamidation, the Zip reaction, under mass-spectral conditions of the [1 + H]+ ions. Because of this reaction, the three isomers 1-3 could not be distinguished.

Notes: A total synthesis of cyclothialidine (1), a new DNA gyrase inhibitor isolated from Streptomyces filipinensis, is described. The synthetic concept was tested by preparing the lactone 13 (Scheme 2) which contains the characteristic bicyclic core entity of 1. Key features of the synthesis of 1 are: preparation of 3,5-dihydroxy-2,6-dimethylbenzoic acid (23) from 3,5-dihydroxybenzoic acid (19) by two consecutive Mannich aminomethylation/hydrogenation sequences; benzylic N-bromosuccinimide bromination of an ester derivative 25 thereof and its subsequent coupling with Boc-Ser-Cys-OMe (11); cyclization of the ω-hydroxy acid 29 29 to the 12-membered lactone 30 using preferably Mitsunobu conditions; completion of the peptidic side chains of 1 using Boc strategy (Scheme 4). Optically pure cis-N-(tert-butoxycarbonyl)-3-hydroxy-L-proline ((-)-14) was obtained by resolution of the racemate via an efficient reaction sequence containing a lipase-catalyzed enantiospecific acetate hydrolysis (Scheme 3). The structure of natural 1 was confirmed by comparison with the synthetic material. The synthetic route described provides also easy access to analogues of 1, e.g., via the intermediate 30.

Notes: A comprehensive series of tetraethynylethenes (= 3,4-diethynylhex-3-ene-1,5-diynes, TEEs) bearing electrondonating (p-methoxyphenyl or p-aminophenyl) and/or electron-accepting (p-nitrophenyl) groups was prepared via [Pd]-catalyzed Sonogashira cross-coupling reactions. The electronic and photonic properties of these molecules were investigated with a special emphasis on the effects caused by degree and pattern of donor/acceptor substitution around the central TEE core. This analysis showed that intramolecular donor-acceptor interactions, as evidenced by a long-wavelength charge-transfer band, are considerably more effective in TEEs 44 and 46, with trans and cis, linearly-conjugated electronic pathways between donor and acceptor, than in 11, with a geminal, cross-conjugated electronic pathway. UV/VIS Spectroscopy revealed a steady bathochromic shift of the longest-wavelength absorption band (λmax) as the number of donor-acceptor conjugation paths increased upon changing from bis-arylated (11, 44, and 46) to tetrakis-arylated (14, 31, and 35) TEEs. The position of the longest-wavelength absorption was also found to be strongly dependent on the nature of the N-substituents in the R2NC6H4-donor groups. Electronic emission spectroscopic investigations demonstrated a considerable solvent dependency of the fluorescence of donor-acceptor-substituted TEEs such as 11 or 44, in agreement with the presence of highly polarized excited states in these molecules. Correspondingly, fluorescence spectra of TEEs bearing only donor or acceptor substituents showed little solvent dependency. The large majority of the donor/acceptor-substituted TEEs are thermally and environmentally stable molecules. They can be stored for months as solids in the air at room temperature, and many decompose only upon heating to temperatures above 200°. X-Ray analysis showed the conjugated C-atom scaffolds of 44, 46, and 67 to be essentially planar, whereas the aryl substituents in 28 and 30 are rotated out of the plane of the TEE core by varying degrees.

Notes: The β-hexapeptide (H-β-HVal-β-HAla-β-HLeu)2-OH (2) was prepared from the component L-β-amino acids by conventional peptide synthesis, including fragment coupling. A cyclo-β-tri- and a cyclo-β-hexapeptide were also prepared. The β-amino acids were obtained from α-amino acids by Arndt-Eistert homologation. All reactions leading to the β-peptides occur smoothly and in high yields. The β-peptides were characterized by their CD and NMR spectra (COSY, ROESY, TOCSY, and NOE-restricted modelling), and by an X-ray crystal-structure analysis. β-Sheet-type structures (in the solid state) and a compact, left-handed or (M) 31 helix of 5-Å pitch (in solution) were discovered. Comparison with the analogous secondary structures of α-peptides shows fundamental differences, the most surprising one at this point being the greater stability of β-peptide helices. There are structural relationships of β-peptides with oligomers of β-hydroxyalkanoic acids, and dissimilarities between the two classes of compounds are a demonstration of the power of H-bonding. The β-hexapeptide 2 is stable to cleavage by pepsin at pH 2 in H2O for at least 60 h at 37°, while the corresponding α-peptide H-(Val-Ala-Leu)2-OH is cleaved instantaneously under these conditions. The implication of the described results are discussed.

Notes: Cholic-acid-type 3-keto steroids 1-8, all isolated from Deltocyathus magnificus (2-8 after CH2N2 treatment), are the first secondary metabolites obtained from a deep-water scleractinian. Steroids 1-3, 5, and 7 are new, their main structural oddities being loss of C(24) (see 5) or hydroxylation in the side chain (see 3 and 7). Steroids 4, 6, and 8, from the same coral, were previously known from other marine organisms.

Notes: Rearrangement of 5α- and 5β-cholesta-6,8(14)-dienes (13a and 13b, resp.) in the presence of anhydrous toluene-4-sulfonic acid in acetic acid leads to 5α- and 5β-12(13 → 14)-abeo-cholesta-8,13(17)-dienes (15a and 15b, resp.) via 5α- and 5β-cholesta-8,14-dienes (14a and 14b, resp.), respectively. Epimerization at C(20) of the spirosteradienes 15a and 15b occurs with increasing reaction time. Molecular-mechanics calculation of the relative stabilities of these compounds and of congeners thereof is in agreement with the observed reaction pathway.

Notes: The total syntheses of the spermidine alkaloids (-)-mayfoline (11) and (+)-N(1)-acetyl-N(1)-deoxymayfoline (12) are described. These macrocyclic lactams belong to the most interesting conjugates of the polyamine derivatives very commonly found in nature. The enantioselective syntheses were achieved through resolution of the methyl 3-amino-3-phenylpropanoate (2) by recrystallization of its (+)-L-tartrate salt. Construction of the 13-membered ring ensued through condensation, reductive ring expansion (internal bond cleavage), and finally a transamidation reaction involving a second ring expansion.

Notes: A number of natural polyphenols (chlorogenic acid (9), cordigol (11), cordigone (12), danthrone (1), 1,5-dihydroxy-3-methoxyxanthone (2), eriosematin (7), flemichin D (8), frutinone A (6), mangiferin (4), quercetin (5), 1,3,6,7-tetrahydroxyxanthone (3) and verbascoside (10)) were investigated for their redox properties using cyclic voltammetry. The antioxidant properties of these compounds were also examined in two models, namely lipid peroxidation in rat synaptosomes and AAPH-mediated oxidation of serum albumin. Compounds with a catechol group (9, 4, 5, 3 and 10) were oxidized below 0.4 V and inhibited lipid peroxidation with IC50 values between 2 and 8 μM. Compounds having one or more isolated phenolic groups and showing an oxidation potential between 0.45 and 0.8 V (11, 12 and 8) inhibited lipid peroxidation with IC50 between 7 and 9 μM, except 2 (0.45 V), danthrone (0.96 V) and eriosematin which showed no or modest antioxidant activity. Some of the investigated compounds also protected albumin from oxidation, but no structure-activity relationship was apparent, suggesting that other factors beside redox potential influence this activity.

Notes: To demonstrate the relevance of the kinetic acidity of individual OH groups for the regioselectivity of glycosylation by glycosylidene carbenes, we compared the glycosylation by 1 of the known triol 2 with the glycosylation of the diol D-3 and the fluorodiol L-4. Deoxygenation with Bu3SnH of the phenoxythiocarbonyl derivative of 5 (Scheme 1) or the carbonothioate 6 gave the racemic alcohol (±)-7. The enantiomers were separated via the allophanates 9a and 9b, and desilylated to the deoxydiols D- and L-3, respectively. The assignment of their absolute configuration is based upon the CD spectra of the bis(4-bromobenzoates) D- and L-10. The (+)-(R)-1-phenylethylcarbamates 13a and 13b (Scheme 2) were prepared from the fluoroinositol (±)-11 via (±)-4 and the silyl ether (±)-12 and separated by chromatography. The absolute configuration of 13a was established by X-ray analysis. Decarbamoylation of 13a ( → L-12) and desilylation afforded the fluorodiol L-4. The H-bonds of D-3 and L-4 in chlorinated solvents and in dioxane were studied by IR and 1H-NMR spectroscopy (Fig. 2). In both diols, HO—C(2) forms an intramolecular, bifurcated H-bond. There is an intramolecular H-bond between HO—C(6) and F in solutions of L-4 in CH2Cl2, but not in 1,4-dioxane; the solubility of L-4 in CH2Cl2 is too low to permit a meaningful glycosidation in this solvent. Glycosidation of D-3 in dioxane by the carbene derived from 1 (Scheme 3) followed by acetylation gave predominantly the pseudodisaccharides 18/19 (38%), derived from glycosidation of the axial OH group besides the pseudodisaccharides 16/17 (13%) and the epoxides 20/21 (7%), derived from protonation of the carbene by the equatorial OH group. Similarly, the reaction of L-4 with 1 (Scheme 4) led to the pseudodisaccharides 28/29 (46%) and 26/27 (14%), derived from deprotonation of the axial and equatorial OH groups, respectively. Formation of the epoxides involved deprotonation of the intramolecularly H-bonded tautomer, followed by intramolecular alkylation, elimination, and substitution (Scheme 4). The regio- and diastereoselectivities of the glycosidation correlate with the H-bonds in the starting diols.

Notes: Using the chiral triazolium salt 1 as catalyst, a novel asymmetric variant of the benzoin reaction is reported. For the first time, the scope of the method is extended to a broader range of aromatic aldehydes 2, affording the acyloins 3a-h in yields of 22-72% and enantiomeric excesses up to 86%.

Notes: Ninety years ago, chemical methods were used in solving biological problems. In our days, methods of evolutionary biology are going to be used in solving problems of synthetic chemistry.

Notes: The cellobiose-derived dialkynes 14 and 15 were prepared by glycosidation of the acceptor 9 with the thioglycosides 12(82%) and 13(85%), respectively. The acceptor 9 was prepared from the known alcohol 2 via the lactone 7 in five steps (48% overall), and the donors 12 and 13 were prepared from the alkynylated anhydroglucose derivative 10 (60% overall). Acetolytic debenzylation of 14 and 15 (→16 and 17, resp.) followed by deacylation of 16 yielded 60% of the cellobiose-derived dialkyne 18. Deacylation of 14 (→19), methoxymethylation (→20) and trimethylgermylation led to the orthogonally protected dialkyne 21 (69% overall). Protodesilylation of 21 with K2CO3/MeOH gave 22 (90%), while the Me3Ge group was selectively removed with CuBr (19 mol-%) in THF/MeOH to give 20 (95%). Treatment of 21 with aqueous HCl solution led to 19 (80%). Bromodegermylation of 21 (NBS/AgOOCCF3) led to a mixture of 23 (85%) and 24 (11%). Similar conditions using CuBr instead of AgOOCCF3 gave exclusively the bromoalkyne 23 (93%). The temperature dependence of the δ values of the OH resonances of 18 in (D6)DMSO evidence a strong intramolecular H-bond between C(5′)—O…HO—C(5).

Notes: The Cinchona alkaloid analogs (+)- and (-)-5 with a quinuclidine-2-methanol residue attached to C(2) of a 9,9′-spirobifluorene moiety were prepared as a racemic mixture by reacting lithiated 2-bromo-9,9′-spirobifluorene 7 with (2-ethoxycarbonyl)quinuclidine (±)-6 to give ketone (±)-8, followed by diastereoselective reduction with diisobutylaluminum hydride (DIBAL-H). The absolute configuration at C(9) and C(8), i.e., at the methanol bridge and the adjacent quinuclidine C-atom, in the two enantiomers of 5 is identical to the configuration at the corresponding centers in (-)-quinine (1) and (+)-quinidine (2), respectively. For the optical resolution of (±)-5, a chiral stationary phase for HPLC was prepared by covalently bonding quinine via a thiol spacer to a silica-gel surface. The enantiomer separation was accomplished at an α value of 1.61 with (±)-5 being eluted last, in agreement with 1H-NMR studies in CDCl3 which showed that (+)-5 underwent a more stable host-guest association with quinine than (-)-5. 1H{1H} Nuclear Overhauser effect (NOE) difference spectroscopical analysis of the host-guest associations with quinine in CDCl3, combined with computer-model examinations, allowed the assignment of the absolute configurations as (+)-(8R,9S)-5 and (-)-(8S,9R)-5. A detailed conformational analysis displayed excellent agreement between the results of computational methods (Monte Carlo multiple minimum simulations, analyses of the total energy as a function of the flexible dihedral angles in the molecule) and 1H{1H}-NOE difference spectroscopical data. It was found that (-)-5 and (+)-5 differ significantly in their conformational preference from their natural counterparts quinine (1) and quinidine (2). Whereas the natural alkaloids prefer the ‘open’ conformation, with the quinuclidine N-atom pointing away from the quinoline ring, analog (±)-5 adopts preferentially (by ca. 4 kcal mol-1) a ‘closed’ conformation, in which the quinuclidine N-atom points into the cleft of the 9,9′-spirobifluorene moiety. Since the basic quinuclidine N-atom in the ‘closed’ conformation is sterically shielded from forming strong H-bonds, the new Cinchona alkaloid analogs form less stable host-guest associations via H-bonding than quinine or quinidine.

Notes: Acidic condensation of 2,4-dimethylfuran with acetaldehyde provided 2,2′-ethylidenebis[3,5-dimethylfuran] (7) which added 1 equiv. of methyl bromopropynoate to give a major adduct 8. Regio- and stereoselective hydroboration of the latter 7-oxanorbornadiene derivative followed by alcohol protection and methanolysis of its β-bromoacrylate moiety gave (1RS,2RS,4RS,5SR,6SR,1′RS)-methyl 4-[1′-(3″,5″-dimethylfuran-2″-yl)ethyl]-3,3-dimethoxy-6-exo-[(2-methoxy)ethoxy]-1,5-endo-dimethyl-7-oxabicyclo[2.2.1]heptane-2-endo-carboxylate (24) (Schemes 2 and 3). Reduction of 24 with LiAlH4, followed by H2O and MeOH elimination gave the 3-methyl-idene-7-oxanorbornan-2-one derivative 26 which underwent 7-oxa ring opening through a SN2′ type of reaction with Me2CuLi (Scheme 4). Stereoselective hydrogenation and ketone reduction provided (1RS, 2SR,3RS,4RS,5RS,6RS,1′SR)-1- [1″-(3 ″,5″-dimethylfuran-2″-yl)]-c-3-ethyl-c-5-[(2-methoxyethoxy)m e-c-ethyl-c-c-5-(2-methoxyethoxy)methoxy]-t-4,t-6-dimethyl-cyclohexane-r-1,c-2-diol (32), the oxidative cleavage of which with Pb(OAc)4 generated a 6-oxo-aldehyde 33 (Schemes 4 and 5). Chemoselective protection of 33 and chemo- and stereoselective reductions generated (2RS,3RS,4SR,5SR,6SR,7RS)-7-(3′,5″-dimethylfuran-2′-yl)-2-ethyl-6-hydroxy-4-[(2-methoxyethoxy)methoxy]-3,5-dimethyloct-1-yl pivaloate (36) and its 4-hydroxy 6-epimer 40 (12 and 13 steps, resp., from adduct 8; Scheme 5). Oxidation of the furan ring of 36 led to a (2RS,3SR,4RS,5SR,6RS,7RS)-7-ethyl-3,5,8-trihydroxy-2,4,6-trimethyl-octanoic acid derivative 44, a polypropionate fragment with six contiguous stereogenic centres (Scheme 6).

Notes: Isomerization of (all-E)-Cycloviolaxanthin. Preparation and Characterization of (9Z)- and (13Z)-CycloviolaxanthinFrom (all-E)-cycloviolaxanthin (ex Capsicum annuum), (9Z)- and (13Z)-cycloviolaxanthin were prepared in a highly pure state. The configuration of both isomers was determined by means of UV/VIS, NMR, and CD spectroscopy.

Notes: Cyclohexa-1,3-dienes 7-10 with a 1,5,6-substitution pattern were prepared in a one-pot reaction sequence by sequential addition of MeLi and propargyl bromides to the tricarbonylchromium complex 1a. These products were subjected to radical cyclization procedures. Vinyl radical generation by Bu3Sn addition to the propargyl group in 7-10 was followed by regio- and diastereoselective intramolecular ring closure. Two different 5-exo-trig cyclizations are possible via different vinyl radical intermediates and cyclization to one or the other of the termini of the cyclohexadiene moiety. Internal alkynes reacted to yield exclusively the cis-fused hexahydroindene products 12-14, whereas the terminal alkyne yielded bicyclo[3.2.1]octenes 11 as sole products.

Notes: The first asymmetric intramolecular Stetter reaction is reported, using the chiral triazolium salt 1 as catalyst. Starting from the easily accessible 4-(2-formylphenoxy)but-2-enoates 2, this protocol opens up an enantioselective pathway to the benzo-annulated pyran-4-ones (chroman-4-ones) 3a-h with good yields and enantiomeric excesses of up to 74%.

Notes: The 3-(2-propenylidene)-β-lactams 1a-c react as semicyclic dienes with the dihydrotriazole-diones 2 in a stereoselective fashion leading to the cycloadducts 3. The 3′,3′-disubstituted derivative 4 gives no [4 + 2]-cycloaddition products but forms the adducts 5 and 6. Sterochemistry and reaction pathways are discussed.

Notes: Quantum-chemical calculations employing a density-functional theory/Hartree-Fock hybrid method (B3LYP) have been used to explore the mechanistic details of the C—C and C—H bond-activation processes in propane mediated by a bare Fe+ ion. While the theoretically predicted results are in complete accord with all available experimental data, they give rise to a different mechanistic picture than envisaged previously. In contrast to earlier speculation, the activation barriers for the initial insertion steps of Fe+ into a C—H or C—C bond are found to be significantly below the Fe+ + C3H8 channel. The rate-determining steps for both, the C—C and the C—H bond activation branches of the [FeC3H8]+ potential-energy surface rather occur late on the respective reaction coordinates and are connected with saddle points of concerted rearrangement processes. The C—C bond activation, which leads to the exothermic reductive elimination of methane, occurs via the C—C inserted species and not as a side channel originating from a C—H inserted ion, as assumed hitherto. For the C—H bond-activation processes, which finally results in the exothermic expulsion of molecular hydrogen, two energetically similar reaction channels for an [1,2]-elimination exist. The results clearly show, that an [1,3]-H2-elimination mechanism cannot compete with the [1,2]-elimination paths, in line with the experimental findings. Overall, a lower energy demand for the reductive elimination of methane compared to the loss of H2 is obtained, straightforwardly explaining the preference of the former process observed experimentally.