Synthèse de sucres aminès ramifiés II. Synthèse et réactions de spiro-aziridines. Communication préliminaire

Treatment of 3-C-cyano-1,2:5,6-di-O-isopropylidene-3-O-(toluene-p-sulfonyl)-α-D -allofurannose with AlLiH₄ or RMgX yields spiro-aziridines with two identical substituents on C(3′) (? H, ? CH₃, ? C₂H₅). Reactions of these products and their derivatives are briefly described. If the C(3′) substituents are protons, the aziridine ring is easily opened. In acidic media (HCl), an amino-sugar containing the branched chain ? CH₂Cl is produced; with hydrogenation, a ? CH₃ branched chain results. If the C(3′) substituents are methyl groups, the aziridine ring cannot be opened neither with HCl nor with hydrogen. The acetylated derivative of this latter compound rearranges to the corresponding allylamide with HCl. For both types of spiro-aziridine, the nitrous deamination leads to the corresponding alkene.     

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.     

Préparation de phosphonates de sucres ramifiés par addition nucléophile conjuguée. Communication préliminaire

Preparation of unsaturated sugars phosphonates using nucleophilic conjugate addition Different types of phosphorus nucleophiles underwent conjugate addition reaction with one of the branched-chain sugars 4, 5 or 11 the addition taking place either on the endo or the exo face of the furanose ring (or on both faces in the case of 11 ). The configuration at C(3) of these new phosphorus-bearing types of sugars as well as the configuration at the phosphorus atom of the cyclic phosphinates 9 and 10 was established by NMR. (³J_P,H–C(2), ³J_P,C(1)). Small amounts (7%) of the spiro enol phosphonate 16 were formed when 11 reacted with trimethyl phosphite.     

Ylides du soufre dérivés de sucres Communication préliminaire

S-Methylation of 6-S-benzyl-6-deoxy-1,2-O-isopropylidene-3-O-methyl-α-D-xylo-6-thiohexofuranos-5-ulose ( 1 ) gave the expected sulfonium salt 2 which on alcaline treatment yielded the stable sulfur ylide 3 . This compound constitutes an useful synthetic intermediate in carbohydrate chemistry. On heating in 1,2-dimethoxyethane, it underwent a Stevens rearrangement which led to an extension of the carbon chain of the sugar and, reacted with Michael acceptors, it gave cyclopropanation reactions.     

Dérivés C-glycosyliques. VII. Synthèse et réactions de nitrones dérivées de sucres. Communication préliminaire

The syntheses of three types of sugar nitrones (aldonitrone, ketonitrone and α-β unsaturated aldonitrone) are described. On 1,3-dipolar cycloaddition with phenylacetylene, the aldonitrone gave two Δ₄-isoxazolines epimeric at the new asymetric carbon, while the same reaction on the ketonitrone led to a spiro-Δ₄-isoxazoline. The reaction of these nitrones with carbon nucleophiles like phenylethynylmagnesium bromide constitutes a novel chain-extension reaction in carbohydrate chemistry.     

Synthèse de sucres aminés ramifiés. IV Synthèse de quelques dérivés nouveaux par l'intermédiaire d'une hexose-spiro-aziridine

Treatment of 3-C-cyano-1,2:5,6-di-O-isopropylidene-3-O-(toluene-p-sulfonyl)-α-D -allofurannose with AlLiH₄ yields a sugar-spiro-aziridine and a branched chain sulfonamide. Reaction mechanisms are briefly discussed and the configurations of the products obtained are proved by chemical reactions. With hydrogenation, the spiro compound is opened to a branched chain amino sugar with the same tertiary carbon as in vancosamine. Several derivatives of this new compound are described: the 6-deoxy sugars in series L and D and the pentose resulting from its oxidation by periodic acid. The conformation around C(4)–C(5) bond is deduced for three compounds from NMR. data.     

Utilisation d'ylides du phosphore en chimie des sucres. XVIII Synthèse de furannoses à insaturation conjuguée. Communication préliminaire

Several sugars with conjugated unsaturation (dienes or α, β-unsaturated carbonyl compounds) have been synthesised by use of Wittig reactions. Keto-sugars bearing a carbonyl group α to a furanose ring are prone to undergo an elimination leading to conjugated unsaturated systems. This constitutes a novel kind of side-reaction in the application of Wittig reactions to carbonyl sugars. The synthesis of a new kind of acetylenic sugar is also described.     

Utilisation d'ylides du phosphore en chimie des sucres. XI. Synthèse des quatre didésoxy-3, 5-méthyl-3-pentoses parl'intermédiaire de sucres insaturés ramifiés

Treated with methylthiomethylenetriphenylphosphorane, 5-deoxy-1,2-O-iso-propylidene-β-D -threo- and -α-D -erythro-furanos-3-uloses led with good yields to a mixture of the cis-trans isomers of the corresponding methylthiovinylidenic sugars. There was no inversion of configuration at C(4) with the thero-furanosulose and a small one (7%) with its erythro isomer. These unsaturated branched-chain thio-sugars are useful synthetic intermediates. For examples, the desulfurization-hydrogenation (Raney Nickel) of each of these alkenes afforded in good yield two 3-deoxy-3-C-methyl-pentoses epimeric at C(3) and having the same configuration at C(4) as the starting alkenes. In all cases the isomer formed by attack from the less hindered face of the double bond was the preponderant one.     

Réarrangements d'acétonides de sucres carbonylés. Communication préliminaire

Isopropylidene derivatives of keto- or aldehydo-sugars are susceptible to rearrangements involving participation of the dioxolane ring.     

Un nouveau type de sucres azotés,les gem-azo-alcools. Communication préliminaire

Treatment of keto-sugar p-nitrophenylhydrazones with lead tetraacetate led to the corresponding gem-azo-acetates. The reaction is highly stereoselective, only one of the two possible epimers at the new asymmetric carbon being formed in measurable quantity. Catalytic de-acylation of these gem-azo-acetates yielded, quantitatively, representatives of a new class of nitrogen-containing sugars: the gem-azo-alcohols. When treated with potassium t-butylate, the gem-azoacetates underwent a rearrangement with ring expansion leading to N-aminolactams.     

Utilisation d'ylides du phosphore en chimie des sucres. XX. Synthèse de sucres acétyléniques et réarrangment d'intermédiaires carbénoïdes. Communication préliminaire

Two novel methods for the synthesis of terminal acetylenic sugars, both involving a chain extension by one carbon unit, are described. In the first procedure, an aldehydo-sugar is treated with dibromomethylenetriphenyl-phosphorane, then with n-butyllithium and finally with water. The second method involves an one-step reaction between an aldehydo-sugar and dimethyl diazomethylphosphonate. The acetylenic sugars obtained are valuable synthetic intermediates for the preparation of heterocyclic C-nucleosides by 1,3-dipolar cycloaddition reactions and some examples of syntheses of this type are described. Treatment of keto-sugars with dimethyl diazomethylphosphonate led to an intermediate carbenoid species which reacted by insertion into a C? H bond in one case and underwent nucleophilic attack by a methoxy group in a second case.     

Action de nucléophiles sur des sucres ramifiés cyanovinylidéniques: Addition conjuguée,stéréomutation,migration de doubles liaisons. Communication préliminaire

When treated with a series of nucleophiles cis-3-cyanomethylene-3-deocy-1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofurannose ( 1 ) may yield its trans isomer, a product of allylic isomerization or a product of conjugate addition, depending on the nature of the nucleophile. The configuration of the starting material is also important as shown by the differences in reactivity between 1 and its trans-xylo isomer 8 .     

Utilisation de techniques d'amination réductrice pour la synthèse d'amino-sucres de différents types. Communication préliminaire

Synthesis of amino-sugars using reductive amination reactions. Preliminary communication Treatment of aldehydo- or keto-sugars with primary or secondary amines and hydrogen in the presence of a catalyst (Pd/C) gave with good to excellent yields (67–96%) the expected secondary or tertiary amines. Primary amines can be obtained by using benzylamine, a hydrogenolysis taking place during the reaction.     

Esters phosphoriques,phosphonates et oxydes de phosphine dérivés de sucres. Communication préliminaire

Some sugar phosphates, phosphonates and phosphine oxides, Preliminary communication Some new phosphates of 1, 2-O-isopropylidene-α-D-ribofuranose have been prepared. Reactions of 3-C-cyanomethylidene-3-deoxy-1, 2-O-isopropylidene-5-O-trityl-α-D -erythro-pentofuranose (9) have been studied. On treatment with phosphorus nucleophiles, 9 led to phosphorus bearing branched-chain sugar derivatives. Branched-chain cyanosugars as 15 and 16 prepared by cis-vic-dihydroxylation of 9 constitute interesting potential precursors of new types of cyclic sugar phosphates.     

Dérivés C-Glycosyliques XXXII. Synthèse de dérivés spiro-C-glycosylidéniques par cyclisation nucléophile. Communication préliminaire

C -Glycosylic derivatives XXXII. Synthesis of spiro-C -glycosylidenic derivatives via nucleophilic cyclization. On treatment with compounds bearing two nucleophilic groups as ethylenediamine, o-phenylenediamine or their monooxa or monothia analogues, 1,2:5, 6-di-O-isopropylidene-α-D -ribo-hexofuranos-3-ulose gave with excellent yields the corresponding spiro-C-glycosylidenic derivative; for example, when using o-phenylenediamine, a spirobenzimidazoline ( 5 ) was obtained. The latter compound underwent, on oxidation, a ring expansion to a morpholinobenzimidazole ( 8 ). Spirobenzodiazepines, spirobenzooxazepines and spirobenzothiazepines were formed when applying the same type of cyclization reaction to 3-C-acetylmethylene-3-deoxy-1,2:5,6-di-O-isopropylidene-α-D -ribo- and α-D -xylo-hexofuranoses.     

Utilisation d'ylides du phosphore non stabilisés en chimie des sucres. IV. Nouveaux exemples de sucres méthylthiovinyliques terminaux. Communication préliminaire

The previously described one-carbon chain extension of aldehydo-sugars with methylthiomethylene-triphenylphosphorane has been successfully applied to an anhydro-aldehydo-sugar and two w-aldehydo-sugars. Some spectroscopic properties of the so obtained methylthiovinylic sugars are given.     

Synthèse électrochimique du cycle époxydique. Communication préliminaire

The polarographic behaviour of ditosyloxy alkanes TsO(CH₂)_nOTs in aprotic medium suggests that intramolecular cyclisation takes place after reductive cleavage of a single SO₂? O bond at the dropping electrode. This hypothesis was verified by controlled potential electrolysis of the lower homologues at a mercury cathode. High yields of epoxy compounds are obtained by this method.     

Synthèse de sucres aminés ramifiés III. Synthèse et réactions de 1′α-amino-nitrile dérivé du di-O-isopropylidène-1,2:5,6-α-D-ribo-hexofurannosul-3-ose

The addition of cyanohydric acid to 1,2:5,6-di-O-isopropylidene-α-D -ribo-hexofurannos-3-ulose can be sterically controlled. Under kinetic conditions, the allo cyanohydrine epimer is formed, under thermodynamic conditions, the gluco epimer is formed. The configuration of these two products is proved by their chemical reactions. Hydration followed by hydrolysis of the nitrile group of the allo epimer (O-acetyl derivative) gives the 3-C-carboxy-1,2-O-isopropyloidene compound. This product forms the corresponding γ or δ-lactone with hydroxyl ( 5 ) or ( 6 ). On the other hand, after hydrolysis of 5,6-isopropylidene, the 3-O-acetyl derivative of the gluco epimer gives an acetyl migration from position 3 to position 5 and finally to position 6. By reaction of the allo epimer with NH₃ and CN^?, an aminonitrile is formed. The allo configuration is deduced from the above mentioned reaction and from IR. and NMR. data. Several acetylated and trifluoracetylated derivatives of these products are described. The oxidation of the nitrile group to the amide group is possible with both epimeric cyanohydrines and the amino-nitrile.     

Radicaux libres dérivés de sucres. Partie. VII. Analogues de nucléosides marqués par un spin. Communication préliminaire

Sugar Free Radicals. VIII. Spin-Labeled Nucleosides Analogs A series of 5′-deoxy-5′-hydroxylamino derivatives of adenosine and uridine have been prepared by reduction of the corresponding oxime or nitrone. ‘Second generation’ 3′-deoxy-3′-N-aryl(or N-alkyl) hydroxylamino-β-D -xylofuranosyluracils have also been synthesized by a one-pot reaction including the following elementary steps: deblocking of the starting material, reduction of the 3′-deoxy-3′-oximinouridine, condensation of the resulting hydroxylamine with an aldehyde, reduction of the nitrone formed. The deoxy-hydroxylaminonucleosides oxidized spontaneously in the air (or in presence of traces of PbO₂) to give the corresponding nitroxide free radicals, ESR spectra of which furnished useful informations on their structures. Some of these modified nucleosides bore notable cytotoxic or antiviral activities.     

Nouveaux exemples de radicaux libres stables de dérivés hétérocycliques de sucres. Communication préliminaire

Some more examples of stable free radicals of carbohydrate heterocyclic derivatives 2-Glycosyl-4,4,5,5-tetramethylimidazoline- 3-oxide-1-oxyls and 2-glycosyl-4,4,5,5-tetramethylimidazoline 1-oxyls have been prepared in nine carbohydrate series, which proves the generality of the method. The hyperfine coupling constant between the free electron and the α-proton of the glycosyl group is never very large (0-2.3 G) but a correlation between its value and the structure of the aglycone has been noted. Free radicals of that type, stable in aqueous solutions, are potentially interesting for biological studies.