On the ring transformation of hydrazine derivatives of l-ascorbic acid into nitrogen heterocyclic derivatives

l-hreo-2,3-hexodiulosono-1,4-lactone 2-(p-methoxyphenylhydrazone) (1) was condensed with arylhydrazines to give mixed bishydrazones, whose acetylation gave the corresponding di-O-acetyl derivatives. The hydrazone 1 undergoes elimination of one molecule of water per molecule during, the acetylation, and gives 4-(2-acetoxy- ethylidene)-4-hydroxy-2,3-dioxobutano-1,4-lactone 2-(p-methoxyphenylhydrazone), which reacts with methylhydrazine, via a ring transformation process, to give 1-methyl-3-(L-methylpyrazolin-3-yl)-4,5-pyrazoledione 4-(p-methoxyphenylhydrazone). Alkali rearranged the mixed bishydrazones to 1-aryl-3-(l-threo-glycerol-1-yl)-4,5- pyrazoledione 4-(p-methoxyphenylhydrazones), which gave triacetyl and tribenzoyl derivatives, and, upon periodate oxidation, afforded 1-aryl-3-formyl-4,5- pyrazolediones 4-(p-methoxyphenylhydrazones) that gave the corresponding phenylhydrazones. The n.m.r. and mass spectra of some of these derivatives have been investigated.     

Cooperative aspects of hydrogen bonding in carbohydrates

Various compounds related to the antibacterial, sulfanilamide drugs have been prepared from dehydro-l-ascorbic acid or its d-erythro analog by reaction with hydrazines related to sulfanilamide, sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxydiazine, whereby the 2-mono- and 2,3-bis-(hydrazone) were isolated. After opening of the lactone ring in the bis(hydrazones) with alkali, nucleophilic attack, on the carbonyl group, of the imino nitrogen atom of the 3-hydrazone residue afforded 3-(l-threo-glycerol-1-yl)-1-phenyl- and -1-(p-sulfamylphenyl)-4,5-pyrazole-dione 4-(p-sulfamylphenlhydrazone) and the related 3-(d-erythro-glycerol-1-yl)compounds. Whereas acetylation of l-threo-2,3-hexodiulosono-1,4-lactone 2,3-bis(p-sulfamylphenylhydrazone) (9) and 3-(l-threo-glycerol-1-yl)-1-(p-sulfamylphenyl)-4,5-pyrazoledione 4-(p-sulfamylphenylhydrazone) (15) gave the O-acetyl derivatives, benzoylation of 15 gave the di-N-benzoy ltri-O-benzoyl compound. Reaction of 9 with cupric chloride gave 3,6-anhydro-3-(p-suIfamylphenylazo) -l-xylo-2-hexulosono-1,4-lactone 2-(p-sulfamylphenylhydrazone). The 3-(l-threo-glycerol-1-yl)-1-(p-sulfamylphenyl)flavazole (35) was prepared by the rearrangement of 3-[(1-p-sulfamylphenyl)hydrazono-l-threo-trihydroxybutyl]-2-quinoxalinont (33). Periodate oxidation of 15,33, and 35 gave 3-formyl-1-(p-sulfamylphenyl)-4,5-pyrazoledione 4-(p-sulfamylphenylhydrazone), 3-1-[(p-sulfamylphenyl)hydrazono]glyoxal-1-yl]-2-quinoxalinone, and 3-formyl-1-(p-sulfamylphenyl)flavazole, respectively. The i.r. and n.m.r. spectral data for some of these derivatives are reported.     

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.     

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.     

Reaction of dehydro-d-erythorbic acid and its aryl analogs with ortho-diamines

Condensation of 3-(d-erythro -2,3,4-trihydroxy-l-oxobutyl)-2-quinoxalinone and its 6-chloro derivative (obtained by the reaction of d-erythro-2,3-hexodiulosono-1,4-lactone with ortho-diamines) with aryl- or aroyl-hydrazines gave 3-[l-(phenylhydrazono)-d-erythro-2,3,4-trihydroxybutyl]-2-quinoxalinone (5) and relatives. Whereas boiling acetic anhydride causes the loss of two molecules of water per molecule of such hydrazones, affording, the 3-[5-(acetoxymethyl)-l-arylpyrazol-3-yl]-2-quinoxalinones, identical with those obtained from the l-threo isomer, alkali causes the loss of only one molecule, affording, the corresponding flavazoles. Periodate oxidation of 5 gave 3-[l-(phenylhydrazono)glyoxal-l-yl]-2-quinoxalinone, which afforded the corresponding mixed bis(hydrazones). A similar sequence of reactions was conducted with the aryl analogs, 4-phenyl-2,3-dioxobutano-1,4-lactone and its p-chlorophenyl derivative, whereby the 3-[2-aryl-l-(arylhydrazono)-2-hydroxyethyl]2-quinoxalinones, were prepared; these were transformed into 3-(α-hydroxybenzyl)-flavazoles that gave monoacetyl derivatives.     

Transformation of the hydrazones of 6-chloro-3-(l-threo-2,3,4-trihydroxy-1-oxobutyl)-2-quinoxalinone into other heterocyclic compounds

The difference in reactivity of the two amino groups in 4-chloro-o-phenylene-diamine allowed it to react with l-threo-2,3-hexodiulosono-1,4-lactone to give, after further reaction with various hydrazines, 6-chloro-3-(1-substituted-hydrazono-l-threo-2,3,4-trihydroxybutyl)-2-quinoxalinones (5-14), whose structures were deduced from their reactions, as well as from mass spectrometry of the (p-nitrophenyl)-hydrazone. Elimination of one mole of water per mole from these hydrazones gave the 1-aryl-6-chloro-3-(l-threo-glycerol-1-yl)flavazoles; the mass spectrum of one of these flavazoles is discussed. Elimination of two moles of water per mole from the hydrazones (5, 7, and 8) occurred with simultaneous cyclization to give 3-[l-aryl-5- (hydroxymethyl)pyrazol-3-yl]-6-chloro-2-quinoxalinones. whose acetylation gave the corresponding- monoacetyl derivatives (that could also be obtained by the action of boiling acetic anhydride on the starting hydrazones). Periodate oxidation of the hydrazones and the flavazole derivatives afforded the corresponding aldehydes (that could react with hydrazines).     

Studies on 3-epimeric l-2-hexulose phenylosazones. Structure and anomeric configuration of the 3,6-anhydro-osazone derivatives obtained from l-xylo- and l-lyxo-2-hexulose phenylosazone

Dehydration of the 3-epimeric 2-hexulose phenylosazones l-xylo-hexulose phenylosazone and l-lyxo-hexulose phenylosazone afforded 3,6-anhydro-l-lyxo-2-hexulose phenylosazone (2) as the preponderant isomer from both. The identity of 2 was obtained by t.l.c., and by acetylation followed by comparison of the products. Acetylation of 2 with acetic anhydride-pyridine afforded the di-O-acetyl derivative 4, and further acetylation gave the N-acetyldi-O-acetyl derivative 5. Refluxing of 2 with copper sulfate afforded a C-nucleoside analog, namely, 2-phenyl-4-α-l-threofuranosyl-1,2,3-osotriazole (6). The anomeric configuration was determined by n.m.r. spectroscopy. The stereochemical course of the dehydration process and the mass spectra of compounds 2, 4, 5, and 6 are discussed.     

Synthesis of some pyrazole derivatives having l-threo and d-erythro side chains

The mixed bis(arylhydrazones) of l-threo-2,3-hexodiulosono-1,4-lactone rearrange into pyrazolediones. Mono- and bis-(arylhydrazones) of isoascorbic acid were prepared; the latter are present in two forms that afford the same pyrazoledione. Acetylation, benzoylation, and periodate oxidation of these pyrazolediones were studied, and some condensation products from the pyrazole aldehyde were prepared. Some of the i.r. and mass-spectral data were discussed.     

Facile synthesis and rearrangement of L-threo-2,3-hexodiulosono-1,4-lactone 2-(2-arylhydrazones)

Controlled reaction of L-threo-2,3-hexodiulosono-1,4-lactone with substituted phenylhydrazines gave the 2-(monoarylhydrazones) (2), which underwent dehydrative acetylation to 4-(2-acetoxyethylidene)-4-hydroxy-2,3-dioxohutyro-1,4-lactone 2-(2-arylhydrazones) (3). The latter reacted with methylhydrazine to give 1-methyl-3-(1-methylpyrazolin-3-yl)-4,5-pyrazoledione 4-(2-arylhydrazones) (4). Reaction of the monoarythydrazones (2) with phenylhydrazine gave the mixed bishydrazones (5), which were rearranged by alkali and acidification to the pyrazolediones (6). Compounds 6 gave triacetyl (7) and tribenzoyl derivatives (8), and, on periodite oxidation, the aldehydes (9), which afforded the monohydrazones (10). The i.r.. n.m.r.. and mass-spectral data of some of the compounds were investigated.     

Reactions of the 3-oxime 2-phenylhydrazone and mixed bishydrazones of dehydro-L-ascorbic acid: Conversion into substituted triazoles and pyrazolinediones

L-threo-2,3-Hexodiulosono-1,4-lactone 2-phenylhydrazone(1) reacted with hydroxylamine to give the 3-oxime 2-phenylhydrazone(2). On boiling with acetic anhydride,2 was dehydrated to 4-[L-threo-2,3-diacetoxy-(1-hydroxypropyl)]-2-phenyl-1,2,3-triazole-5-car?ylic acid lactone(3), which was converted into 2-phenyl-4-(L-threo-1,2,3-trihydroxypropyl)-1,2,3-triazole-5-car?amide(4) with liquid ammonia. The structure of compound4 was confirmed by acetylation to 2-phenyl-4-(L-threo-1,2,3-triacetoxypropyl)-1,2,3-triazole-5-car?amide(5), and by periodate oxidation followed by reduction, to give 4-(hydroxymethyl)-2-phenyl-1,2,3-triazole-5-car?amide(6). Treatment of compound1 with aryl- or aroyl-hydrazines afforded mixed bishydrazones(7–14), which were acetylated to15–21, and treated with hydrazine to give pyrazolinediones22 and23     

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

-threo-2,3-Hexodiulosono-1,4-lactone 2-(arylhydrazones) (2) were prepared by condensation of dehydro- -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- -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-( -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-( -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- -threo-2,3-hexodiulosono-1,4-lactone 2-(arylhydrazones); these were converted into 4-(2-O-acetyl-3-bromo-3-deoxy- -threo-glycerol-l-yl)-2-aryl-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones on treatment with acetic anhydride-pyridine.     

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

d-erythro-2,3-Hexodiulosono-1,4-lactone 2-arylhydrazones (2) were prepared by condensation of dehydro-d-arabino-ascorbic acid with the desired arylhydrazine. 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-d-erythro-glycerol-1-yl)-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone (5), whereas the unacetylated triazole derivatives were obtained upon reaction of 3 with bromine in water. On treatment of 5 with hydrazine hydrate, 2-aryl-4-(d-erythro-glycerol-1-yl)-1,2,3-triazole-5-carboxylic acid 5-hydrazides (6) were obtained. Acetylation of 6 gave the hexaacetyl derivatives. Similarly, treatment of 5 with liquid ammonia gave the triazolecarboxamides (12). Vigorous acetylation of 12 with boiling acetic anhydride gave tetraacetates, whereas acetylation with acetic anhydride-pyridine gave triacetates. Periodate oxidation of 6 gave the 2-aryl-4-formyl-1,2,3-triazole-5-carboxylic acid 5-hydrazides (8), and, on reduction, 8 gave the 2-aryl-4-(hydroxymethyl)-1,2,3-triazole-5-carboxylic acid 5-hydrazides, characterized as acetates. Similarly, periodate oxidation of 12 gave the triazolealdehyde (15), and reduction of 15 gave the hydroxymethyl derivatives (16). Acetylation of 16 gave the mono- and di-acetates, and, on reaction with o-phenylenediamine, 15 afforded the triazoleimidazole. Controlled reaction of 3 with sodium hydroxide, followed by neutralization, gave 3-(d-erythro-glycerol-1-yl)-4,5-isoxazolinedione 4-arylhydrazones. Reaction of 3 with HBr-HOAc gave 5-O-acetyl-6-bromo-6-deoxy-d-erythro-2,3-hexodiulosono-1,4-lactone 2-arylhydrazone 3-oximes (21). Compounds 21 were converted into 4-(2-O-acetyl-3-bromo-3-deoxy-d-erythro-glycerol-1-yl)-2-aryl-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone on treatment with acetic anhydride.     

β-elimination in aldonolactones. Synthesis of 2-deoxy-D-lyxo-hexose and 2-deoxy-D-arabino-hexose

Benzoylation of D-glycero-L-manno-heptono-1,4-lactone (1) with benzoyl chloride and pyridine for 2 h afforded crystalline penta-O-benzoyl-D-glycero-L-manno-heptono-1,4-lactone (2), but a large excess of reagent during 8 h also led to 2,5,6,7-tetra-O- benzoyl-3-deoxy-D-lyxo-hept-2-enono-1,4-lactone (3). Catalytic hydrogenation of 3 was stereoselective and gave 2,5,6,7-tetra-O-benzoyl-3-deoxy-D-galacto-heptono-1,4-lactone (4). Debenzoylation of 4 followed by oxidative decarboxylation with ceric sulfate in aqueous sulfuric acid gave 2-deoxy-D-lyxo-hexose (5). Application of the same reaction to 3-deoxy-D-gluco-heptono-1,4-lactone afforded 2-deoxy-D-arabino-hexose (6).     

The inhibitory activities of 2-acetamido-2,3-dideoxy-D-hex-2-enonolactones on 2-acetamido-2-deoxy-beta-D-glucosidase.

Treatment of 2-acetamido-2-deoxy-D-mannono-1,4-lactone with dicyclohexylamine in ethanolic solution afforded an unsaturated 1,4-lactone, 2-acetamido-2,3-dideoxy-D-erythro-hex-2-enono-1,4-lactone (1), in good yield. 2-Acetamido-2,3-dideoxy-D-threo-hex-2-enono-1,4-lactone (2) was similarly prepared from 2-acetamido-2-deoxy-D-galactono-1,4-lactone. An unsaturated 1,5-lactone, 2-acetamido-2,3-dideoxy-D-threo-hex-2-enono-1,5-lactone (4), was obtained through the oxidation of 2-acetamido-2-doexy-4,6-0-isopropylidene-D-galactopyranose with silver carbonate on Celite, followed by mild hydrolysis. The inhibitory activity of four isomeric 2-acetamido-2,3-dideoxy-D-hex-2-enonolactones [1, 2, 4, and 2-acetamido-2,3-dideoxy-D-erythro-hex-2-enono-1,5-lactone (3)] was assayed against 2-acetamido-2-deoxy-beta-D-glucosidase from bull epididymis. Only the erythro lactones 1 and 3 are weak competitive inhibitors, whereas the threo lactones 2 and 4 are practically inactive. The 1,4-lactone 1 inhibited 2-acetamido-2-deoxy-beta-D-glucosidase more strongly than the 1,5-lactone 3. The lactones 1-4 were found to be quite stable in aqueous solution or under inhibitory-assay conditions. In addition, two 2-acetamido-2-deoxy-D-glycals, 2-acetamido-1,5-anhydrohex-1-enitol (7) were tested; both are 10 times as active as 1.     

3-desoxyhex-2-enono-1,4-lactone aus D-hexofuran(osid)- urono-6,3-lactonen

The yield of 2-O-benzyl-3-deoxy-L-threo-hex-2-enono-1,4-lactone by reaction of 5-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranurono-6,3-lactone with sodium borohydride was improved by variation of the aprotic dipolar solvent and temperature. The general validity of this elimination—reduction reaction was ascertained by conversion of eleven other D-hexofuran(osid)urono-6,3-lactones into various 3-deoxy-hex-2-enono-1,4-lactones by treatment with sodium borohydride in hexamethyl phosphoric triamide.     

Some reactions of a furanoid 2-aminoglycal derivative

Some reactions, catalyzed by p-toluenesulfonic acid, of 2-acetamido-1,4-anhydro-2-deoxy-5,6-O-isopropylidene-d-arabino-hex-1-enitol (1), a furanoid 2-aminoglycal derivative, were examined. Reaction with methyl and with benzyl alcohol gave the corresponding furanoid 2,3-unsaturated glycosides (2 and3) in good yield. Similar reaction with water, followed by acetylation, gave 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-d-ribo-hex-2-enopyranose, which was hydrogenated to 2-acetamido-1,4,6-tri-O-acetyl-2,3-dideoxy-d-ribo-hexopyranose (an N-acetyllividosamine derivative) and its arabino analog. Addition of a catalytic amount of p-toluenesulfonic acid to a solution of 1 in dry 1,4-dioxane afforded furanoid, (1→3)-disaccharides in high yield. Tosylation of 1 to yield a furan derivative was, however, unsuccessful. Hydrogenation of methyl 2-acetamido-2,3-dideoxy-5,6-O-isopropylidene-d-erythro-hex-2-enofuranoside (2) was examined by use of palladium-on-carbon, as well as platinum oxide, as the catalyst     

Studies on the koenigs-knorr reaction : Part IV: The effect of participating groups on the stereochemistry of disaccharide formation

Partial benzylation of methyl 2-O-benzyl-α-L-fucopyranoside afforded a mixture of methyl 2,3-, and 2,4-di-O-benzyl-α-L-fucopyranoside which were separated by means of their monoacetates. Partial benzylation of methyl α-L-fucopyranoside gave the 2,4-, and 3,4-dibenzyl ethers in the ratio of 3:2, and no 2,3-isomer could be detected in the reaction mixture. The structures of the three dibenzyl ethers were established: (a) by analysis of the n.m.r. spectra of their acetates, and (b) by methylation, removal of benzyl groups by hydrogenolysis, and characterization of the methyl ethers of the methyl glycosides. Acid hydrolysis of these compounds gave the monomethyl ethers of L-fucose, two of which were identical with known compounds, whereas the third, 4-O-methyl-L-fucose, was a new compound. Selective p-nitrobenzoylation of 2,3-, 2,4-, and 3,4-di-O-benzyl-L-fucose, followed by acetylation and treatment with hydrogen bromide in dichloromethane, gave the three possible mono-O-acetyl-di-O-benzyl-α-L-fucopyranosyl bromides, which were condensed with benzyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-α-D-glucopyranoside. The disaccharide derived from the 2-O-acetyl substituted bromide was enriched in β-L-fucopyranoside, whereas the other two bromides gave mainly the α-L-linked anomer. The α-directing influence of the 3- and 4-O-acetyl substituents is not less than the β-directing influence of the 2-O-acetyl group in similar bromides; participation of acyl groups and electronic-steric influences are discussed as possible explanations for the steric course of the reaction.     

The preparation of some bromodeoxy- and dibromodideoxy-pentonolactones

Treatment of ammonium d-xylonate with hydrogen bromide in acetic acid yields 2,5-dibromo-2,5-dideoxy-d-lyxono-1,4-lactone (2a), whereas similar treatment of potassium d-arabinonate gives 5-bromo-5-deoxy-d-arabinono-1,4-lactone (8a) as the main product. Two isomeric 2,5-dibromo-2,5-dideoxy-1,4-lactones are also formed in minor amounts. Selective hydrogenolysis of 2a affords 5-bromo-2,5-dideoxy-d-threo-pentono-1,4-lactone, while prolonged treatment results in the formation of 3-hydroxypentanoic acid. Similarly, hydrogenolysis of 8a produces a 2,3-dihydroxypentanoic acid together with smaller amounts of 5-deoxy-d-arabinono-1,4-lactone; the latter also results from hydrogenolysis of 5-deoxy-5-iodo-d-arabinono-1,4-lactone with Raney nickel.     

Polydeoxyaminohexopyranosylnucleosides. Synthesis of 1-(2,3,4-Trideoxy-3-nitro-β-D-erythro- and threo-hexopyranosyl)-uracils from Uridine

Abstract

The first synthesis of nitro-multideoxy-sugar containing nucleosides was achieved. 1-(4,6-O-Benzylidene-3-deoxy-3-nitro-β-D-glucopyranosyl)uracil (3) was converted in 75% yield into 1-(4,6-O-benzylidene-2,3-dideoxy-3-nitro-arabinohexopyranosyl)uracil (7) by acetylation followed by NaBH₄ reduction in methanol. De-O-benzylidenation with CF₃CO₂H afforded crystalline 1-(2,3-dideoxy-3-nitro-β-D-arabinohexopyranosyl)uracil (S) was obtained in 87% yield. Raney Ni reduction of 8 afforded the corresponding 3′-amino-nucleoside 9. Acetylation of 8 followed by NaBH₄ treatment afforded an 8:1 mixture from which 1-(2,3,4-trideoxy-3-nitro-β-D-threohexopyranosyl)-uracil (14) was obtained in pure crystalline form. After Raney Ni reduction of the mixture, 1-(3-amino-2,3,4-trideoxy-β-d-threo-hexopyranosyl)uracil (16) and its erythro epimer 21 were isolated. 1-(4,6-O-Benzylidene-2,3-dideoxy-3-nitro-β-d-lyxohexopyranosyl)uracil (24) was prepared in 72% yield from 1-(4,6-O-benzylidene-3-deoxy-3-nitro-β-d-galactopyranosyl)uracil (4) by acetylation and subsequent reduction with NaBH₄. De-O-benzylid-enation of 23 afforded 1-(2,3,4-trideoxy-3-nitro-β-d-lyxohexopyranosyl)uracil (25) in 83% yield. Schmidt-Rutz reaction of 25 followed by NaBH₄ reduction afforded a mixture of threo and elythro isomers of 2′,3′,4′-trideoxy-3′-nitro-hexopyranosyluracil, from which pure 16 and 21 were obtained.

     

Synthesis of 2,4-diacetamido-2,4,6-trideoxy-D-Galactose

Treatment of benzyl 2-acetamido-3-O-benzyl-2,6-dideoxy-4-O-(methylsulfonyl)-α-D-glucopyranoside (1) with sodium azide in hexamethylphosphoric triamide gave the 4-azido-α-D-galacto derivative (2), which was converted into benzyl 2,4-di-acetamido-3-O-benzyl-2,3,6-trideoxy-α-D-galactopyranoside (3) by hydrogenation and subsequent acetylation. Hydrogenolysis of 3 at atmospheric pressure afforded benzyl 2,4-diacetamido-2,4,6-tridcoxy-α-D-galactopyranoside (4), which was acetylated to give the 3-O-acetyl derivative (5). The n.m.r. spectrum of 5 was in agreement with the assigned structure and different from that of benzyl 2,4-di-acetamido-3-O-acetyl-α-D-glucopyranoside (9), which was prepared from the known benzyl 2,4-diacetamido-3-O-benzyl-2,4,6-trideoxy-α-D-glucopyranoside. Catalytic hydrogenolysis of 4 gave 2,4-diacetamido-2,4,6-trideoxy-D-galactose (6).