Modifications at C-3 and C-4 of 2-amino-2-deoxy-D-glucose

Modifications at C-3 and C-4 of 2-amino-2-deoxy-D-glucose have been developed. A 3,4-double bond was introduced into benzyl 2-acetamido-2-deoxy-3,4-di-O-methylsulfonyl-alpha-D-glucopyranoside by treatment with NaI and Zn. Epoxidation of the double bond with m-chloroperoxybenzoic acid gave an exo-epoxide exclusively. The stereochemistry of the epoxidation product has been confirmed by an alternative synthesis. An analysis of the 1H-n.m.r. spectra indicates that both the 3,4-unsaturated derivatives and the epoxide exist in the OH1 (D) conformation. Nucleophilic reagents (F-, I-) opened the 3,4-epoxide to give 4-substituted derivatives having the D-gulo configuration. Thus, 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-4-iodo-alpha-D-gulopyranose and 2-acetamido-1,3,6-tri-O-acetyl-3,4-dideoxy-4-fluoro-alpha-D-gulopyranose have been synthesized. Reduction of the double bond in the key intermediate and deprotection gave 2-acetamido-2,3,4-trideoxy-D-glucopyranose. Some of the derivatives were active as inhibitors of growth of mouse, mammary adenocarcinoma cells in culture.