Recherches dans la série des cyclitols XLVI. Actions de diazoalcanes sur la pentahydroxy-2,4,6/3,5-cyclohexanone et sur son dérivé penta-O-acétylé II. Etude de pentahydroxy-alkyl-C-cycloheptanones

On treatment with higher diazoalkanes, 2,4,6/3,5-penta-acetoxy-cyclohexanone (penta-O-acetyl-myo-inosose-2 or -scyllo-inosose) afforded by ring expansion all-trans-penta-acetoxy-C-alkyl-cycloheptanones, which by deacylation were converted to hemiacetals. The reactions with diazoalkanes of the penta-acetoxy-inosose in the presence of aluminium chloride and of the free inosose in water solution have also been studied. The structure, the configuration, and, in some cases, the conformation of the new compounds have been established and some of their reactions have been investigated. The mechanisms of formation of the ring expansion products and of the concomitant spiro-epoxides have been discussed.     

Recherches dans la série des cyclitols XXXVIII Etudes conformationnelles de dérivés cyclopenténiques disubstitués-3, 5

Cyclopentenones substituted in position 4, and 3, 5-cis or -trans disubstituted cyclopentenes have been studied by NMR. and by IR. spectroscopy. Cyclopentenone derivatives and cyclopentene derivatives adopt a quasi-coplanar and an envelope conformation, respectively. The preferential orientation of the substituents has been established according to their nature and to the solvents by correlation to the vicinal and the long-range coupling constants.     

Interactions intramoléculaires. XXVI—Constantes de couplage et hétérogénéités conformationnelles dans une série de R-3 et R-5 cyano-4 cyclohexènes deutériés (R=méthyl ou t-butyl)

For trans-3-R- and 5-R-1-acetoxy-4-cyanocyclohexene-6,6-d₂ the molar fractions of diequatorial conformers are 0.83 (3-methyl), 0.68 (5-methyl), 0.57 (3-tert-butyl) and 0.55–0.69 (5-tert-butyl). For the last two compounds the values of the coupling constants are in agreement with the hypothesis of an ee?aa equilibrium. For the cis isomers, the molar fractions of equatorial alkyl conformers are 0.76 (3-methyl and 5-methyl) and 1.0 (3-tert-butyl and 5-tert-butyl). The cis-1-acetoxy-3-tert-butyl-4-methoxycarbonyl-cyclohexene presents a conformational heterogeneity. The conformational free energy of the methyl group in position 4 has been evaluated as ?0.6 kcal mol^?1 (2.5 kJ mol^?1).     

Analyse conformationnelle de cétones cyclopropaniques par RMN à l'aide des déplacements paramagnétiques induits par Eu(dpm)3

The lanthanide induced shifts (LIS) of the lanthanide shift reagent Eu(dpm)₃ are reported for several cyclopropyl ketones. The conformational preference of the cyclopropanoyl group is determined via LIS by comparison with two compounds: dispiro-[2.1.2.2]nonane-4-one and 4,4,5-trimethyl bicyclo[3.1.0]hexane 2-one which are respectively in s-cis and s-trans conformation.     

Utilisation d'ylides du phosphore non stabilisés en chimie des sucres VI. Sucres ramifiés dérivés des di-O-isopropylidène-1,2:5,6-α-D-ribo-et-α-D-xylo-hexofurannosul-3-oses

The cis and trans isomers of 3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-methylthiomethylene-α-D -xylo- and -α-D -ribo-hexofuranoses have been prepared by treatment of 1,2:5,6-di-O-isopropylidene-α-D -xylo- and -α-D -ribo-hexofuran-3-uloses with methylthiomethylene-triphenylphosphorane. Configurations are assigned by NMR. A new type of ⁴J is described. Hydrogenation-desulfurization of the methylthiovinylic sugars affords 3-deoxy-3-methyl sugars of the D -allo, D -gulo, and D -galacto series. Derivatives of 3-deoxy-3-methyl-D -lyxose and 3-deoxy-3-methyl-D -ribose are prepared by chain-shortening of derivatives of the corresponding 3-deoxy-3-methyl-hexoses.     

The stereochemistry of the dichlorocobalt(III) complexes with (2S,5S,9S)- and (2S,5R,9S)-trimethyltriethylenetetraamines

Dichlorocobalt(III) complexes of (2S,5S,9S)-trimethyltriethylenetetraamine (L₁) and (2S,5R,9S)-trimethyltriethylenetetraamine (L₂) have been prepared. Both L₁ and L₂ coordinate to the cobalt(III) ion to give three isomers: Λ-cis-α, Δ-cis-β, trans isomers for L₁ and Δ-cis-α, Δ-cis-β, trans isomers for L₂. Each of the trans-dichloro complexes of the two ligands have been isomerized stereospecifically to the cis-α-dichloro complex in methanol, and each of the cis-α-dichloro complexes stereospecifically to the trans-diaqua complex in water. Both the geometrical and optical inversions took place at the same time in the observed stereospecific isomerizations.     

Tordanone,un stéroïde replié avec une jonction de cycle A/B β-cis (5β) et B/C α-cis(8α)

Tordanone, a Twice Bent Steroid Structure with Ring A/B β-cis(5β)- and Ring B/C α-cis(8α)-Fused The 3β, 14α, 25-trihydroxy-5β, 8α-cholestan-6-one ( = tordanone; 4 ) has been prepared by stereospecific hydrogenation of 3β, 14α, 25-trihydroxy-5β-cholesta-7,22ξ-dien-6-one ( 5 ). This is the first stereospecific synthesis of a B/C cis-fused steroid belonging to the 5β, 8α -cholestane group with a H-atom at positions 5β (A/B cis-fused) and 8α. The resulting twice bent structure shows a particularly strong steric hindrance of the β-face where CH₃(18) at the C/D ring junction and H_β? C(7) of the B ring are very close to each other. Structural features and mechanistic aspects of the hydrogenation are discussed.     

Structures cristallines et moléculaires des muses macrocycliques. II. La trans-civettone et sa 2,4-dinitrophénylhydrazone

Crystal and Molecular Structure of Macrocyclic MUSKS. II. trans-Civetone and its 2, 4-Dinitrophenylhydrazone The trans and cis isomers of civetone (C₁₇H₃₀O) crystallize in isomorphous systems and form plastic crystals (tetragonal, space group I4₁ a=9.95 (4), c = 32.79 (1) Å, Z = 8). Mixed crystals were prepared with cis-civetone as second component. Accordingly the diffuse structural model obtained for the disordered phase of the cis-isomer [1] is also regarded as representative of that of trans-civetone. The crystal structure of trans-civetone 2,4-dinitrophenylhydrazone (DNPHTC; C₂₃H₃₄N₄, Monoclinic, Space group P2₁/c, a=8.364(2), b=7.971(1), c=36.025(8) Å, β=91.44 (2)°) was solved by direct methods and refined to a final R of 0.09 (R_w = 0.021). The macrocycle adopts a sexangular conformation [23*434*44*], and its mean plane is approximatively perpendicular to that of the aromatic substituent. Empirical force field calculations have shown that the DNPH substituent has very little influence on the macrocycle conformation. The intermolecular interactions take place essentially between groups of the same type: macrocycle…macrocycle and DNPH…DNPH.     

ISOMER COMPOSITION and SPECTRA OF THE DARK and LIGHT ADAPTED FORMS OF ARTIFICIAL BACTERIORHODOPSINS*

Abstract– The isomer composition and spectral properties of 15 artificial bacteriorhodopsin (bR) pigments, based on a series of retinal analogs with polyene residue modified below C₉ are determined for both dark-adapted (DA) and light-adapted (LA) forms. Similarly to native bR, in all cases only two isomers, C₁₃=C₁₄cis (13-cis) and M-trans, are observed. However, the artificial DA pigments have a lower 13-d.s content than native DA bR (? 66%) while the corresponding LA pigments have a much higher 13-cis content (11-69%) than native LA bR (<2%). Thus, in variance with the native pigment, in all of the artificial systems light also induced the reversed all-trans13-cis process. The data are accounted for in terms of specific steric interactions between the polyene and the protein binding site which allow a (C₁₅-anti)(C_ls-syn) isomerization during the photocycle of the artificial pigments, but not in the case of native bR. This accounts for the high proton pumping efficiency of the natural pigment. The nature of a highly red shifted light-adapted form of two of the artificial pigments is investigated and discussed. It is also shown that, in variance with native bR, several artificial pigments exhibit identical absorption spectra for their 13-cis and all-trans isomers. It is concluded that the spectral data for the above species of artificial pigments do not lead to a clear molecular model for the origin of the spectral shift between 13-cis and all-trans bR.     

Mécanisme de solvolyse des cis - et trans-(p-toluénesulfonates) d'aryl1-2-cyclopentyle II. Etude des étapes ultérieures à l'ionisation lors de la solvolyse des cis-(p-toluénesulfonates) d'aryl-2-cyclopentyle

Solvolysis Mechanism of cis- and trans-2-Arylylopentylp- Toluenesulfonates, Subsequent Step in cis-2-Arylcyclopentyl p-Toluenesulfonate Solvolysis The solvolysis of a series of 1-deuteriated, 2-deuteriated, and undeuteriated cis-2-arylcyclopentyl p-toluenesulfonates in HCOOH, AcOH, and EtOH has been studied. We have shown that classical secondary carbocation arising from substrate ionisation undergoes two concurrent processes, namely k_c (direct products formation) and k_ip (hydrogenium bridged ion formation as tertiary carbocation or products precursor). The intrinsic properties of solvent and the aryl substitutant electronic effects the total solvolysis rate and the respective contributions of k _c and k _ip processes. Comparing the observed and calculated kinetic isotope of D–C(2) allows one to conclude that no step can called ‘rate-determining step’ but that the steps following ionisation have a preponderent effect on the total solovolysis rate.     

Recherches dans la série des cyclitols XXXVII Etude par spectrométrie de masse

Low resolution mass spectra of cyclohexane-triols, -tetrols, -pentols and -hexols and of some of their deuterium labelled derivatives have been measured. The results indicate that for some geometrical isomers quantitative differences between ion intensities are significant, allowing to deduce the stereochemistry of the molecule from its mass spectrum. In all these compounds the electron impact induced elimination of water occurs mainly by interaction between OH groups. There is a correlation between the relative abundance of (M – H₂O)⁺ and (M ?2 H₂O)⁺ ions and the number of axial hydroxyls in the more stable conformation of the molecule. Difficulties encountered in deducing fragmentation patterns, and determination of number and position of deuterium atoms in the molecule of ms-inositol are discussed.     

Synthèse et désamination enzymatique des C-hydroxyméthyl-3′- et C-méthyl-3′-β-D-xylofurannosyl-9-adénines

Synthesis and enzymatic deamination of 3′-C-hydroxymethyl- and 3′-C-methyl-β-D -xylofuranosyl-9-adenines The title compounds have been prepared by classical synthetic steps after having optimized the nature of the blocking groups. Both nucleosides were found to be substrates of adenosine aminohydrolase which proved that C(3′)-branched-chain sugar nucleosides can be deaminated when the branched-chain is exo (trans relative to the base) if a suitably disposed hydroxy group is available on the endo side of the furanose ring.     

Réactions d'élimination présentées par des acides polyhydroxyadipiques

The tetrahydroxyadipic acids and one trihydroxyadipic acid have been methylated, using methyl iodide and silver oxide in the presence of dimethylformamide. In addition to Δ²-di- or tri-methoxyadipic esters and the products expected for a double E2 elimination, cis-trans α, α'-dimethoxymuconic ester was frequently the principal product. The proposed theoretical interpretations involve as intermediates either a silver complex or a lactonic compound. A few preferential conformations, based on NMR. data, are proposed.     

Structures cristallines et moléculaires des muscs macrocycliques. I. La cis-civettone et les variétés polymorphes α et β de sa 2,4-dinitrophénylhydrazone

Crystal and Molecular Structure of Macrocyclic Musks. I. cis-Civetone and polymorphous α- and β-forms of his 2,4-dinitrophenylhydrazone cis-Civetone (C₁₇H₃₀O) forms tetragonal plastic crystals, space groupe 14¹; a = 9.95(4), c = 32.79(1) Å; Z = 8. The plastic phase exists in a wide temperature range and 731 reflexions could be collected at 153 K. The highly disordered structure model was obtained by the use of direct methods. The molecules appear as ring-shaped diffuse electron-density distributions located in special position. Two polymorphous crystalline forms were isolated for the 2,4-dinitrophenyl-hydrazone of cis-civetone (DNPHCC). Both forms are triclinic, space group P1 . Z = 2 (α-Form: a = 6.279(5), b = 12.605(8), c = 15.253(10) Å, α = 105.49(7). β = 100.31 (6), γ = 91.23(7)°; β-Form: a = 7.950(2). b = 8.405 (2). c = 18.233(4) Å, α = 100.28(2), β = 92.29(3), γ = 94.18(2)°). The structures were solved by direct methods and refined to R = 0.11. Each polymorph is associated with a different quinquangular conformation of the macrocycle. In the crystals the intermolecular interactions between macrocycles and aromatic substituents are minimized, the DNPH group being oriented in a face-to-face arrangement across a centre of symmetry. Empirical force field calculations show that the overall intluence of the DNPH moiety on the attached cycle does not significantly modify its conformation with regard to that of the ketone itself.     

Interactions intramoléculaires. XXVII—Etudes structurales en série bicyclo[4.1.0]heptanique (effets d'anisotropie sur les déplacements chimiques du proton; constantes de couplage et équilibres conformationnels)

All the ¹H n.m.r. parameters of the following derivatives of 1,6-dimethylbicyclo[4.1.0]heptane are determined: 3,4-dimethoxycarbonyl (3 diastereoisomers), cis- and trans-3-methoxycarbonyl-2,2,5,5-d₄, cis- and trans-3-methyl-3-methoxycarbonyl; the cis- and trans-1,5,5-trimethylbicyclo[4.1.0]-3-heptanols are studied in the same way. The different chemical shifts are correlated with the aid of a collection of empiral increments. The conformational equilibria are determined from the vicinal coupling constants; the conformational free energies of the COOCH₃ group are evaluated; the part played by gauche interactions is considered.     

Interactions intramoleculaires. XXI—Constantes de couplage et interactions gauches avec un groupement t-butyle (molécules cyclohexaniques deutériées)

Different isotopic modifications of deuterated products of 1-t-butlyl-4-methoxycarbonyl cyclohexene (d₄-3,3,6,6), cis- and trans-3-methyl-4-cyanocyclohexene (d₃-3,6,6), cis- and trans-3-methyl-4-cyanocyclohexene (d₃,6,6), cis- and trans-3-t-butyl-4-methoxycarbonylcyclohexene (d₃,-3,6,6) are shown by nuclear magnetic resonance spectral analysis. By comparison of ³J and ⁴J coupling constants of model molecules and molecules with large gauche interactions, we obtain proof that the latter are in a chair conformation with moderate cycle deformations.     

Utilisation d'ylides du phosphore en chimie des sucres VII. Synthèse de sucres ramifiés des types «streptose» et «apiose». Communication préliminaire

A new high-yielding route to branched-chain sugars of the streptose or the apiose type having at the branching point a configuration epimeric with that which would be obtained by the classical synthesis using Grignard reagents is described. The main steps are the preparation of branched-chain unsaturated cyano sugars by reaction of cyanomethylene triphenylphosphorane with keto sugars and the cis-dihydroxylation (KMnO₄) of the so obtained cyano sugars. The cis and the trans isomers of a series of cyanovinylidenic sugars have been separated and the stereodependence of the long-range coupling constants in this class of compounds has been examined.     

Synthèse de spiro-pyrazolines par cycloaddition du diazométhane sur des sucres insaturés ramifiés. Influence de l'isomérie géométrique sur l'orientation de la réaction Communication préliminaire

The orientation of the cycloaddition of diazomethane on unsaturated branchedchain sugars has been studied. For 3-C-cyanomethylidene-3-deoxy-1,2-O-isopropylidene-α-D-glycero-tetrofuranose the orientation was ‘normal’ and did not depend on the configuration at the double bond. The same situation prevailed with derivatives of 3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-methylidene-α-D-xylo-hexofuranose. For the 3-C-acylmethylidene- and the 3-C-cyanomethylidene-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofuranoses, the trans-(H–C(3′)–C(2))-isomer gave the ‘normal’ cycloadduct whereas the cis-isomer gave predominantly the αabnormal spiro-pyrazoline. This observation represents the first instance where the regioselectivity of a cycloaddition reaction is affected by the geometrical isomerism of the dipolarophile. The most probable explanation of the phenomenon is the conformational perturbation about the C(4)--C(5) bond of the unsaturated sugars induced by a change in the configuration at C(3). The consequence of that ‘conformational transmission’ of a difference in configuration at C(3) is that the steric crowding on the cis- than in the trans-isomer. Several novel examples of a new series of C-glycosylidenic derivatives, the spiro-pyrazolines, are described.     

Contribution à la connaissance des o-menthols et des o-menthones (carquéjanols et carquéjanones) - 1ère communication

The mixture of carquejanols obtained from carquejol of carqueja oil has been converted in ketones. The alkohols obtained respectively by hydrogenation on Pt(O₂), by lithium-aluminiumhydride reduction and by Meerwein-Ponndorf-Verley reaction have been separated by vapour phase chromatography. The ketones obtained from the Beckmann oxidation of the alkohols has been identified as carquejanone and isocarquejanone by application of the Auwers-Skita rule.     

Utilisation d'ylides du phosphore en chimie des sucres,X. Synthèse stéréospécifique de l'épimère en C3 du streptose et d'autres sucres ramifiés,dérivés de désoxy-5-pentoses, à groupements gem-hydroxy-formyle ou gem-hydroxy-hydroxyméthyle

The synthesis of branched-chain sugars of the gem-hydroxy-formyl and the gem-hydroxy-hydroxymethyl types is described. A 5-deoxy-1,2-O-isopropylidene-furanos-3-ulose is treated with cyanomethylene-triphenyl-phosphorane, yielding the two geometrical isomers of the corresponding branched-chain unsaturated sugar. Cis-dihydroxylation(KMnO₄) of these cyanomethylenic compounds affords stereoselectively and in high yield the gem-hydroxy-formyl branched chain sugars whose formyl group is on the more hindered face of the furanose ring. The hydroxymethyl analogues of the latter compounds are readily prepared by their borohydride reduction. This method constitutes a new general route to type A branched-chain sugars epimeric at the branching-point with the sugars which would have been obtained by the classical procedure involving Grignard reagents.