ALBERT

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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).

Notizen: 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.

Notizen: 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.

Notizen: 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.

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

Notizen: 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.

Notizen: 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.

Notizen: 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).

Notizen: 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).

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

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

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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-|.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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.

Notizen: 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).

Notizen: Absolute configuration of the 3,5-diaminohexanoic acid produced in the β-lysine mutase reactionThe (3S, 5S)-configuration of the 3,5-diaminohexanoic acid 3 produced by the coenzyme-B12-dependent β-lysine mutase from Clostridium sticklandii has been determined by two different methods: by comparison of the 1H-NMR.-spectrum of its δ-lactam with that of synthetic (±)-cis-and (±)-trans-4-amino-6-methyl-piperidones (1 and 2) and by chemical correlation with (+)-(6S)-6-methyl-piperidone-2 (9).

Notizen: A (3-mercapto-1-succinyl)-TMV ∊-maleimidohexanoyl-[1-asparagine, 5-valine]-angiotensin II conjugate was prepared and used for cooperative affinity labeling of bovine adrenal cortex cell membrane vesicles containing angiotensin-binding sites. The labeling was demonstrated by electron microscopy and by CsCl and sucrose density gradient centrifugation Preliminary evidence for specific binding and for the postulated cooperative affinity interaction is produced.

Notizen: The stereochemistry of trans- and cis-2, 4-dimethyl-tetrahydroquinolines, 6 and 7 were derived from 1H-NMR. studies. These were converted respectively into trans- and cis-5, 6-dihydro-4, 6-dimethyl-4H, 8H-pyrido [3, 2, 1-de]phenanthridin-8-ones 18 and 20 by a Pschorr reaction on the anthranilamides 10 and 15. Bromophenanthridones 19 and 21 were similarly prepared from bromoanthranilamides 12 and 17. Detailed 1H-NMR. studies on 18 and 20 indicated axial disposition of the methyl groups at C(2) in both compounds in contrast to the situation in 6 and 7. This is presumably to avoid adverse CH3CO group interaction of the A (1, 3) type. The severity of this is gauged by the preference of 20 for a normally forbidding 1, 3-diaxial orientation of two methyl groups. X-ray crystallographic studies on 19 and 20 confirm the stereochemical assignments.

Notizen: The use of tobacco mosaic virus (TMV) covalently loaded with hormones or other small molecules for various purposes including receptor detection and isolation is proposed. The basic principle is that of cooperative affinity interactions involving (large) numbers of artificially introduced sites (e.g. hormones) of the modified virus on the one hand and membrane-bound sites (e.g. receptors) of a cell or of a cellmembrane particle on the other. In order to test the feasibility of such TMV/hormone conjugates, TMV carrying about 500 molecules of a biologically active α-melanotropin analogue was synthesized, and characterized by its aspect under the electron microscope, by its infectivity, its melanophore-stimulating activity, and its reaction with antisera against α-melanotropin. The observed hormonal activity is in accordance with the idea of cooperative affinity interactions.

Notizen: 5, 7-Dihydroxy-8-methoxy-chroman-4-one from the Bulb Wax of Eucomis comosaFrom the bulb wax of Eucomis comosa (HOUTT.) WEHRH. (Liliaceae) 5, 7-dihydroxy-8-methoxy-chroman-4-one (1) was isolated. The structure was confirmed by direct comparison with a synthetic specimen. 1 is the first natural chroman-4-one which is unsubstituted in the heterocyclic ring.

Notizen: Several long chain primary alcohols (saturated, monoolefinic and methyl branched) have been converted via their mesylates into various long chain alkylated aromatic compounds with basic character, and their mass spectra compared. The spectra of 2-alkylaminopyridines and to some extent those of 3-alkylaminopyridines exhibit most clearly the structure of the aliphatic chain, allowing the localization of branchings and double bonds.

Notizen: The title compounds 14-16 were obtained via an intramolecular Mannich condensation by treating 11-13 with CH2O at RT. The unsaturated ketones 14 and 15 were reduced to the allylic alcohols 18 and 19 respectively. Ring cleavage of compound 18 on treatment with 2N HCl gave the substituted aminopropanol 20. The allylic alcohols 18 and 19 were hydrogenated to 22 and 23 respectively. With CH2O, the amino-alcohol 23 gave the methano-naphthoxazocine 24, whereas 22 and 23, on heating in polyphosphoric acid (PPA), afforded the naphthazepines 25 and 26 respectively. With organolithium compounds, the unsaturated ketones 14 and 16 gave the teriary allylic alcohols 27-29, which were hydrogenated and dehydrated to the olefins 36-40; these were cyclized via an intramolecular alkylation to the methanodibenzo-octahydrocyclooctapyridines 41-43. On heating in PPA, the allylic alcohol 29 was converted into the naphthazepine 44. With CH2O, the naphthol 49 gave the naphthoxazocine 50, in equilibrium with the spiro-naphthalene-pyrrolidinone 51 in solution. Finally, in the presence of CH2O, the naphthazepine 57 afforded the methano-naphthazepinone 58, which, by a 4-stage degradation, was transformed to the benzisoquinoline 62.

Notizen: The dianions of phenanthrene and 1,2,3,4-dibenzocyclooctatetraene have been prepared by metal reduction of the neutral compounds and characterized via the study of their 1H- and 13C-NMR. spectra. A description of the charge distribution can be achieved which is consistent with both MO-models and the spin density distribution of the corresponding radical anions. Thus, the dianion of 1,2,3,4-dibenzocyclooctatetraene appears as a π-bond delocalized species having its excess charge mainly localized in the eight membered ring.

Notizen: An ab initio theoretical study of all fifteen fully staggered conformations of aminodihydroxymethane, CH(OH)2NH2 has been performed. Optimization of the C—O and C—N bond lengths, population analyses and orbital localisation reveal the presence of marked conformation dependent stereoelectronic effects which influence bond lengths and overlap populations. These effects may be parametrized as a function of number and nature of antiperiplanar (app) oriented electronic lone pairs (1p) and polar bonds. In a Y—C—X fragment an app orientation between a lone pair on Y and the C—X bond increases the length and weakens the C—X bond, shortens and strengthens the C—Y bond. Thus a C—X (X = O, N) bond of CH(OH)2NH2 is longest and weakest when: (i) it is app to two vicinal lp's; (ii) the X 1p's are not app to a vicinal polar bond; (iii) the conformation of the molecule has as many axially oriented lp's as possible. Results (i) and (ii) agree with a simple hyperconjugation picture involving interaction between an electronic 1p and an app oriented antibonding bond orbital σ* (C—X). Bond properties, relative energies and effects on reactivity of the tetrahedral species are discussed, as well as their relations to experimental results on the cleavage of tetrahedral intermediates and to enzyme catalysis.

Notizen: Metal reduction of the polycycle 2 yields a surprisingly stable dianion with intact molecular framework. This conclusion can be drawn from reoxidation experiments and from an analysis of the 1H-NMR. spectrum. The excess charge turns out to be distributed over both the π- and σ-fragments of the molecule. The relative stabilities of ionic species derived from 1, 2 and 3 are considered.

Notizen: [2+2]-Cycloadditions and -cycloreversions in radical anions. An ESR. spectroscopic study for 2,2′-disubstituted diphenyl derivativesThe radical anions derived from the polycyclic olefins 1, 2 and 3 are shown by ESR. spectroscopy to undergo [π2+π2]-cycloaddition reactions even at low temperatures. Similarly, facile cleavage by [σ2+σ2]-cycloreversion processes is observed for the radical anions of the corresponding cyclobutane species. This reactivity, which is in marked contrast with the thermal stability of the neutral parent compounds, is discussed taking into account the molecular geometry and the spin density distribution.

Notizen: The 13C- and 17O-chemical shifts of 31 aliphatic ethers are measured and discussed. The 17O-chemical shifts of the ethers ROR′ correlate with chemical shifts for the methylene groups of the corresponding alkanes RCH2R′. The constant of proportionality can be related to the orbital expansion term 〈r-3〉2p. The δc for carbon atoms can also be correlated with δc for the corresponding alkanes. The origin of the correlation is discussed taking into account the conformational modifications resulting from introduction of an oxygen atom in an alkyl chain.

Notizen: Gas liquid chromatography allowed isolation of the novel cis-2-isopropenyl-8-methyl-1,2,3,4-tetrahydro-1-naphthalenol (A) and its dehydration product, 3-isopropenyl-5-methyl-1,2-dihydronaphthalene (B), from two small subfractions of Virginia tobacco condensate. Both these norsesquiterpenes were identified on spectral grounds and synthesized from 1-methylnaphthalene in a way (9 steps) that also afforded the «non-natural», trans-alcohol A′. The possible biogenesis of A and B in tobacco is briefly outlined.

Notizen: The Zip-reaction: A New Method for the Synthesis of Macrocyclic PolyaminolactamsThe 21- and 25-membered aminolactams 11 and 25 were synthesized from the 13-membered lactam 4. To introduce the ring enlargement unit (a propylamino group) 4 was N-alkylated using acrylonitrile and the resulting product hydrogenated. Repetition of this reaction sequence gave 3, which was converted in the presence of base in 90% yield to the ring-enlarged macrocyclic base 11 (Scheme 2). In a similar but stepwise synthesis consisting of two separate ring-enlargement reactions 4 was transformed to 11 via 13 (Scheme 4). Introducing three ringenlargement units into 4 the 25-membered aminolactam 25 was synthesized in 84% yield (Scheme 5). The mechanism of the ring-enlargement reaction is given in Scheme 3. In comparison to a zip-fastener or zipper this reaction is called “zipreaction”.

Notizen: Phytochemistry of genus Gentiana, XXIV. New C-glycosylflavones from the leaves of Gentiana asclepiadea L.p-Hydroxybenzoyl-2″-isoorientin-4′-O-β-D-glucoside (1) was isolated from the leaves of Gentiana asclepiadea L. by means of column chromatography. This is the first occurrence in nature of a p-hydroxybenzoate of isoorientin. p-Hydroxybenzoyl-2″-isoorientin (2) was also shown to be present in the same plant.

Notizen: The structure of vinyl amine and its reactivity towards a proton is studied by the PRDDO SCF MO method. The equilibrium structure is found to be non-planar and barriers to inversion- and rotation-dominated processes are calculated. Proton addition to vinyl amine, as a model of enamine protonation, is examined by means of electrostatic molecular potentials and C- versus N-proton affinities.

Notizen: Electrochemical Formation of Δ1,2-NorborneneThe electrochemical reduction of 1,2-dihalogen norbornanes in tetrahydrofuran/furan leads to a mixture of two isomeric cycloadducts 6 and 7. The ratio of these adducts corresponds to those which have been found in reductive bisdehalogenation of 1 and 2 by butyllithium.

Notizen: The general reactivity of various sites in the vindoline series has been investigated. The facility of electrophilic substitution at C(15) and the effect of steric crowding on reactions at C(4) are discussed. At the basic nitrogen sites, oxidations with mercuric acetate and potassium permanganate are also discussed.

Notizen: Study of the flavonic and xanthonic compounds in the leaves of Gentiana ciliata L.Fifteen 1,3,7,8-oxygenated xanthones (1-15) were isolated from the leaves of Gentiana ciliata L. (genus Gentianopsis). Among these were six new glycosides: glucosyl-1-decussatin 6, glucosyl-1-gentiacaulein (8), primeverosyl-8-isogentiacaulein (9), glucosyl-3-isogentiacaulein (10), glucosyl-1-swertianin (12) and primeverosyl-7-swertianin (13). Three known flavone C-glucosides were also found (16-18).

Notizen: Three kinds of polar substitutent effects are observable in the solvolyses of 1-R-substituted 3-bromoadamantanes (VI). This follows from the relationship between products, rate constants k in 80% ethanol, and the inductive substituent constants σ1q of the substituent R. Alkyl groups and electron-attracting substituents at C (1) control the rate by their inductive effects alone, since logk correlates closely with σ1q. However, rates are higher than predicted on the basis of the respective σ1q values when conjugating (+ M)-substituents or electrofugal groups are attached to C(1). These exalted substituent effects are attributed to CC-hyperconjugative relay of positive charge from the cationic center at C(3) to the substituent at C(1). When the substituent is a strong electron donor (e.g. O- and S-), accelerated substitution gives way to heterolytic fragmentation, rates and products then being controlled by the frangomeric effect.

Notizen: A synthetic model of the active site of the coenzyme B12 dependent methylmalonyl-CoA mutaseThe synthesis of a bridged cobaloxime with a built-in methylmalonic ester moiety is described. 2-Brommethyl-2-methylmalonic acid dichloride (5) afforded upon reaction with 5-heptin-1-ol (4) the corresponding diester 6. Subsequent treatment of 6 with ozone, dimethylsulfide and hydroxylamine hydrochloride led to the pentadentate ligand: 10-brommethyl-10-methyl-9, 11-dioxo-8, 12-dioxa-nonadecane-2, 3, 17, 18-tetraone tetraoxime (8). Reaction of 8 with cobalt (II) chloride, pyridine and sodium borohydride furnished in 7% yield the bridged cobaloxime 10, which was spectroscopically characterized. Short term irradiation of 10 in methanol caused the exchange of the axial pyridine ligand by a solvent molecule affording 10a, the structure of which has been determined by X-ray crystallography. Long term irradiation of 10 in methanol or ethanol led to irreversible cleavage of the Co, C-bond. Upon alkaline hydrolysis the degradation product afforded methylsuccinic acid in 82-95% yield. No incorporation of solvent protons into this product could be observed. Implications of these findings for the mechanism of the coenzyme-B12 catalysed rearrangement of methylmalonyl-CoA are discussed.

Notizen: “Push-Pull” Acetylenes as Reagents for Peptide SynthesisA series of ‘push-pull’ acetylenes 1 is easily available from the corresponding “push-pull” olefins by a simple bromination-dehydrobromination sequence. The versatility of the acetylenes with regard to peptide synthesis is discussed.

Notizen: 1, 4, 5, 6-Tetrahydro-ν-tetrazin-DerivateThe title compounds 2 and 13 are readily available from α-lithiated N-alkyl-nitrosoamines 1 (see Tables 1 and 2) which decompose at - 73° to yield the N-oxides 2. The ESR. spectra of two derivatives 1 are recorded (Fig. 1), and tentative mechanisms are proposed for the head to head dimerizations (la- 3- 4- 5- 2a and Scheme 1). Coupling of lithionitrosoamines with iodine (-6) and alternative decomposition routes of representatives of this class of organometallics with special substitution [equations (2)-(5)] are reported.The structures of the tetrazines are established by spectroscopic data [ESCA] (Fig. 2), IR., UV., 1H- (cf. Fig. 9) and 13C-NMR., PE. (Scheme 2), by an X-ray analysis of 2a (Fig. 4-8 and Table 3), and by the chemical reactions. The crystal structure of 2a is a twisted boat with non planar terminal nitrogen atoms which reflects the electron repulsion in the 4-atom-6-electron N—N=N≡N-system. Comparisons are made with 2-tetrazenes, the open chain analogues of 13, wherever possible. Raney-Ni reductions of 2 or 13 gives diamines 14 to which is assigned the d, l-configuration through the 1H-NMR. spectra of the aminals 7 and 15. Neither the oxides 2 nor the tetrazines 13 undergo cycloaddition reactions [equation (6) and Section 4].Compound 2a is dimerized to the bis (nitrosoamino)-2-tetrazene 18 by treatment with acid, ZnII, CuI or iodomethane. 2a is oxidized at nitrogen to the ethylene diamine derivative 6a (through 20, with H2O2), or at the CH2-groups of the ring to give oxo-N-oxide 21 (with MnO2 or the ring contracted oxo-tetrazoline-N-oxide 22 (with KMnO4).Pyrolysis or photolysis of the dimethyl tetrahydrotetrazine 13a furnishes the trimer 26 of N-methylimine, but no diazetidine 27. Silver and mercury complexes 29 are obtained from 13a, while Cr(CO)5. THF does not furnish a complex as with azocompounds, but rather replaces N2 in 13a by CO (→ 28). Oxidation with permanganate converts 13a into the oxalic acid derivative 30 with unchanged tetrazine structure.

Notizen: A simple one-pot method for esterificationA one-pot procedure for esterifications of primary, secondary and tertiary alcohols and of phenols in high yield is described. Reaction of oxalylchloride with dimethylformamide in a suitable solvent affords dimethylformamide imidechloride; addition of an acid to the suspension of this reagent furnishes an activated carboxy-group derivative, which is then transformed to an ester by addition of pyridine and an alcohol ro a phenol. Reaction temperatures needed for esterification are low, usually 0° to room temperature, reaction times are short.

Notizen: Cyclooct-1-en-5-yne (3) has been obtained as an isolable, but highly reactive hydrocarbon by oxidation of cyclooct-5-ene-1, 2-dihydrazone with lead tetraacetate (Scheme 2). Information regarding the structure and conformational mobility of 3 has been gained from the analysis of its 1H- and 13C-NMR. spectra and was found to agree with the results of force field calculations. Photolysis (206 nm) of 3 in solution has induced cleavage to butatriene and butadiene. The first band in the photoelectron spectrum of 3 (Iv 9.10 eV) is attributed to ionization from a rather delocalized orbital with predominant weight of the double bond p-AO's. Nevertheless, the high reactivity of 3 stems from the strained triple bond as evidenced by the reaction products obtained by pyrolysis, oxidation, Diels-Alder addition, and 1, 3-dipolar addition (Scheme 4).

Notizen: Nucleosides and Nucleotides, Part 11. Phosphorylation of 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1H)-pyridon and its Behaviour in the Synthesis of DinucleotidesThe behaviour of the unnatural nucleoside 1-(2′-deoxy-β-D-ribofuranosyl)-2(1H)-pyridon (Πd, 1) in the synthesis of dinucleotides with purine deoxynucleotides was studied. The optimized preparation of the protected dinucleoside phosphates (MeOTr) Πd pGibd (5) and (MeOTr) Πd pAbzd (7) using the diester method of Khorana with DCC as condensing agent is described. The removal of the N-acyl- and p-methoxytrityl groups was effected by successive treatment with conc. ammonia solution and acetic acid/water 1:1 at 23° yielding the free dinucleoside phosphates ΠdpGd (9) and ΠdpAd (11). In a similar way, starting from (CNEt) pΠd(15), the dinucleotides pΠdpGibd (16), pΠdpGd (18), pΠdpAbzd (17) and pΠdpAd (19) were synthesized.The nucleotide 1-(5′-O-Phosphoryl-2′-deoxy-β-D-ribofuranosyl)-2(1H)-pyridon (pΠd, 3) was prepared in excellent yield by selective phosphorylation of Πd (1) using phosphorylchloride in triethyl phosphate at -40°. Deoxyadenosine was phosphorylated in the same way.The compounds were characterized by UV. spectroscopy, chromatography and enzymatic degradation.

Notizen: In the hydroformylation of 1,1,1-trideuterio-2-butene with Rh4 (CO)12 the deuterated pentanals formed contain 75% of 5,5,5-trideuterio-pentanal, the rest being substantially 2,2-dideuterio-pentanal. On the contrary, using Co2 (CO)8 as the catalyst precursor, position 1 and 4 are formylated to the same extent.

Notizen: The Aminoalkylation of Carbonyl Compounds by the Wittig-ReactionThe Wittig reaction would be a very suitable way to replace the carbonyl group in aldehydes and ketones by a 2-amino-ethylidene group if a simple and convenient method could be devised for synthesizing (2-amino-ethyl)triphenylphosphonium bromides 3. We have synthesized compounds of type like (2-dialkylaminoethyl)-, (2-morpholino-ethyl)-, (2-(1-imidazolyl)ethyl)-, and (2-(1-triazolyl)ethyl)-triphenylphosphonium bromides (cf. Table 1), by melting at 150° the hydrobromides of triphenylphosphine and of the appropriate 2-amino-ethanol. The phosphonium bromides of type 3 could be converted with ketones by the Wittig reaction into the desired amino-ethylidene compounds of type 2, e.g. 18-22 (Table 2). In the case of the reaction with 4-chlorobenzaldehyde the steric course of the transformation was studied, and conditions were found favoring either cis or trans compounds (e.g. 27a or 27b in the reaction of the phosphonium bromide 11, cf. Table 3).

Notizen: Edulon A, a Derivative of 2H-1-Oxapyrene from Plectranthus edulis (LabiataeFrom the coloured leaf-glands of the above mentioned East-african labiate we have isolated Edulon A, A new, deeply coloured diterpenoid. Based mainly on spectroscopic arguments, we propose its structure to be (5a R, 1′ ζ)-10-(2′-acetoxy-1′-methylethyl)-6, 7, 9-trihydroxy-3, 5a-dimethyl-4, 5, 5a, 8-tetrahydro-2H,-l-oxapyrene-2, 8-dione (1a). The compound may be regarded as a 4, 5-seco-abietane derivative that has formed new bonds (between C(18 or 19)—COOH and C(12)—OH), and between C(3) and C (11)) by lactonisation and condensation, respectively.

Notizen: The preparation, crystalline structure, properties and behaviour of the hafnium bis (monohydrogen phosphate) monohydrate as a cationic exchanger have been studied. The crystalline product has been characterized by elemental analysis, X-ray Powder patterns, thermal analysis, photoelectron spectrometry and infra red spectroscopy. A layered structure in which the hafnium and phosphorus atoms are disposed in such a way as to form zeolitic-type cavities is suggested. The reversibility of the exchange with respect to sodium ions is discussed and can be related to the water content of the exchanger.

Notizen: The molluscicidal principle of Cornus florida L. (Cornaceae) has been isolated from the methanolic bark extract by droplet counter-current chromatography (DCC). The structure of the active compounds has been determined as sarsapogenin-O-β-D-xylopyranosyl-(1 → 2)-β-D-galactopyranoside (2) and sarsapogenin-O-β-D-glucopyranosyl-(1 → 2)-β-D-galactopyranoside (3).

Notizen: Radical-induced Intramolecular 1,4-Transfer of a Formyl GroupA further example of a radical-induced intramolecular shift of a functional group in steroids is described. In analogy to the sequence leading to the 1, 4-transfer of cyano groups [3], 11 β-nitrite photolysis was used to generate the appropriate C (18) radical in the 20-hydroxy-11 β-nitrosyloxy-pregnene-21-al 6. Intramolecular addition of the radical center to the double-bond of the specially adjacent aldehyde function, followed by fragmentation of the intermediate cyclic alkoxy radical and subsequent oxidation lead directly to the rearranged 18-formyl compound 10.

Notizen: 3,3,6,9,9-Pentamethyl-2,10-diaza-bicyclo[4.4.0]-1-decen and some of its derivativesA simple synthesis for the bicyclic amidine 1 (Scheme 3) is described. This base and the salts which were prepared from it show solubility characteristics which make the amidine a potentially useful reagent for salt formation of carboxylic acids and related proton complexes of bidentate ligands. Among the derivatives made from 1 are the sterically strongly hindered N-alkylated amidines 11, 12 and 14 (Scheme 5), as well as the stable crystalline N1-oxidoamidine-N2-oxyl radical 2 (Scheme 6). The ability of the latter to serve as a paramagnetic chelating ligand for metal ions is illustrated by the preparation of a corresponding nickel(II) complex. The radical is also a source for the α-nitronyl-nitrosonium cation 4 which shows in its reactivity towards conjugated dienes and olefines some of the expected resemblance to singlet oxygen.

Notizen: The CD. correlation of (3 S, 3′S)-and (3 R, 3′R)-actinioerythrol diacetate, obtained by total synthesis from β-ionone, with actinioerythrin isolated from the sea anemone Actinia equina L. shows that the natural compound has the (3 S, 3′S)-configuration.

Notizen: 3-Substituted 1-iminopyridinium ylides 1 undergo photo-induced ring enlargement to 1H-1,2-diazepines. With strongly electron-withdrawing substituents the ring expansion process is regiospecific and leads exclusively to 4-substituted 1 H-1, 2-diazepines. Weak electron-donating substituents, like a methyl group and halogen atoms, do not have any directing effect since both 4- and 6-substituted 1 H -1,2-diazepines are obtained. With strong electron-donating substituents no diazepines are formed; instead one observes photo-induced isomerization to the 2-aminopyridine derivatives, the process being non-regiospecific. Regiospecific photo-induced ring expansion processes are explained in terms of a simple HMO model.

Notizen: Synthesis of EverninTwo syntheses of the depside evernin 6 are described. Condensation of methyl acetoacetate and methyl crotonate followed by aromatization and reduction with Raney-Ni led to methyl orsellinate (3). The condensation of everninic acid (4), obtained by partial methylation of 3 and saponification of the methyl ester, with methyl 2, 4-dihydroxy-3, 6-dimethylbenzoate (methyl β-orcin carboxylate) (5) in presence of cyclohexylcarbodiimide gave evernin (6). In a second syntheis methyl dihydroorsellinate (1) was regiospecifically converted into its 4-methyl enol ether and aromatized via the benzene selenenyl derivative to yield methyl evernate (7). Benzylation followed by saponification gave the free acid 8. Methyl β-orcin carboxylate (5) was synthesized in an analogous way from methyl 3,6-dimethyl-2,4-dioxocyclohexanecarboxylate. Condensation of 8 with the methyl ester 5 by treatment with trifluoroacetic anhydride in toluene yielded 9, which could be converted into evernin (6) by hydrogenolysis of the benzyl ether.

Notizen: Preparation of styryl derivatives of 3-phenyl-benzisoxazole3-(p-Tolyl)-1,2-or 2, 1-benzisoxazoles and 6-methyl-3-phenyl-1,2-benzisoxazoles react with anils of aromatic aldehydes in the presence of dimethylformamide and potassium hydroxide or potassium t-butoxide to yield the corresponding 3-(stilben-4-yl)-1,2- or 2,1-benzisoxazoles and the 3-phenyl-6-styryl-1,2-benzisoxazoles respectively (‘Anil Synthesis’). Further, the Schiff's bases derived form chloroanilines and 3-(p-formylphenyl)-1,2-benzisoxazoles yield, with methyl-and p-tolyl substituted heterocyles the corresponding heterocyclic substitued styryl and stilbenyl derivatives.

Notizen: Photochemical synthesis of biaryls and heterobiaryls from aryl and heteroarylamines, alkylnitrite and aromatic or heteromatic substratesThe photochemical reaction of aromatic and heteroaromatic amines with excess t-butyl nitrite in aromatic solvents (benzene, p-xylene, mesitylene) and in hetero-aromatic solvents (furan, thiophene) leads to biaryls or heterobiaryls. t-Butyl nitrite is more convenient than isopentyl nitrite which gives by-products. This new method has been used to synthesize 28 compounds in 17 to 60% yield.

Notizen: Studies of Organometallic Compounds. XVII Synthesis of TetracyclohexyltitaniumTetracyclohexyltitanium is prepared by reaction of TiCl4 or Ti(OC4H9)4 with dicyclohexylmagnesium in pentane or ether at - 30°. Some aspects of its reactivity and its decomposition are described.

Notizen: Studies of Organometallic Compounds. XVII: Synthesis and Caracterisation of μ-oxo-bis(dicyclopentadienylmethyltitane IV)(Cp2TiCH3)2O is obtained by reacting (Cp2TiCl)2O with methyllithium. IR., NMR. and MS. spectrum are reported. Autocatalytic decomposition of the product is inferred from differential thermal analytic measurements.

Notizen: The synthesis of sterically hindered 1,1′, 3,3′-tetraethylbenzimidazolotriazatrimethine cyanine dyes, their electron absorption spectra and that of their photo-products (inverse photochromism) is described. Kinetic data of the thermally reversed reaction of the photo-bleached compounds are given. The differences of the electron absorption spectra in this series in this series of dyes are explained by the different degree of distortion of the π-systems which is confirmed by an X-ray investigation.

Notizen: The ESR. spectra of the radical anion and cation of 1, 3, 5-tri-t-butylpentalene (II) have been reexamined under higher resolution. With the assistance of the ENDOR. technique, the coupling constants of all protons in II⊖. and II⊖. could be determined. The experimental data agree satisfactorily with the values predicted by the simple MO model which suggests that the π-spin distributions in II⊖. and II⊖. should not strongly differ from those in the corresponding radical ions of parent pentalene (I). As in the case of other non-alternant hydrocarbons, the proton coupling constants for II⊖. are very sensitive to experimental conditions, due to the association of the radical anion with its counterion. Spectra of II⊖. taken at low temperatures (down to 133 and 163 K for ESR. and ENDOR., respectively) have not revealed specific line-broadening which could arise from the bond shift between the two Kekulé-structures of pentalene.

Notizen: Investigations on the β-lysine mutase reaction: Mechanism and steric courseThe steric course and some mechanistic aspects of the coenzyme-B12-dependent β-lysine-mutase reaction, in which (3 S)-β-lysine is converted to (3 S, 5 S)-3, 5-diaminohexanoate, have been investigated by means of tritium labelling. The reaction involves migration of an hydrogen atom from C(5) of the substrate to C(5′) of coenzyme B12 and back-transfer to C(6) of the product. In the presence of [5′-3H]-coenzyme B12 the enzyme catalyzes the exchange of label between the cofactor and one of the diastereotopic H-atoms at C(5) of the substrate. The exchangeable hydrogen atom is identical with the one specifically involved in the migration reaction. Degradation of the tritiated β-lysine obtained in such experiments yielded a sample of tritiated succinic acid which was shown in an enzymic assay involving partial oxidation with succinate dehydrogenase, to possess the (S)-configuration. Thus, the overall substitution at C(5) occurs with inversion of configuration.

Notizen: Proton hyperfine data have been determined for the radical anions and cations of dibenzo [b,f]pentalene (III) and its 5, 10-dimethyl derivative (IV). The assignment of the coupling constants to pairs of equivalent protons follows from a simple MO model, the use of which enables one to reproduce satisfactorily the experimental values. The proton hyperfine data, aHμThe meaning of aHμis aH—C(x),H—C(y),whereas only x and y are given in the particular cases., for the radical anion III⊖. correlate fairly well with the π-charge populations ∊μ derived from 1H-NMR. spectra for the carbon centres μ in the dianion III2⊖. The analogous correlation is less good in the case of the radical cation III⊕. and the dication III2⊕., presumably due to the rough approximations involved in the evaluation of the numbers ∊μ for the latter species. The coupling constants aH5,10 for III⊖. and III⊕. are very close to the corresponding values aH4,6 for the radical ions of 1,3,5-tri-t-butylpentalene (II), in accord with the prediction of the MO model. A similarity is also found between the proton hyperfine data for III⊖. and those for the radical anions of structurally related 1,4-diphenyl-1,3-butadiene (V). On the other hand, there are striking changes in the coupling constants of the analogous protons on passing from III⊖. to the radical anions of dibenzo [a,e] cyclooctene (VI) and [16] annulene (VII), as a consequence of raising the symmetry from C2h to D2h and D4h, respectively.

Notizen: The linear dichroic absorption spectrum of 1,3,6,8-trans-15, 16-hexamethyl-dihydropyrene has been measured in stretched polyethylene at 77K, and CNDO-CI calculations with inclusion of singly and doubly excited configurations have been carried out on a series of alkyl bridged [14] annulenes with pyrene- and anthracene-shaped perimeters. Transitions to e3g → e4u type 1B states are well described, and the results indicate that additional low-energy excited states originate from e3g→ e5g and e2u → e4u type configurations interacting strongly with doubly excited configurations of the e3g, e3g → e4u, e4u type. The second excited singlet state responsible for the weak transition observed between the 1L bands may be assigned to one of these additional states, but it is probably of complex nature, similar to the ‘phantom’ state in linear polyenes.

Notizen: The Structures of the Oxidation Products formed by Hologenation of Furfural in WaterThe oxidation products formed on halogenating furfural in water are cis/trans-2,5-dihydroxy-2-(dihydroxymethyl)-2,5-dihydrofuran (5) and cis/trans-2,6-dihydroxy-2 H-pyran-3 (6H)-one (6) as shown by 1H- and 13C-NMR.-spectroscopy. A new, simple high-yield preparation of 5- and 6- solutions is described, in which sodium bromate is used as the oxidizing agent.

Notizen: Crystal structure analyses of five crystalline enamines together with recently published structural data for two other enamines reveal varying degree of pyramidality at the enamine nitrogen atom. The pyramidality appears to be most pronounced in enamines from piperidine and morpholine, less so in enamines derived from prolinoid amines. A pyrolidine enamine obtained from a derivative of cyclohexane-1,4-dione seems to have a virtually planar enamine group. The implications of these findings for current stereochemical problems in enamine chemistry are discussed.

Notizen: On the Sterochemical Course of Electrophilic Substitution at CH Groups in α-Position to the N-Atom of Hindered AmidesIt is shown by 1H-NMR. analysis of the aminoalcohol derivatives 4b and 4c that the lithiation/hydroxyalkylation with acetone of 1-nitroso-and 1-(2,4,6-triiso-propylbenzoyl)-4-phenyl-piperidine leads to configurationally different products. The assigned cis and trans configuration of the substituents in 4b and 4c, respectively, is compatible with the electronic structures 2 and 1, respectively, which were previously proposed for the lithio-derivatives 3 involved in such transformations.

Notizen: Conditions and implications for the calculation of self-consistent single determinant wave functions for Koopmans' ions are discussed and a recipe for practical computations is given. The concept of Koopmans' ions has been extended to localized ions and a definition for their reorganization energies is proposed. Calculations on formaldehyde serve as a numerical illustration.

Notizen: Upon flash pyrolysis between 580 to 660°, 2,4,6-tris(chloromethyl)mesitylene (2) leads to products formed through the loss of one, two and three molecules of HCl. The highly reactive chlorine free product is shown to be [6]radialene (1) both by its chemical reactions and by its spectral properties.

Notizen: Structure and Reactivity of a Triazolo-benzodiazepine/Oxalyl Chloride AdductReaction of oxalyl chloride with N, N-dimethyl-{8-chloro-6-(0-fluorophenyl)- 4H, 11 H-[1,2,4]triazolo [1,5-α] [1,4]benzodiazepine}-2-carboxamide (6a), the syn-thesis of which is described, leads to the cyclic adduct N, N-dimethyl-{2,12,12-trichloro-13a-(0-fluorophenyl)-11-oxo-10,11,12,13a-tetrahydro-5H, 9H-[1,3]oxazolo [3,2-d] [1,2,4]triazolo [1,5-a] [1,4]benzodiazepine}-7-carboxamide (7a). Upon thermolysis 7a is partly reconverted to the starting diazepine 6a via loss of the elements of oxalyl chloride. Reduction of 7a with sodium borohydride also yields 6ain addition to its dihydro derivative 9. Energetic treatment of 7a with sodium methoxide leads to the unexpected methoxydiazepines 10a and 10b, and mild treatment of 7a with sodium methoxide to the stereoselective formation of the two precursors of 10, namely the chloromethoxy derivative 11 and the dimethoxy derivative 12. Epimerization of 11 followed by nucleophilic substitution gives a mixture of two dimethoxy compounds, 12 and its epimer 14. The configurational assignments of these derivatives are based upon X-ray analysis of 12. A possible pathway for this unexpected substitution reaction is proposed.

Notizen: Leaf-gland pigments from labiatae: structures of 16 diterpenoids (coleons and royleanones) from Coleus coerulescens GÜRKEThe Abyssinian labiate Coleus coerulescens has been investigated for its leaf-gland pigments. From the very complex mixture of abietanoic diterpenoids the following pure constituents were isolated and their structures established: (1)Diosphenols: coleon C (1a), 16-O-acetyl-coleon C (1b), coleon W (1f);(2)A/B-trans-6, 7-diketones: coleon D (2b), 16-O-acetyl-coleon D (2c), coleon V (2a);(3)Spiro-coleons: 7,12-bis(O-desacetyl)-coleon N(3a), 12-O-desacetyl-coleon N (3b), coleon O (4), 6,12-bis (O-desacetyl)-coleon R (5a), 12-O-desacetyl-coleon R (5b), 3-O-desacetyl-3-O-formyl-coleon Y (5g);(4)Royleanones: The abeo-compounds 6a, 6b, and 7.Main compounds are 3b, 5e and 5g. This is the first record of a co-occurrence of diosphenols, 6,7-dioxo-coleons, spiro-coleons and royleanones. Preliminary experiments show that solvolytic opening of the cyclopropane-ring followed by tautomerisation, oxidation to hydroxy-p-benzoquinones or elimination to quinomethanes and subsequent nucleophilic attack of the solvent leads to compounds with a 2′-substituted propyl group at C(13), thus supporting the biosynthesis of the unusual coleon E side chain.

Notizen: Syntheses of the four stereoisomeric dihydropalustramic acids ([6-(1-hydroxypropyl)-2-piperidyl]acetic acids)(-)-Dihydropalustramic acid, a key product in the structure elucidation of the alkaloid palustrin, has been assigned the threo-cis structure 20 by comparison with the four stereoisomeric (±)-dihydropalustramic acids (threo-cis, threo-trans, erythro-cis, erythro-trans). The latter were synthesized by a new route to α, α′-di-substituted piperidines of this type. Ring closure to the piperidine ring with simultaneous stereospecific formation of the hydroxylated side chain has been achieved by reaction of the stereoisomeric methylesters of 7,8-epoxy-2-decenoic acids with benzylamine. Assignment of the configuration at the piperidine ring is based on careful comparison of the H-NMR. spectra of the N-benzylpiperidines and with the help of lanthanide shift reagents.

Notizen: 1H-and13C-NMR. spectra of methyl esters of the diastereomeric (±)-dihydropalustramic acids; structural correlation of (-)-dihydropalustramic acid with the alkaloid palustrinUnambiguous assignment of cis-trans configuration at the piperidine ring of the four diastereomeric methyl esters of the (±)-dihydropalustramic acids is based on the interpretation of 1H- and 13C-NMR. data. (-)-Dihydropalustramic acid, the important degradation product of the alkaloid palustrin is shown to be threo-cis-[6-(1-hydroxypropyl)-2-piperidyl]acetic acid. The same conclusion holds for palustrin and dihydropalustrin. Therefore, palustrin is threo-cis-17-(1-hydroxy-propyl)-1,5,10-triazabicyclo[11.4.0]heptadec-15-en-11-one.

Notizen: Determination of the absolute configuration of alkaloids from Equisetum sp.,e.g. (+)-palustrin, palustridin ((+)-hydrochloride), and (-)-dihydropalustramic acid and derivativesThe absolute configuration of the title alkaloids has been determined using chiroptical methods (ORD., superposition of CD. values of appropriate models and a modified Horeau method). (+)-Palustrin is (13R, 17 S, 1′S)-17-(1-hydroxypropyl)-1,5,10-triazabicyclo [11.4.0]heptadec-15-en-11-on.

Notizen: Synthesis of threo-cis/threo-trans- and erythro-cis/erythro-trans-dihydropalustrinThe first synthesis of a threefold protected spermidine, namely 3-benzyloxycarbonyl-N1-phthaloyl-N2-tosylspermidin (9) is presented. Each of the protecting groups can be removed selectively. After hydrazinolysis the resulting N3-benzyloxy-carbonyl-N2-tosylspermidine (10) has been condensed with methyl (2 E)-cis-7,8-epoxy-2-decenoate to the threo-cis/trans piperidines 17, and with methyl (2 E)-trans-7,8-epoxy-2-decenoate to the erythro-cis/trans piperidines 17, respectively. After catalytic removal of the Z group, the resulting aminoesters 13 and 18, in a melt with imidazole, underwent ring closure to the 13-membered lactames 14 and 19, respectively. reductive deprotection of the N-tosyl group with sodium/ammonia led to the stereoisomeric palustrines 15 and 20, respectively.

Notizen: Degradation of palustrin to (-)-dihydropalustramic acid ((2R,6S,1′S)-[6-(1′-hydroxypropyl)-2-piperidyl]acetic acid), and the structure of palustrin and palustridinThe structure of the macrocyclic alkaloid palustrin is shown to be 1a. Its piperidine unit can be obtained as (-)-dihydropalustramic acid (6a) by the following sequence of degradation reactions (Scheme 1): catalytic hydrogenation of 1a followed by methylation and Hofmann degradation provides the allyl base 4. the regioselectivity of the Hofmann elimination is explained by intramolecular proton abstraction at C(3) by C(18)-O-. Catalytic reduction of 4 and subsequent acidic hydrolysis yielded 6a and N, N-dimethylputrescine (=N,N-dimethyl-1,4-butanediamine; 7). Loss of the N-alkyl group in the formation of 6a occurs during the catalytic hydrogenation step. This interpretation is supported by the results of model experiments. The position of the double bond in 1a is deduced from the IR. spectrum of the bromo-δ-lactone 19 prepared by treatment of 1a with N-bromosuccinimide at pH 4 (Scheme 3). Some of our previously published results on the degradation of dihydropalustrin (2a) are obviously at variance with the newly proposed structure for palustrin (1a). They can easily be explained by assuming a partial hydrogenolysis of the C(17)-N(1) bond during the preparation of dihydropalustrin from palustrin. Periodate cleavage of dihydropalustramic acid methyl ester (6b) liberates propionaldehyde, which can be trapped by working at pH 7.5 (Scheme 2); at lower pH values it condenses rapidly with the simultaneously generated 3,4,5,6-tetrahydropyridine derivative 15. The structure of the condensation product is proposed to be 16 on the basis of the isolation of its hydrogenation product, an isomeric dihydropalustramic acid (17).