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.     

Déconjugaison d'énones dérivées de sucres Communication préliminaire

Deconjugation of sugars enones. Preliminary Communication Branched-chain sugar enones 1 and 2 ( R = Ac) deconjugated toposelectively (only the E isomers reacting) to 3 . The same phenomenon was noted in the case of Z- 4 which gave E- 5 . The kinetic parameters of these reactions favored a concerted mechanism, i.e. a [1, 5]-sigmatropic shift.     

Dérivés C-glycosyliques XXIII. Radicaux libres stables dérivés de sucre Communication préliminaire

Treated with 2,3-dimethyl-2,3-bis-(hydroxylamino)-butane, aldehydo-dialdofuranoses ( 1 ) gave a mixture of two compounds: a 1,3-dihydroxyimidazolidine ( 2 ) and a 1-hydroxyimidazoline ( 3 ). Oxidation (PbO₂) of compounds 3 gave stable free radicals having the structure of 2-C-Glycosyl-4,4,5,5-tetramethylimidazolines 1-oxyl ( 4 ), whereas 2-C-Glycosyl-4,4,5,5-tetramethylimidazolines 3-oxide 1-oxyl ( 5 ) were formed by oxidation of 2 . The ESR. spectra of compounds 4 and 5 establish the structure of the imidazoline part of these radicals and provide informations on the sugar moiety.     

Radicaux libres dérivés de sucres. V. Dérivés d'osamines N-hydroxylées et composés voisins Communication préliminaire

Free sugar radicals. V. Deoxyhydroxylaminosugar derivatives and related compounds We describe several synthetic routes to deoxyhydroxylaminosugar derivatives of the type Glyc-N(OH)-R where Glyc stands for a sugar moiety linked by any of its C-atoms except the anomeric one and R for one of the following substituants: H-atom, acyl, phosphoryl groups, aminoacid or sugar residues. Compounds of the above structure are potentially close analogs, homoisosteres, ? NOH? replacing ? O? , of biochemically important molecules. Under aerobic conditions, solutions of these derivatives contain minute concentrations of the corresponding nitroxide radicals which do not decrease significantly the resolution of the NMR. spectra but render these compounds usable as a new kind of spin labels. Spectroscopic properties (¹H-NMR., ¹³C-NMR., ESR.) of some of these compounds are reported.     

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.     

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.     

Dérivés de désoxy-hydroxylamino-sucres et radicaux libres diglycosylnitroxydes correspondants. Communication préliminaire

Deoxy-hydroxylamino-sugar Derivatives and Corresponding Diglycosylnitroxides Radicals A number of sugar aldonitrones, including C,N-diglycosylnitrones, and ketonitrones have been treated with Grignard reagents or cyanide anion leading to the corresponding deoxy-hydroxylamino-sugars. On oxidation (air, H₅IO₆ or PbO₂), these compounds gave the corresponding nitroxide radicals whose ESR. spectra are reported. Analogues of disaccharides, in which the interglycosidic O-bridge is replaced by a hydroxyimino group, have been obtained by reacting a partially blocked sugar bearing a free hemiacetal group either with a deoxy-hydroxylaminosugar or with hydroxylamine, followed by reaction with an aldehydosugar and a reducing agent (NaBH₄). These reactions represents the key synthetic steps for the oligosaccharide-type synthesis of deoxy-hydroxyimino-oligosaccharides. Their oxidation yielded the corresponding nitroxide radicals whose ESR. spectra gave information on the conformation about the ‘interglycosidic’ bridge. This type of compounds should constitute useful spin markers for biological studies.     

Synthèse et réactivité des bromhydrines dérivées de la chromone

Bromohydroxylated derivatives of chromone are obtained by addition of N-bromosuccinimide in dimethylsulfoxide. The configuration and conformation of these compounds are confirmed by NMR spectroscopy. Alkaline alcoholates react with these bromohydrins to give a ring contraction into 2-formyl-3-benzofuranone.     

Dérivés diglycosyliques. Communication préliminaire

Diglycosyl Derivatives. Preliminary communication Novel types of diglycosyl compounds, some of them bearing a resemblance to natural di- or tri-saccharides are described: a diglycosyldiyne ( 1 ), a diglycosylthiophene ( 2 ), a diglycosylaziridine ( 3 ), a diglycosyldioxolane ( 4 ), as well as six C,N-diglycosylnitrones, 9b–9f and 14 . These C,N-diglycosylnitrones, on treatment with an acetylenic Grignard reagent, led to the expected acetylenic diglycosyl-hydroxylamine 11 , whereas diglycosylisoxazolines (f. ex. 10 ) were obtained when these nitrones underwent 1,3-dipolar cycloaddition to acetylenic compounds.     

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 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.     

C-Glycosides V: Données mécanistiques sur l'halogénation d'hydrazones et d'oximes dérivées de sucres. Communication préliminaire

The bromination of aldehydo-sugars p-nitrophenylhydrazones has been studied and the gem-bromo-azo intermediates isolated and characterized in some cases. In the same way, in the chlorination of aldehydo-sugars oximes gem-chloro-nitroso intermediates have been obtained and in some instances isolated. These observations support a S_E2′ mechanism for such reactions.     

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.     

Dérivés de sucres benzimidazoliques et benzothiazoliques

Benzimidazole and benzothiazole sugar derivatives Simple aldehydosugars such as 1 or 2 , by reaction with o-phenylenediamine, gave the corresponding benzimidazoles 3 and 4 . Whereas the unperturbed α, β-unsaturated aldehydosugar D gave the benzodiazepine E upon treatment with o-phenylenediamine, the formyl-bearing alkenyl acetals 5 and 8 led, in the same conditions, to the benzimidazoles 6 and 9 respectively or, on reaction with o-aminothiophenol, to the benzothiazoles 7 and 10 respectively. This difference in reactivity is explained by the electrondonor ability of the oxygen atom of the alkenyl acetal function as shown by the ¹³C-RMN. spectra.     

Dérivés de l'hydroxyméthyl-5 furfural. I. Synthése de dérivés du di- et terfuranne

Addition of α, β-unsaturated sulfones or ketones to 5-hydroxmethyl-furaldehyde or related furanaldehydes in the presence of a thiazolium salt gives di or tetraketonic furan compounds. Dehydrative cyclizationled to di- and terfuryl derivatives.     

Triazènes et benzotriazines dérivés de sucres

Sugar triazenes and benzotriazines Several triazenylsugars have been prepared, generally in good yields, by treating an amino sugar with a substituted benzenediazonium salt. The triazenylsugars bearing a hydrogen atom on the triazenyl group are acetylated on the nitrogen atom closest to the glycosyl moiety (N(1)), even when the proton exchanged sites between N(1) and N(3). When an acetyl or a methoxycarbonyl group was present in the ortho position of the benzene ring cyclization took place leading to a 3,4-dihydro-4-methylidene-1,2,3-benzo[d]triazine or a 3,4-dihydro-1,2,3-benzo[d]triazin-4-one respectively.     

Dérivés d'énose- et d'ynosephosphonates et composés voisins. Communication préliminaire

Derivatives of enose- and ynosephosphonates and related compounds. Preliminary communication The gem-dibromo terminal enoses 1 and 7 are convenient sources of glycosylacetylenes which upon reaction with phosphorus electrophiles gave the phosphorusbearing acetylenic sugars 4, 5 and 8 . Compounds 5 and 8 underwent cycloaddition reactions leading to isoxazolyl-C-glycosides 6 and 9 respectively. The nitroolefinic sugar derivative 11 gave upon bromination-dehydrobromination the first example of a new kind of potentially useful synthetic intermediates, the gem-bromonitroenose 12 . The enosephosphonate 13 was also prepared from 11 . The diglycosylhydroxylamine 18 represents another type of phosphorus-bearing acetylenic sugar derivative. Some ¹H- and ¹³C-NMR. data relative to the new types of phosphorus-containing sugar derivatives synthesized are given.     

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.