Synthesis of 6-azido- and 6-amino-2,3,6-trideoxy- d- erythro-hexose

Abstract

The synthesis of 6-azido- and 6-amino-2,3,6-trideoxy- d- erythro-hexose ( 19 and 22) and several of their derivatives is described. Hydrogenation and hydrogenolysis of methyl 4,6- O-benzylidene-2,3-dideoxy-α- d- erythro-hex-2-enopyranoside ( 1) gave methyl 2,3-dideoxy-α- d- erythro-hexopyranoside ( 3), which was transformed into methyl 6-azido-2,3,6-trideoxy-α- d- erythro-hexopyranoside ( 9) via the 6-tosylate or the 6- O-tris(dimethylamino)phosphonium bromide derivative. The 4-acetate ( 8) or 9 was also prepared from methyl 4- O-acetyl-2,3-dideoxy-6- O-toluene- p-sulphonyl-α- d- erythro-hexopyranoside ( 7). Hydrogenation or 8 in methanol-acetic anhydride gave the diacetate 12. Reduction of 8 in methanol gave a mixture (1:2) of unstable 4- O-acetyl-6-amino-2,3,6-trideoxy-α- d- erythro-hexopyranoside ( 10) and methyl 6-acetamido-2,3,6-trideoxy-α- d- erythro-hexopyranoside. Reduction of 9 afforded methyl 6-amino-2,3,6-trideoxy-α- d- erythro-hexopyranoside ( 13). Transformation of 1, via the 6-bromo-4- O-benzoyl derivative 15, into methyl 6-azido-4- O-benzoyl-2,3,6-trideoxy-α- d- erythro-hexopyranoside ( 16), followed by O-debenzoylation, afforded 9. Hydrogenation of 16 in the presence of acetic anhydride gave methyl 6-acetamido-4- O-benzoyl-2,3,6-trideoxy-α- d- erythro-hexopyranoside ( 17), which yielded 11 on O-debenzoylation. Acid hydrolyses of 3 and 9 liberated the corresponding free sugars 18 and 19. Hydrolysis of 11 gave 6-acetamido-2,3,6-trideoxy- d- erythro-hexopyranose ( 20) and minor amounts of the 1,6-anhydro derivative 21. Acetolysis of 11 afforded 6-acetamido-4- O-acetyl-1,6-anhydro-2,3,6-trideoxy-β- d- erythro-hexopyranose ( 22), the O-deacetylation of which yielded a mixture of the bicyclic compound 21 (major product) and 20.