Nouveaux types de sucres acétyléniques. Communication préliminaire

Novel types of acetylenic sugars The coupling, following Cadiot's procedure, of a 6-bromo-5,6-dideoxy-1,2-O-isopropylidène-3-O-methyl-α-D -xylo-hex-5-yno-1, 4-furanose (1) with phenylacetylene, 2-propyn-1-ol or terminal acetylenic sugars gave with excellent yields the expected diynes (an enediyne when the terminal acetylene was the 3,5, 6-trideoxy-1,2-O-isopropylidene-α-D -glycero-hex-3-en-5-yno-1,4-furanose 7 ). The chloro analogue 8 of 1 on treatment with lithium thiophenate gave the corresponding phenylthio-acetylenic sugar 9 . An acetylene was also formed by reacting the gem-difluoro-olefinic sugar 10 with butyllithium whereas the same olefinic sugar and its 3-O-benzyl analogue 11 gave only a gem-fluoro-arylthio-olefinic sugar (13–15) as a mixture of the Z and E isomers (Z/E > 4) when treated with the conjugate base of an arylmercaptan.     

Préparation de dérivés de sucres acétyléniques terminaux et d'acides ynuroniques par réaction de Wittig. Note de laboratoire

Synthesis of Terminal Acetylenic Sugars Derivatives and Ynuronic Acids Derivatives by Use of a Wittig Reaction The method described for the preparation of terminal acetylenic sugars presents two advantages over earlier procedures: no new asymmetric center is created and the chain can be extended by one or more C-atoms. The method also allows preparation of ynuronic acids. The aldehydosugars derivatives 1–7 gave in good to excellent yields the corresponding gem-dibromoenoses 8–14 from which either the terminal acetylenic sugars derivatives 15–21 or the ynuronic acids 22–24 were easily prepared. A few examples of 1,3-dipolar cycloadditions (leading to 28–30 ) with these acetylenic sugar derivatives are also described.     

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 sucres à groupement gem-dihalogénoéthényle

Carbohydrate Derivatives Bearing a gem-Dihalogenoethenyl Group Treated with the appropriate Wittig reagent, aldehydosugar derivatives ( 1–13 ) led in good to excellent yields to the expected gem-difluoro, gem-chlorofluoro-and/or gem-dichloroenoses ( 14–29 ). Examples of their dibromo analogues had been previously described (see e.g. [1]) but the diiodo derivatives could not be isolated, The influence of the conditions on the yields is reported as well as spectroscopic properties (particularly the long-range ¹³C, ¹⁹F- and ¹H, ¹⁹F-coupling constants) of these new enoses.     

Enaminosucres et sucres halogénoacétyléniques. Communication préliminaire

Enamino- and Halogenoacetylenic sugars Traitment of an aldehydosugar ( 1 ) with secondary amines gave in an essentially quantitative yield the expected enamines ( 4–6 ). Chloro- and bromo-acetylenic sugars ( 11–14 ) were obtained in good yields by reacting with lithium methylphenylamide the corresponding gem-dihalo-olefinic sugars ( 7–10 ), whereas a Z-gem-fluoro-enamine ( 17 ) was formed when the difluoro-olefinic sugar 15 was submitted to the same reaction. The fluoro-enamine 17 is a useful synthetic intermediate allowing the preparation of several kinds of C-glycosylic compounds bearing heterocycles like isoxazole, chromone or coumarin.     

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.     

Synthèse par cyclisation nucléophile de dérivés de sucres portant un hétérocycle inséré en spiro. Note de Laboratoire

Synthesis of Sugar Derivatives Bearing a Spiro Heterocycle via Nucleophilic Cyclization Treated with the 1,4-binucleophiles 1,2-diaminoethane, 2-aminoethanol, 2-aminoethanethiol, L -cysteine, o-phenylenediamine, o-aminophenol or o-aminothiophenol the ketosugar derivative 1 gave in good yields the corresponding spiro derivatives 2–8 . In each case, the reaction was stereospecific leading to the isomer bearing the N-atom on the endo face of the bicyclic starting material. Starting from the sugar enone 9 , the aromatic 1,4-binucleophiles led stereospecifically to the spirobenzo [b]-diazepine 10 , -oxazepine 11 or -thiazepine 12 . In one case, an imine (13) was isolated. As 13 cyclized to 6 , the intermediate formation of these kind of derivatives could be considered as a common step for all these reactions.     

Synthèse de composés cyclopentaniques chiraux,di, tri et tétrasubstitués. Application à la synthèse de dérivés Oxa-13-prostanoïques

The cyclopentenecarbaldehyde 1a , acetals 2a , 2b and the cyclopentenone 2c have been transformed through regio and stereocontrolled reactions into a variety of enantiomerically pure substituted cyclopentanes. Using appropriately selected Wittig reagents, aldehyde 1a furnished the condensation products 3 , 4 , 5 . Michael addition of diethyl malonate on the α,β-unsaturated aldehyde 1a under phasetransfer conditions led efficiently to 7 . Reduction of the cyclopentenone 2c gave 21 in high yield. The cyclopentenes 2a , 2b and 23 , submitted to hydroboration-oxidation furnished the cyclopentanols 10 , 13 and 24 , respectively, in 30, 70 and 50% yields, reflecting the substitution pattern of the starting alkenes. The salient feature of these reactions is the stereospecificity due to the chiral centre of the molecules 1a , 2a , 2b and 2c , leading to compounds with two, three and four asymmetric centres. The straightforward synthesis of 11α-hydroxy-13-oxaprostanoic acid 20 is described and an approach towards the preparation of 9α, 11α-dihydroxy-13-oxaprostanoic acid 34 is also presented. The structure of these products has been determined by ¹H- and ¹³C-NMR spectroscopy.     

Chimie et pharmacologie de l'apiose III. Synthèse et propriétés de l'hydrate de l'O-isopropylidène-1, 2-tétrosulo-3-furannose

Ruthenium tetroxide oxidation of 1, 2-O-isopropylidene-β-D -threofuranose affords, besides the known 1, 2-O-isopropylidene-α-L -glycero-tetros-3-ulofuranose, a lactone. The tetrosulose is easily hydrated to the corresponding gem-diol whose dehydration on molecular sieves leads to a branched-chain dimer. Lead tetraacetate oxidation of 1, 2-O-isopropylidene-α-L -glycero-tetros-3-ulofuranose p-nitrophenylhydrazone leads quantitatively, to a gem-azoacetate, a new synthetic intermediate in carbohydrate chemistry. The 3-O-acetyl-1, 2-O-isopropylidene-α-L -glycero-tetr-3-enofuranose is easily obtained from the gem-diol. A highly stereoselective procedure is described to prepare the 3-O-acetyl-1, 2-O-isopropylidene-α-L -3, 4-exo-D₂-erythrofuranose.     

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.     

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.     

C-nucleosides aminoisoxazoliques. Communication préliminaire

Aminoisoxazoles C-nucleosides Upon treatment with bromocyanomethylenetriphenylphosphorane, a series of aldehydosugar derivatives gave in good to excellent yields the corresponding terminal gem-bromocyanoenoses 3 , 7–10 and 16 . Reacted with hydroxylamine, these unsaturated sugars led to the expected [3] 5-amino-3-glycosylisoxazoles 4 , 11 , 12 and 17 , whereas using hydroxyurea as a binucleophile they gave the corresponding 3-amino-5-glycosylisoxazoles 13 and 14 as previously described in other series [3]. The major interest of these compounds rests in their being close analogs (or enantiomers of analogs) of important biological compounds as f.e. AICAR.     

Dérivés du C-méthyl-3-xylofurannose

3-C-Methylxylofuranose Derivatives 3′-C-methyladenosine has been known for almost ten years whereas its 3′-epimer is still to be prepared, because of the difficulty of synthesizing the 3-C-methylxylo-furanose. In this communication, the synthesis of 1,2-O-isoproypylidene acetal 9 and its derivatives is described. Vicinal dihydroxylation of 5-O-benzoyl-3-deoxy-1,2-O-isopryopylidene-3-C-methylidene-α-D -erythro-pentofuranose ( 6 ) led to the branchedchain sugar derivative 7 which was selectively tosylated to 8 whose reduction gave 9 . These reactions, as well as the derivatizations of 7 , 8 and 9 , took place with good to excellent yields.     

Synthesis and Reactions of Some New Benzo[a]phenothiazine‐3,4‐dione Derivatives

The reaction of 2,3‐dihydro‐2,3‐epoxy‐1,4‐naphthoquinone ( 4 ) with substituted anilines furnished the corresponding benzo[fused]heterocyclic derivatives 5 , 6 , 6a , 6b , 7 , 8 . Furthermore, treatment of benzo[a]phenothiazine derivative 7 with halo compounds, namely, ethyl bromoacetate, phenacyl bromide, dibromoethane, or chloroacetone afforded ether derivatives 11 , 12 , 13 , 14 , respectively. Moreover, the reaction of 11 with o‐substituted aniline gave the corresponding benzo[a]phenothiazin‐5‐one derivatives 15 , 16 , 17 and benzo[d][1,3]oxazin‐4‐one 18 , respectively. Finally, the chromenone derivative 19 was synthesized via the reaction of ester derivative 11 with salicyaldhyde in refluxing pyridine. The newly synthesized compounds were characterized by spectroscopic measurements (IR, ¹H NMR, ¹³C NMR, and mass spectra).     

Synthesis of some new bipyridines,thieno[2,3‐b]pyridines,and pyrazolo[3,4‐b]pyridines

Cyclocondensation of cyanoacetamide and cyanothioacetamide with sodium salt of 3‐hydroxy‐1‐(pyridin‐3‐yl)prop‐2‐en‐1‐one gave 6‐oxo‐[2,3′]bipyridine 5a and 6‐thioxo‐[2,3′]bipyridine 5b derivatives, respectively. Compound 5b upon treatment with different methylenes 8 gave thieno[2,3‐b]pyridines 10 . Treatment of 5b with iodomethane gave bipyridine derivative 7 , which cyclocondensed with hydrazines 11 to give pyrazolo[3,4‐b]pyridines 13 . J. Heterocyclic Chem., (2012).     

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.     

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.     

New Synthetic Bromination Procedures for Use in Radiolabelling-Chemistry: Reaction of C-Metallated Derivatives of Carbohydrates with Bromide,in the Presence of Mild Oxidizing Agents

In the presence of 2 mol-equiv. of AcONa, both triglycosylborane 1 and dicyclohexylglycosylborane 2 readily react with bromine chloride generated in situ from bromide and N-chlorosuccinimide (NCS) to give the bromo-sugar 3 (75 and 60%, resp.). The use of the BH₃-THF/bromide/NCS/2 AcONa procedure permits the rapid, face-specific synthesis of 6 (58% uptake of bromine) and face-selective synthesis of 8/9 (71% uptake of bromine), from vinyl ether derivatives 5 and 7 , respectively. The dicyclohexylborane/bromide/NCS/2 AcONa procedure leads to the fast and quantitative conversion of 11 to the bromosugar 12 (91%). Hydroboration-transmetallation sequences give access to C-mercuriated carbohydrates 13 (71%) and 14 (78%). The bis(glycosyl)mercury derivative 13 is spontaneously cleaved by reaction with one equivalent of bromide/chloramine-T/aqueous HCl-solution to give 3 (87%) and 14 (76%). Hydrostannylation of acetylenic sugar 15 gave the (E)-stannylvinyl derivative 16 as the major product. This latter precursor 16 is spontaneously cleaved by the bromide/chloramine-T/aqueous HCl-solution reagent to give the bromovinyl-sugar 17 (96%).     

Utlisation d'ylides du phosphore en chimie des sucres. XIII. Synthèse de dérivés des hydroxyméthyl-3-D-glucose et-D-galactose et de composés voisins

The treatment of the 1, 2:5, 6-di-O-isopropylidene-α-D -ribo- and xylo-hexofuranos-3-uloses with cyanomethylenetriphenylphosphorane led in each case, and in almost quantitative yields, to a pair of geometrical isomers of C-cyanomethylenic sugars having respectively the ribo and the xylo configurations. Permanganate oxidation of these branched-chain unsaturated sugars afforded the corresponding gem-hydroxyformyl compounds bearing the formyl group on the more hindered face of the molecule. The formyl group of these sugars is easily derivatized to an oximino or reduced to a hydroxymethyl. The configuration at the new asymmetric carbon has been established by comparison with known compounds or by synthesis of a C(3) epimer by the classical route involving a Grignard reagent.     

Etude Conformationnelle par Résonance Magnétique Nucléaire Protonique des Dérivés de la O-Isopropylidène-2′,3′ Adénosine

Conformational analysis using ¹H n.m.r. data (δ, ³J and NOE) has been carried out on several derivatives of 2′,3′,-O-isopropylideneadenosine bearing various substituents at positions C-5′, C-8 and N-6. Conformational modifications are assigned to specific interactions between the sugar and purine moieties and also to solvent effects.