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Oxidation of 5-acetamido-4,8-anhydro-1,2,3,5-tetradeoxy-D-glycero-D-ido-non-1-enitol [3-C-(2-amino-2-deoxy-beta-D-glucopyranosyl)-1-propene] was studied to search for preparative routes to aminodeoxy didehydro nonulosonic acid derivatives. Since only moderate chiral induction was observed with osmium tetroxide dihydroxylation as well as with peracid epoxidation, the catalytic asymmetric dihydroxylation conditions were applied to give the stereocontrolled formation of 1,2-propanediol derivatives. The structures of these diastereoisomeric 1,2-propanediol derivatives were determined by X-ray crystallographic analyses. The formation of diastereoisomeric 1,2-propanediols also varied with the nature of 2-substituent on the aminodoexy glycosyl moiety. Thus 5-acetamido-4,8-anhydro-3,5-dideoxy-D-erythro-L-ido-nonitol [(2S)-3-C-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-1,2-propanediol] was obtained predominantly up to 70% from 3-C-(2-acetamido-2-deoxyglycosyl)-1-propene by the use of ADmixbeta reagent. The (2S)-propanediol derivative was transformed in a five-step reaction sequence to 2,3-didehydro-2,7-dideoxy-N-acetylneuraminic acid., (Copyright 2002 Elsevier Science Ltd.)

The aminocyclitol antibiotic neamine has been modified by changing the configuration of one or two hydroxyl groups of the aminocyclitol moiety to elucidate the relationship between configuration and antimicrobial activity. 5-Epi-, 6-epi-, and 5,6-diepineamine have been prepared and their antimicrobial activity has been determined against several micro-organisms.

Pseudo-alpha- and pseudo-beta-DL-glucose, the isomers of 5-hydroxymethyl-1,2,3,4-cyclohexanetetrol with alpha-gluco and beta-gluco configurations, were used as synthetic analogs of glucose anomers to study the mechanism of glucose-stimulated insulin release by pancreatic islets. Neither isomer was phosphorylated by liver glucokinase nor stimulated insulin release from islets. Incubation of islets with pseudo-alpha-DL-glucose resulted in a considerable accumulation of the glucose analog, probably the D form, in islets. The alpha-isomer, but not the beta-isomer, inhibited both glucose-stimulated insulin release (44% inhibition at 20 mM) and islet glucokinase activity (36% inhibition at 20 mM) in a concentration-dependent manner and to a comparable degree. These results strongly suggest that the inhibition of glucose-stimulated insulin release by pseudo-alpha-DL-glucose is due to the inhibition of islet glucokinase by the glucose analog, providing additional evidence for the essential role of islet glucokinase in glucose-stimulated insulin release.

Chlorination of antibiotic fortimicin A with triphenylphosphine and carbon tetrachloride has been attempted, and 2-chloro-, 2,5-dichloro-, and 2-chloro-4-ene derivatives have been obtained. Successive dehalogenation of the chlorinated fortimicins A with tributylstannane gave the corresponding deoxyfortimicins A. Among five deoxyfortimicins A, 2-deoxyfortimicin A exhibits improved antimicrobial activity, compared to the parent fortimicin A.

N-(2-Chloroethyl)-N-nitrosocarbamoyl derivatives of glycosylamines have been prepared. Six N-(2-chloroethyl)-N-nitrosoureas, including three disaccharide derivatives, were submitted to a determination of antitumor activity. All the compounds tested exhibited strong antitumor activity against leukemia L1210 in mice.

Fourteen (2-chloroethyl)nitrosourea congeners of L-amino acid amides have been synthesized as potential antineoplastic agents. Almost all the congeners tested were found to be highly active against experimental leukemia L1210 in mice. The chemical decomposition rates of the congeners were measured in a buffered solution (pH 7.4) at 37 degrees C. Acute toxicities of some of the congeners were determined for mice. The congener of sarcosinamide shows the longest half-life (T0.5 = 329.7 min) and the lowest toxicity, LD50 = 392.0 mg/kg (ip) and 426.6 mg/kg (iv), in this series.

The aminocyclitol antibiotic neamine has been chemically modified at the hydroxyl group on C-6 of the 2-deoxystrepatamine moiety. The partially acetylated neamine derivatives, 6,3,4-tri-O-acetyl- (3) and 5,3-57,4-tri-O-acetyl-1,3,2,6-tetra-N-(ethoxycarbonyl)neamine (4), were prepared by random hydrolysis of the 5,6-O-ethoxyethylidene derivative (2), followed by chromatographic purification. Condensation of 4 and 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride led to 6-O-(beta-D-ribonfuranosyl)neamine (7). Analogous condensation of 4 with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide or 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide afforded the corresponding 6-O-(D-hexopyranosyl)neamines.