Synthesis of some derivatives of 3-amino-3-desoxyerythrose and 3-amino-3-desoxy-D-3-erythrose

The synthesis of derivatives of 3-amino-3-deoxy-L-erythrose by LAH or LAD reduction of the oxime of 1,2-O-isopropylidene α-L -glycero-tetros-3-ulofuranose is described.     

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.     

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.     

Utilisation d'ylides du phosphore en chimie des sucres XXIII Eliminations accompagnant certaines réactions de Wittig

Some reactions of 3-O-alkyl-6-deoxy-1,2-O-isopropylidene-α-D-xylo-hexofuranos-5-uloses (1 and 2) with Wittig reagents are described. These ketosugars react with methylenetriphenylphosphorane and benzylidenetriphenylphosphorane to give the expected unsaturated branched-chain sugars and dienes formed by elimination of H–C(4) and the 3-alkyloxy group. Structural studies on all these compounds have been effected using NMR. spectroscopy and particularly, when necessary, nuclear Overhauser Effect. One important by-product of these reactions is an unsaturated ketone 3,6-dideoxy-1,2-O-isopropylidene-α-D-glycero-hex-3-enofuranos-5-ulose (6). Compounds 1 and 2 do not react with cyanomethylenetriphenylphosphorane.     

Isomérisations en chimie des sucres. II Fermetures de cycles par attaque nucléophile intramoléculaire sur des carbones sp2 à caractère électrophile: Furannoses hybridés sp2 en C3

When heated with one equivalent of H₂O, the 1,2: 5,6-di-O-isopropylidene-α-D-ribo- and -xylo-hexofuranos-3-uloses loose one molecule of acetone and yield the 3, 6-anhydro-1, 2-O-isopropylidene-α-D-ribo- and -xylo-hexofuranos-3-ulose ketohydrols. The carbonyl group of the starting material seems to provide some kind of intramolecular electrophilic assistance to the hydrolysis of the 5, 6-O-isopropylidene group. When the oxygen of the carbonyl group is replaced by cyanomethylene, an analogous cyclisation takes place under base catalysis, provided that C6 bears a free hydroxyl group.     

Utilisation d'ylides du phosphore non stabilisés en chimie des sucres. V. Sucres ramifiés dérivés du méthyl α-D-lyxo-hexopyrannosul-4-oside. Communication préliminaire

Cis and trans-methyl-4-deoxy-2, 3-O-isopropylidene-6-O-methyl-4-methylthio-methylene-α-D -lyxo-hexopyra-nosides are prepared by a Wittig reaction. Methods are described for the determination of the configuration of the geometrical isomers whose Raney-Nickel reduction leads to derivatives of 4-deoxy-4-methyl-hexoses of the D -manno and D -talo series.     

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,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 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.     

Application de la réaction de Wittig à la synthèse de dérivés de bromoénosuloses et d'esters bromoénuroniques. Note de laboratoire

Use of the Wittig reaction for the synthesis of derivatives of bromoenosuloses and bromoenuronic esters Treatment of 3-O-benzyl (or 3-O-methyl)-1, 2-O-isopropylidene-α-D -xylo-pentodialdo-1, 4-furanoses ( 2 or 1 ) with acetylbromomethylidenetriphenylphosphorane ( 3 ), benzoylbromomethylidenetriphenylphosphorane ( 4 ) or bromoethoxycarbonylmethylidenetriphenylphosphorane ( 5 ) gave in good to excellent yields the expected enose ( 6--11 ). In all cases but one ( 8 where some 10% of the E-isomer was formed) the reaction led to the exclusive formation of the Z-isomer whose configuration was established by NMR.     

Synthèse et réactions de didésoxy-5,6-halogéno-6-α-D-xylo-hepténo-5-furannurononitriles. Communication préliminaire

Synthesis and reactions of 5,6-dideoxy-6-halogeno-α-D-xylo-hept-5-eno-furanurononitriles The 5,6-dideoxy-6-chloro-, 6-iodo- and 6-fluoro-3-O-methyl-α-D -xylo-hept-5-eno-furanurononitriles have been prepared, their properties described as well as the methods used for the assignment of the configuration of the geometrical isomers. Some new reactions of the 6-bromo analog ( 1 ) of these compounds are reported. For example, when reacted with 2-mercaptoethanol or N,N′-dimethyl-ethylenediamine in the presence of NaOH, 1 gave the corresponding six-membered ring, stereo-isomers of an oxathiane or of a perhydrodiazine respectively. When the base used was Et₃N and the binucleophile the N-methyl-ethanolamine or the N,N′-dimethyl-ethylene-diamine the major product was a cyano-enamine which could be hydrolysed to a β-cyanoketone or cyclized to a five-membered ring, an oxazolidine or an imidazolidine respectively.     

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.     

Utilisation d'ylides du phosphore en chimie des sucres. XV. Synthèse de sucres à insaturation terminale

Treatment of 3-O-benzyl-1, 2-O-isopropylidene-3-O-methyl-α-D -xylo-pentodialdlo-1,4-furanose and 2,5-anhydro-3,4-O-isopropylidene-aldehydo-D -ribose with moderately stable and stable phosphonium ylides led to the corresponding terminal-unsaturated sugars obtained as a mixture of cis and trans isomers. The cis:trans ratios were determined by ¹H-NMR. and (or) GLC. They showed that steric factors play an important role in the control of the stereochemistry of these reactions.     

Synthetic Studies on Sialoglycoconjugates 89: Synthesis of Ganglioside GM3 and KDN-GM3 Containing Different Carbon-Chain Length Fatty Acyl Groups at the Ceramide Residue

ABSTRACT

Ganglioside GM₃ and KDN-ganglioside GM₃, containing hexanoyl, decanoyl, and hexadecanoyl groups at the ceramide moiety have been synthesized. Selective reduction of the azido group in O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-O-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1→4)-O-(3-O-acetyl-2,6-di-O-benzoyl-β-D-glucopyranosyl)-(1→1)-(2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (1) and O-(methyl 4,5,7,8,9-penta-O-acetyl-3-deoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-(2→3)-O-(2,4-di-O-acetyl-6-O-benzoyl-β-D-galactopyranosyl)-(1→4)-O-(3-O-acetyl-2,6-di-O-benzoyl-β-D-glucopyranosyl)-(1→1)-(2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (2), coupling with hexanoic, decanoic, and hexadecanoic acids, O-deacylation, and de-esterification gave the title gangliosides GM₃ (11→13) and KDN-GM₃ (14→16) in good yields. On the other hand, O-deacylation of 1 and subsequent de-esterification gave 2-azido-sphingosine containing-GM₃ analogue 17, which was converted into lyso-GM₃, in which no fatty acyl group was substituted at the sphingosine residue, by selective reduction of the azido group.     

Studies on the Thioglycosides of N-Acetylneuraminic Acid. 6: Synthesis of Ganglioside GM4 Analogs1

Abstract

Two kinds of ganglioside GM₄ thioanalogs having different fatty acyl groups at the ceramide moiety, (2S, 3R, 4E)-1-O-[3-S-(5-acetamido-3,5-di-deoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-3-thio-β-D-galacto-pyranosyl]-2-octadecanamido (or -tetracosanamido)-4-octadecene-1,3-diol (12, 13), have been synthesized. Condensation of the trichloroacetimidate 7, derived from 1,2,4,6-tetra-O-acetyl-3-S-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonate)-3-thio-β-D-galactopyranose (6) by selective 1-O-deacetylation and subsequent trichloroacetimidation, with (2S, 3R, 4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (4), gave the coupling product (8), which was converted into the title compounds via selective reduction of the azide group, condensation with fatty acids, and removal of the protecting groups.     

Dérivés C-glycosyliques. XXIV. Glycosyl-4-thiazoles

4-C-glycosylthiazoles have been prepared by reacting thiourea or thioacetamide with a 6-S-benzyl-6-chloro-1,2-O-isopropylidene-3-O-methyl-α-D-xylo-6-thiohexofuranos-5-ulose (7). The latter compound which constitutes an interesting synthetic intermediate in carbohydrate chemistry has been obtained by successive oxidation and chlorination of 6-S-benzyl-1,2-O-isopropylidene-3-O-methyl-α-D-6-thioglucofuranose.     

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.     

Synthetic Studies on Sialoglycoconjugates 8: Synthesis of 8-EPI-N-Acetylenuraminic Acid Derivatives

Abstract

Methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-L-glycero-α-D-galacto-2-nonulopyranosid]onate (6) and its 8-epi-N-acetylneuraminic acid derivatives were synthesized from methyl [2-(trimethylsilyl)ethyl 5-acetamido-4,7-di-O-acetyl-3,5-dideoxy-D-glycero-α-D-galacto-2-nonulo-pyranosid]onate (1) and methyl [2-(trimethylsilyl)ethyl 5-acetamido-3,5-dideoxy-4,7-di-O-2-(trimethylsilyl)ethoxymethyl-D-glycero-α-D-galacto-2-nonulopyranosid]onate (2).     

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.     

Syntheses of 4- and/or 4′-Phosphate Derivatives of Methyl 3-O-l-Glycero-α-d-manno-heptopyranosyl-l-glyceroα-d-manno-heptopyranoside and Their 2-(4-Trifluoro-acetamidophenyl)ethyl Glycoside Analogues.

Abstract

Syntheses are described of the three disaccharides: methyl 3-O-L-glycero-α-D-manno-heptopyranosyl-L-glycero-α-D-manno-heptopyranoside 4-phosphate, methyl 3-O-(L-glycero-α-D-manno-heptopyranosyl 4-phosphate)-L-glycero-α-D-manno-heptopyranoside, and methyl 3-O-(L-glycero-α-D-manno-heptopyranosyl 4-phosphate)-L-glycero-α-D-manno-heptopyranoside 4-phosphate together with their 2-(4-trifluoroacetamidophenyl)ethyl glycoside analogues. These correspond to phosphorylated structures found in the inner core region of lipopolysaccharides from Salmonella. The known derivative methyl 6,7-di-O-acetyl-2,3,4-tri-O-benzyl-L-glycero-α-D-manno-heptopyranoside was used as a common heptose precursor. Phosphorylation on suitably protected disaccharide derivatives was performed by treatment with phosphorus triimidazolate in dichloromethane followed by the addition of benzyl alcohol and in situ oxidation with m-chloroperbenzoic acid to give the dibenzyltriester phosphate derivatives, which after deprotection gave the target compounds.