Routes to higher-carbon sugar derivatives having keto-acetylenic and -alkenic,and α,β-unsaturated aldehyde functionality

Oxidative dimerization of 7,8-dideoxy-1,2:3,4-di-O-isopropylidene-d-glycero-α-d-galacto-oct-7-ynopyranoside (1) gave a high yield of the diyne 2, readily reduced by lithium aluminum hydride to the trans,trans-diene (4). The structures of 2 and 4 were established spectroscopically and by degradation of 4 to d-glycero-d-galacto-heptitol (perscitol). A mixture of the alkyne 1 and its 7-epimer 10 was readily oxidized by dimethyl sulfoxide-acetic anhydride to the 6-ketone 11, and the 8-alkene analog was similarly prepared from the alkenes derived from 1 and 10. Likewise, oxidation of 6,7-dideoxy-1,2-O-isopropylidene-α-d-gluco(and β-L-ido)-hept-6-enopyranose gave the corresponding 5-ketone. The acetylenic ketone 11 gave a crystalline oxime and (2,4-dinitrophenyl)hydrazone, the latter being accompanied by the product of attack of the reagent at the acetylene terminus (C-8). Previous work had shown that formyl-methylenetriphenylphosphorane did not convert 1,2:3,4-di-O-isopropylidene-6-aldehydo-α-d-galacto-hexodialdo-1,5-pyranose into the corresponding C₈ unsaturated aldehyde, although the latter was obtainable via1 and 10 by an ethynylation-hydroboration sequence. The Wittig route with formylmethylenetriphenylphosphorane is shown to be satisfactory for obtaining C₇ unsaturated aldehydes from 3-O-benzyl-1,2-O-isopropylidene-5-aldehydo-α-d-xylo-pentodialdo-1,4-furanose (22) and the 3-epimer of 22, respectively. These reactions provide convenient access to higher-carbon sugars and chiral dienes for synthesis of optically pure products of cyclo-addition reactions.     

Dr. Horace S. Isbell

Addition of ethyl isocyanoacetate in strongly basic medium to the glycosuloses 1,2:5,6-di-O-isopropylidene-α-d-ribo-hexofuranos-3-ulose (1) and 1,2-O-isopropylidene-5-O-trityl-d-erythro-pentos-3-ulose (2) gave the unsaturated derivatives (E)- and (Z)-3-deoxy-3-C-ethoxycarbonyl(formylamino)methylene-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (3 and 4), and (E)-3-deoxy-3-C-ethoxycarbonyl(formylamino)methylene-1,2-O-isopropylidene-5-O-trityl-α-d-ribofuranose (5). In weakly basic medium, ethyl isocyanoacetate and 1 gave 3-C-ethoxycarbonyl(formylamino)methyl-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (12) in good yield. The oxidation of 3 and 4 with osmium tetraoxide to 3-C-ethoxalyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (17), and its subsequent reduction to 3-C-(R)-1′,2′-dihydroxyethyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (18) and its (S) epimer (19) and to 3-C-(R)-ethoxycarbonyl(hydroxy)methyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (21) and its (S) epimer (22) are described. Hydride reductions of 12 yielded the corresponding 3-C-(1-formylamino-2-hydroxyethyl), 3-C-(2-hydroxy-1-methylaminoethyl), and 3-C-(R)-ethoxycarbonyl(methylamino)methyl derivatives (13, 14 and 16). Catalytic reduction of 3 and 4 yielded the 3-deoxy-3-C-(R)-ethoxycarbonyl-(formylamino)methyl derivative 6 and its 3-C-(S) epimer. Further reduction of 6 gave 3-deoxy-3-C-(R)-(1-formylamino-2-hydroxyethyl)-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (23) which was deformylated with hydrazine acetate to 3-C-(R)-(1-amino-2-hydroxyethyl)-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (24). The configurations of the branched-chains in 16, 21, and 22 were determined by o.r.d.     

Studies on dehydro-l-ascorbic acid 3-oxime 2-phenylhydrazone: Conversion into substituted triazoles

l-threo-2,3-Hexodiulosono-1,4-lactone 3-oxime 2-(phenylhydrazone) (1) gave 2-(p-bromophenyl)-4-(l-threo-1,2,3-trihydroxypropyl)-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone (2), and this gave a diacetyl and a dibenzoyl derivative. On treatment of 2 with liquid ammonia, methylamine, or dimethylamine, the corresponding triazole-5-carboxamides (5–7) were obtained. Periodate oxidation of 5 gave 2-(p-bromophenyl)-4-formyl-1,2,3-triazole-5-carboxamide (10), and, on reduction, 10 gave 2-(p-bromophenyl)-4-(hydroxymethyl)-1,2,3-triazole-5-carboxamide, characterized as its monoacetate. Condensation of 10 with phenylhydrazine gave the triazole hydrazone. Acetonation of 2 gave the isopropylidene derivative. Reaction of 2 with HBr-HOAc gave 4-(l-threo-2-O-acetyl-3-bromo-1,2-dihydroxypropyl)-2-(p-bromophenyl)-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone. Similar treatment of 1 with HBr-HOAc gave 5-O-acetyl-5-bromo-6-deoxy-l-threo-2,3-hexodiulosono-1,4-lactone 3-oxime 2-(phenylhydrazone). This was converted into 4-(l-threo-2-O-acetyl-3-bromo-1,2-dihydroxypropyl)-2-phenyl-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone on treatment with boiling acetic anhydride. On reaction of 1 with benzoyl chloride in pyridine, dehydrative cyclization occurred, with the formation of 4-(l-threo-2,3-dibenzoyloxy-1-hydroxypropyl)-2-phenyl-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone, which was converted into the amide on treatment with ammonia.     

Preparation of derivatives on l-idose and l-iduronic acid from 1,2-O-isopropylidene-χ-Dglucofuranose by way of acetylenic intermediates

The products (1) from the periodate oxidation of 1,2-O-isopropylidene-α-D-glucofuranose were converted by ethynylmagnesium bromide into a separable, 14:11 mixture of 6,7-dideoxy-1.2-O-isopropylidene-β-L-ido-hept-6-ynofuranose (2) and its α-D-gluco analog 3. These crystalline products were further characterized as their respective 3,5-diacetates (5 and 7) and 3,5-dibenzoates (4 and 6). Ozonolysis of 2 and 3 led to 1,2-O-isopropylidene-β-L-idofuranurono-6,3-lactone (8) and its α-D-gluco analog 9, respectively; similar ozonolysis of the dibenzoates 4 and 6, followed by treatment with diazomethane, gave methyl 3,5-di-O-benzoyl-1,2-O-isopropylidene-α-L-idofuranuronate (10) and its α-D-gluco analog 11, respectively. Diborane reduction of the ozonolysis products from 4 gave 1,2-O-isopropylidene-β-L-idofuranose (13) as its 3,5-dibenzoate (12), and a similar sequence was performed with 6. The propargylic alcohols 2 and 3 were reduced by lithium aluminum hydride, in high yield, to the allylic alcohol analogs 15 and 16, further characterized as their 3,5-dibenzoates 17 and 18; compounds 15 and 16 were also obtainable by vinylation of compounds 1. The two series of derivatives in this work, epimeric at C-5, were examined comparatively by polarimetry and p.m.r. spectroscopy.     

Photochemical conversion of sugar dimethylthio-carbamates into deoxy sugars

Protected sugar derivatives having one free hydroxyl group may be deoxygenated at the alcoholic position by ultraviolet irradiation of the corresponding dimethylthiocarbamic esters: a concomitant process leads also to the original alcohol. Thus, on photolysis, the 6-dimethylthiocarbamate (1) or 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (3) gives 6-deoxy- 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (2) together with 3. Likewise, the 4-dimethylthiocarbamate (6) of 1,6-anhydro-2.3-O-isopropylidene-β-D-mannopyranose (8) gives a mixture of the 4-deoxy derivative 7 and the alcohol 8. 3-Deoxy-1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofuranose (10) was obtained by irradiation of 3-O-(dimethylthiocarbamoyl)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (9), and was accompanied by 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (11). The 3-deoxy-3-iodo analog (14) of 11 underwent conversion into 10 by photolysis, and the deoxy sugar 10 was also prepared from 3,3'-dithiobis(1,2:5,6-di-O-isopropylidene-α-D--glucofuranose) (12) by the action of Raney nickel. Photolysis of the 2-dimethylthiocarbamate (16) of methyl 3,4-O-isopropylidene-β-L-arabinopyranoside (18) gave the 2-deoxy derivative (17), together with the parent alcohol 18, and the same pair of products was obtained by the action of tributylstannane on the 2-(methylthio)thiocarbonyl derivative (19) of 18, although the dimethylthiocarbamate 16 was unreactive toward tributylstannane.     

2′-Azido-2′-deoxy- and 2′-amino-2′-deoxy-β-d-arabino-furanosyl purine nucleosides

A general method for the preparation of 2′-azido-2′-deoxy- and 2′-amino-2′-deoxyarabinofuranosyl-adenine and -guanine nucleosides is described. Selective benzoylation of 3-azido-3-deoxy-1,2-O-isopropylidene-α-d-glucofuranose afforded 3-azido-6-O-benzoyl-3-deoxy-1,2-O-isopropylidene-α-d-glucofuranose (1). Acid hydrolysis of 1, followed by oxidation with sodium metaperiodate and hydrolysis by sodium hydrogencarbonate gave 2-azido-2-deoxy-5-O-benzoyl-d-arabinofuranose (3), which was acetylated to give 1,3-di-O-acetyl-2-azido-5-O-benzoyl-2-deoxy-d-arabinofuranose (4). Compound 4 was converted into the 1-chlorides 5 and 6, which were condensed with silylated derivatives of 6-chloropurine and 2-acetamido-hypoxanthine. The condensation reaction gave α and β anomers of both 7- and 9-substituted purine nucleosides. The structures of the nucleosides were determined by n.m.r. and u.v. spectroscopy, and by correlation of the c.d. spectra of the newly prepared nucleosides with those published for known purine nucleosides.     

Synthesis of 2- (and 6-) -dithian-2-yluracil nucleosides and their conversion into nucleoside derivatives

Addition of 2,2′-anhydro-[1-(3-O-acetyl-5-O-trityl-β-D-arabinofuranosyl)uracil] (1) to excess 2-litho-1,3-dithiane (2)in oxolane at ?78° gave 2-(1,3-dithian-2-yl)-1-(5-O-trityl-β-D-arabinofuranosyl)-4(1H)pyrimidinone (3), O²,2′-anhydro-5,6-di-hydro-6-(S)-(1,3-dithian-2-yl)-5′-O-trityluridine (4), and 2-(1,4-dihydroxybutyl)-1,3-dithiane (5) in yields of 15, 30, and 10% respectively. The structure of 3 was proved by its hydrolysis in acid to give 2-(1,3-dithian-2-yl)-4-pyrimidinone (6) and arabinose, and by desulfurization with Raney nickel to yield the known 2-methyl-1-(5-O-trityl-β-D-arabinofuranosyl)-4(1H)-pyrimidinone (7). Detritylation of 3 without glycosidic cleavage could only be effected by prior acetylation to 1-(2,3-di-O-acetyl-5-O-trityl-β-D-arabinofuranosyl)-2-(1,3-dithian-2-yl)-4(1H)-pyrimidinone (8) which, after treatment with acetic acid at room temperature for 65 h followed by the action of sodium methoxide gave 2-(1,3-dithian-2-yl)-1-β-D-arabinofuranosyl-4(1H)-pyrimidinone (10) in 45% yield. Detritylation of 4 in boiling acetic acid gave 5,6-dihydro-6-(S)-(1,3-dithian-2-yl)-1-β-D-arabinofuranosyluracil (12) and 3-[(S)-1-(1,3-dithian-2-yl)]propionamido-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxazolidinone (13) in 10 and 90% yields, respectively. When 12 was kept in water or methanol for 7 days, quantitative conversion into 13 occurred. Acid hydrolysis of 12 afforded arabinose and 5,6-di-hydro-6-(1,3-dithian-2-yl)uracil (14), which was desulfurized with Raney nickel to the known 5,6-dihydro-6-methyluracil (15). Treatment of 13 with trifluoroacetic anhydride-pyridine yielded 77% of the cyano derivative 17. Similar dehydration of 3-(R)-1-methylpropionamido-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxalidinone (18), obtained by desulfurization of 13, gave 60% of the nitrile 19. Hydrogenation of 19 over platinum oxide in acetic anhydride gave the acetamide derivative 20 in 95% yield. Nitrobenzoylation of 13 gave 3-[(S)-1-(1,3-dithian-2-yl)]cyanomethyl-3,5-di-O-p-nitrobenzoyl-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxazolidinone (22), which was converted in 37% yield by treatment with methyl iodide in dimethyl sulfoxide into the aldehyde 24, characterized as the semicarbazone 25. The purification of 5 and its characterization as 2-(1,4-di-O-p-nitrobenzoylbutyl)-1,3-dithiane (27) is described.     

Über die Synthese partiell benzylierter Zucker

1,2:5,6-Di-O-isopropylidene-α-D-allofuranose (1), 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (2), and 1,2.3,4-di-O-isopropylidene-α-D-galactopyranose (3) have been separately treated in pyridine solution with trifluoromethanesulphonic anhydride, 2,2,2-trifluoroethanesulphonyl chloride, and pentaflucrobenzenesulphonyl chloride. Both 1 and 2 afforded the anticipated sulphonic esters. Although 3 also gave the 2,2,2-trifluoroethanesulphonic and pentafluorobenzenesulphonic esters, the reaction with trifluoromethanesulphonic anhydride yielded 6-deoxy-1,2:3,4-di-O isopropylidene-6-pyridino-α-D-galactopyranose trifluoromethanesulphonate.     

Synthetic mucin fragments. Methyl 6-O-(2-acetamido-2-deoxy-β-D-glycopyranosyl)-β-D-galactopyranoside,methyl 3,4-di-O-(2-acetamido-2-deoxy-β-D-glycopyranosyl)-β-D-galactopyranoside,and methyl O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1 å 3)-O-β-D-galactopyranosyl-(1 å 3)-O-(2-acetamido-2-deoxy-β- D-glucopyranosyl)-(1 å 3)-β-D-galactopyranoside

Condensation of methyl 2,6-di-O-benzyl-β-d-galactopyranoside with 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-d-glucopyrano)-[2,1,-d]-2-oxazoline (1) in 1,2-dichloroethane, in the presence of p-toluenesulfonic acid, afforded a trisaccharide derivative which, on deacetylation, gave methyl 3,4-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-2,6-di-O-benzyl-β-d- glactopyranoside (5). Hydrogenolysis of the benzyl groups of 5 furnished the title trisaccharide (6). A similar condensation of methyl 2,3-di-O-benzyl-β-d-galactopyranoside with 1 produced a partially-protected disacchraide derivative, which, on O-deacetylation followed by hydrogenolysis, gave methyl 6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-β-d-glactopyranoside (10). Condensation of methyl 3-O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-benzyl-β-d- galactopyranoside with 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-acetyl-α-d-galactopyranosyl bromide in 1:1 benzene-nitromethane in the presence of powdered mercuric cyanide gave a fully-protected tetrasaccharide derivative, which was O-deacetylated and then subjected to catalytic hydrogenation to furnish methyl O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→3)-O-β-d-galactopyranosyl-(1å3)-O-(2-acetamido-2-deoxy- β-d-glucopyranosyl)-(1å3)-β-d-galactopyranoside (15). The structures of 6, 10, and 15 were established by ¹³C-n.m.r. spectroscopy.     

An approach to the synthesis of branched-chain amino sugars from c-methylene sugars

The reaction of 1,2:5,6-di-O-isopropylidene-3-C-methylene-α-D-ribo-hexofuranose (4) with mercuric azide in hot 50% aqueous tetrahydrofuran yielded, after reductive demercuration, 3-azido-3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-methyl-α-D-glucofuranose (5). Partial, acid hydrolysis of5 afforded the diol7, which gave 3-azido-3-deoxy-1,2-O-isopropylidene-5,6-di-O-methanesulphonyl-3-C-methyl-α-D-glucofuranose (8) on sulphonylation. On hydrogenation over a platinum catalyst and N-acetylation, the dimethanesulphonate 8 furnished 3,6-acetylepimino-3,6-dideoxy-1,2-O-isopropylidene-5-O-methanesulphonyl-3-C-methyl-α-D-glucofuranose (9), which was also prepared by an analogous sequence of reactions on 3-azido-3-deoxy-1,2-O-isopropylidene-5-O-methanesulphonyl-3-C-methyl-6-O-toluene-p-sulphonyl-α-D-glucofuranose (13). The formation of the N-acetylepimine 9 establishes the D-gluco configuration for 5.1,2-O-Isopropylidene-3-C-methylene-α-D-ribo-hexofuranose (20) reacted with mercuric azide in aqueous tetrahydrofuran at ≈85° to give 3,6-anhydro-1,2-O-isopropylidene-3-C-methyl-α-D-glucofuranose (22) as a result of intramolecular participation by the C-6 hydroxyl group in the initial intermediate.     

Synthesis of branched-chain sugar derivatives related to aldgarose

Ethynylation of 1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofuranos-3-ulose (1) gave the 3-C-ethynyl allo derivative 2, together with an adduct (3) resulting from interaction of two molecules of 1 with one of acetylene. Lithium aluminum hydride reduced the acetylenes 2 and 3 to the corresponding alkenes 4 and 8; on sequential ozonolysis-borohydride reduction, these both gave 3-C-(hydroxymethyl)-1,2:5,6-di- O-isopropylidene-α-D-allofuranose (6), further characterized as its 3,3¹-cyclic carbonate 9. Ozonolysis of the acetylene 2 gave the 3¹,5-lactone (5) of the 3-C-carboxy analog, thus establishing the stereochemistry of 2, which was independently established by n.m.r. spectroscopy employing a lanthanide shift-reagent. Treatment of 2 with mercuric acetate in ethyl acetate, followed by hydrogen sulfide, gave a mixture of the 3-C-acetyl-3-O-acetyl derivative 10 and a product (11) derived from internal cyclization of 5,6-deacetonated, O-deacetylated 10. Reduction of 10 with lithium aluminum hydride gave a separable mixture of diastereoisomeric 3-C-(l-hydroxy-ethyl) derivatives (12a, 12b) that were individually converted into their corresponding 3,3¹-cyclic carbonates 13a and 13b, products that contain the branch functionality of the unusual, branched-chain sugar aldgarose.     

Synthesis of some derivatives of pseudo-α-galactopyranose [(1,2/3,4,5)-5-hydroxymethyl-1,2,3,4-cyclohexanetetrol]

Isopropylidenation of dl-(1,2/3,4,5)-5-hydroxymethyl-1,2,3,4-cyclohexanetetrol (1) with 2,2-dimethoxypropane in N,N-dimethylformamide in the presence of toluene-p-sulfonic acid gave the 1,2:3,4-, 1,2:4,7-, and 2,3:4,7-di-O-isopropylidene derivatives. Several C-7 substituted derivatives of 1 of biological interest have been prepared by nucleophilic displacement reactions of the tosylate derived from the most readily available 1,2:3,4-di-O-isopropylidene derivative 3. Condensation of 3 with 2,3,4,6-tetra-O-acetyl-α-d-glucopyranosyl bromide gave diastereoisomeric products, which were converted into 7-O-(β-d-glucopyranosyl)-pseudo-α-d- (26a) and -d-galactopyranose (26B), the structures of which were confirmed by degradation of the octa-acetate of 26A, yielding the known pseudo-α-d-galactopyranose penta-acetate.     

Branched-chain amino sugars. stereospecific synthesis of 3-C-(2-acetamidoethyl)-3-deoxy-1,2-O-isopropylidene-β-l-lyxofuranose

Condensation of 1,2:5,6-di-O-isopropylidene-α-d-xylo-hexofuranos-3-ulose (1) with diethyl cyanomethylphosphonate afforded a mixture of the cis- and trans-3-cyanomethylene-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-xylo-hexofuranoses (2) in 80% yield. Catalytic reduction of 2 yielded 3-C-cyanomethyl-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-gulofuranose (4) exclusively. Palladium and hydrogen was found to rearrange the exocyclic double bond of 2 to give the 3,4-ene (3). Catalytic reduction of 3 also proceeded stereospecifically to yield 4. Selective hydrolysis of 4 yielded the diol 5, which was cleaved with periodate and the product reduced with sodium borohydride to afford crystalline 3-C-cyanomethyl-3-deoxy-1,2-O-isopropylidene-β-l-lyxofuranose (6) in 87% yield. Catalytic reduction of the latter with hydrogen and platinum in the presence of acetic anhydride and ethanol gave the crystalline l-amino sugar, 3-C-(2-acetamidoethyl)-3-deoxy-1,2-O-isopropylidene-β-l-lyxofuranose (7) in 92% yield.     

Synthesis of dl-penta-N,O-acetylvaliolamine and related branched-chain aminocyclitols

Valiolamine (1), a branched-chain aminocyclitol α-d-glucosidase inhibitor, has been synthesised as the racemic penta-N,O-acetyl derivative (10) from dl-(1,3/2,4)-1,2,3-triacetoxy-4-bromo-6-methylenecyclohexane (2). Epoxidation of 2 with m-chloroperbenzoic acid, followed by hydrolysis and acetylation, gave exclusively dl-(1,2,4/3,5)-2,3,4-triacetoxy-1-C-acetoxymethyl-5-bromocyclohexanol (4), from which 10 was obtained by azidolysis in N,N-dimethylformamide, and successive catalytic hydrogenation and acetylation. In contrast, azidolysis in aqueous 2-methoxyethanol gave dl-(1,2,4/3,5)-2,3,4-triacetoxy-1-C-acetoxymethyl-5-azidocyclohexanol, which was converted into the 5-epimer of 10. Hydroxylation of 2 with osmium tetraoxide and hydrogen peroxide, followed by acetylation, gave the 1-epimer (6) of 4. The 1,5-diepimer of 10 was prepared from 6 by the same sequence.     

Studies on dehydro-l-ascorbic acid 2-arylhydrazone 3-oximes: Conversion into substituted triazoles and isoxazolines

l-threo-2,3-Hexodiulosono-1,4-lactone 2-(arylhydrazones) (2) were prepared by condensation of dehydro-l-ascorbic acid with various arylhydrazines. Reaction of 2 with hydroxylamine gave the 2-(arylhydrazone) 3-oximes (3). On boiling with acetic anhydride, 3 gave 2-aryl-4-(2,3-di-O-acetyl-l-threo-glycerol-l-yl)-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones (4). On treatment of 4 with liquid ammonia, 2-aryl-4-(l-threo-glycerol-l-yl)-1,2,3-triazole-5-carboxamides (5) were obtained. Acetylation of 5 with acetic anhydride-pyridine gave the triacetates, and vigorous acetylation with boiling acetic anhydride gave the tetraacetyl derivatives. Periodate oxidation of 5 gave the 2-aryl-4-formyl-1,2,3-triazole-5-carboxamides (8), and, on reduction, 8 gave the 2-aryl-4-(hydroxymethyl)-1,2,3-triazole-5-carboxamides, characterized as the monoacetates and diacetates. Controlled reaction of 2 with sodium hydroxide, followed by neutralization, gave 3-(l-threo-glycerol-l-yl)-4,5-isoxazolinedione 4-(arylhydrazones), characterized by their triacetates. Reaction of 2 with HBr-HOAc gave 5-O-acetyl-6-bromo-6-deoxy-l-threo-2,3-hexodiulosono-1,4-lactone 2-(arylhydrazones); these were converted into 4-(2-O-acetyl-3-bromo-3-deoxy-l-threo-glycerol-l-yl)-2-aryl-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones on treatment with acetic anhydride-pyridine.     

4-deoxy-4-fluoro-1,2-O-isopropylidene-β-D-xylo-hexulopyranose

A 5-stage synthesis of the title compound (11), the first example of a secondary deoxyfluoroketose, is described. The synthesis comprised the following reaction sequence: D-fructose→1,2:4,5-di-O-isopropylidene-β-D-fructopyranose (4)→1,2:4,5-di-O-isopropylidene-3-O-tosyl-β-D-fructopyranose (3)→ 3,4-anhydro-1,2-O-isopropylidene-β-D-ribo-hexulopyranose (9)→4-deoxy-fluoro-1,2-O-isopropylidene-β-D-xylo-hexulopyranose (11). Fluoride displacement at C-4 in 9 was effected with tetrabutyl-ammonium fluoride in methyl cyanide. Similar treatment of either 3 or 1,2:4,5-di-O-isopropylidene-3-O-tosyl-β-D-ribo-hexulopyranose (5) failed to yield a fluoro derivative. Compound 5 was prepared by the sequence 4→1,2:4,5-di-O-isopropylidene-β-D-erythro-hexo-2,3-diulopyranose (6)→1,2:4,5-di-O-isopropylidene-β-D-ribo-hexulopyranose (7)→5.     

The synthesis and N.M.R. spectroscopy of derivatives of 6-amino-6-deoxy-D-galactose-6-15N

Derivatives of 6-amino-6-deoxy-D-galactose-6-¹⁵N have been synthesized by reaction of the 6-deoxy-6-iodo (1) or 6-O-p-tolylsulfonyl derivative of 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose with potassium phthalimide-¹⁵N. The reaction of 1 also yielded an elimination product, 6-deoxy-1,2:3,4-di-O-isopropylidene-β-L-arabino-hex-5-enopyranose. The structures of the 6-amino-6-deoxy-D-galactose derivatives and their precursors were characterized by proton- and ¹³C-n.m.r. spectroscopy, with confirmation of the ¹³C assignments by selective proton decoupling. Selective broadening of the C-1, C-4, C-5, and C-6 resonances of 6-amino-6-deoxy-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose by low concentrations of cupric ion was observed, and studied by computerized measurements of the ¹³C linewidths. The application of this broadening to ¹³C-spectral assignments of amino sugar derivatives is indicated.     

A fused pyrrolidotriazole derivative from bis(ethylsulphonyl)-(2,3-O-isopropylidene-4-O-methanesulphonyl-α-D-lyxopyranosyl)methane

Reaction of bis(ethylsulphonyl)-(2,3-O-isopropylidene-4-O-methanesulphonyl-α-D-lyxopyranosyl)methane (1) with sodium azide in N,N-dimethylformamide gave 1(S)-hydroxymethyl-2(R),3(S)-isopropylidenedioxypyrrolido-[1,2-c]-4-ethylsulphonyl-1,2,3-triazole (5). The latter was identified by p.m.r. and mass spectrometry, and by degradation to, and unambiguous synthesis of, 4-ethylsulphonyl-1,2,3-triazole (17).     

Synthesis of higher-carbon sugars via vinyltin derivatives of simple monosaccharides

6-O-Benzyl-7,8-dideoxy-1,2:3,4-di-O-isopropylidene-l-glycero-α-d-galacto-oct-7-ynopyranose reacted with tributyltin hydride to afford (Z-6-O-benzyl-7,8-dideoxy-1,2:3,4-di-O-isopropylidene-8-(tributylstannyl)-l-glycero-α-d-galacto-oct-7-enopyranose, which was subsequently isomerized to the E-olefin 4. Replacement of the tributyltin moietey with lithium in 4 afforded the vinyl anion which reacted with 3-O-benzyl-1,2-O-isopropylidene-α-d-xylo-pentodialdo-1,4-furanose, furnishing 3-O-benzyl-6-C-[(E)-6-O-benzyl-7-deoxy-1,2:3,4-di-O-isopropylidene-l-glycero-α-d-galacto-heptopyranos-7-ylidene] -60-deoxy-1,2-O-isopropylidene-α-d-gluco- (6) and -β-l-ido-furanose (7) in yields of ∼70 or ∼87% (depending on the temperature of the reaction). The configurations of the new chiral centers in 6 and 7 were determined by their conversion into 3-O-benzyl-1,2-O-isopropylidene-α-d-gluco- and -β-l-ido-furanose, respectively. Oxidation of 6 and 7 gave the same enone, 3-O-benzyl-6-C-[(E)-6-O-benzyl-7-deoxy-1,2:3,4-di-O-isopropylidene-l-glycero-α-d-galacto- heoptopyranos-7-ylidene]-6-deoxy-1,2-O-isopropylidene-α-d-xylo-hexofuranos-5-ulose.     

Glycosyl α-amino acids : Part III. Synthesis of D- and L-2-(1,2:5,6-DI-O-isopropylidene-α-D-galactofuranos-3-YL)glycine

Stereospecific hydroxylation of (E)-3-deoxy-1,2:5,6-di-O-isopropylidene-3-C-(methoxycarbonylmethylene)-α-D-xylo-hexofuranose (2) with potassium permanganate in pyridine afforded pure 3-C-[(R)-hydroxy(methoxycarbonyl)methyl]-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose (5) in 55% yield. Mesylation of the diol 5 in pyridine yielded the monomethanesulfonate 6 and, in addition, a small proportion of an unsaturated, exocyclic sulfonate 7. Treatment of 6 with sodium azide in N-N-dimethylformamide and reduction of the resultant α-azido ester 9 afforded methyl D- (and L-) 2-(1,2:5,6-di-O-isopropylidene-α-D-galactofuranos-3-yl)glycinate, (11a) and (10a), respectively. Basic hydrolysis of 11a and 10a yielded D- and L-2-(1,2:5,6-di-O-isopropylidene-α-D-galactofuranos-3-yl)glycine (11b) and (10b), respectively. The structures of the glycosyl α-amino acids were correlated with that of L-alanine by circular dichroism.