Synthesis and reactions of α- and β- d-glucopyranosyluronic esters of amino acids

Abstract

The synthesis of the fully benzylated α- and β- d-glucopyranosyluronic esters of 1-benzyl N-benzyloxycarbonyl- l-aspartic and -glutamic acids and N-( tert-butoxycarbonyl)- l-phenylalanine, followed by hydrogenolysis, afforded the respective anomers of the 1- O-acyl- d-glucopyranuronic acids 2, 7, and 12. Esterification of both anomers of the N-acetylated derivatives of 2 and 7 by diazomethane was accompanied by glycosyl-bond cleavage, and, in the case of the α anomers, with concomitant 1→2 acyl migration to give, after O-acetylation, the 2- O-acyl O-acetyl methyl ester derivatives 5 and 10, respectively. Similarly, 12α yielded methyl 1,3,4-tri- O-acetyl-2- O-[ N-( tert-butoxycarbonyl)- l-phenylalanyl]- d-glucopyranuronate and an analogue having a furanurono-6,3-lactone structure. Esterification of the C-5 carboxyl group, in 1- O-acyl-α- d-glucopyranuronic acids by methanol in the presence of the BF 3 − -MeOH reagent (1–1.5 equiv.) proceeded without acyl migration. By using this procedure, followed by acetylation, the N-acetylated derivative of 7α afforded methyl 2,3,4-tri- O-acetyl-1- O-(1-methyl N-acetyl- l-glutam-5-oyl)-α- d-glucopyranuronate, and 12α gave methyl 2,3,4-tri- O-acetyl-1- O-( N-acetyl- l-phenylalanyl)-α- d-glucopyranuronate; the formation of the latter involved cleavage of the tert-butoxycarbonyl group by BF 3, followed by N-acetylation in the next step.