Synthesis of anomeric sulfonamides and their behaviour under radical-mediated bromination conditions.

ABSTRACT

O-Peracetylated methyl 3-(d-glycopyranosylthio)propanoates of beta-d-gluco, and alpha- and beta-d-galacto configurations were oxidized to the corresponding S,S-dioxides (sulfones) by Oxone or MCPBA. Oxidation of the beta-D-gluco derivative with H(2)O(2)/Na(2)WO(4) gave the corresponding S-oxide (sulfoxide). DBU-induced elimination of methyl acrylate from the beta-D-gluco and beta-D-galacto configured S,S-dioxides (sulfones) gave O-peracetylated beta-D-glycopyranosyl-1-C-sulfinates which, on treatment with H(2)NOSO(3)H, furnished the corresponding beta-D-glycopyranosyl-1-C-sulfonamides. Radical-mediated bromination of the protected methyl 3-(beta-D-glycopyranosylthio)propanoate S,S-dioxides gave mixtures of 1-C- and 5-C-bromoglycosyl compounds. Similar brominations of the O-peracetylated beta-D-glycopyranosyl-1-C-sulfonamides resulted in the formation of alpha-D-glycopyranosyl bromides and 1-C- and 5-C-bromoglycosyl sulfonamides. A rationale for these observations was proposed. Methyl 3-(beta-D-glucopyranosylthio)propanoate, its S,S-dioxide, and beta-D-glucopyranosyl-1-C-sulfonamide proved inefficient when tested as inhibitors of rabbit muscle glycogen phosphorylase b.