Synthesis of 4-deoxydaunosamine and 4-deoxyristosamine

Abstract

Treatment of methyl 3,6-dideoxy-2,4-di-O-methylsulfonyl-3-nitro-α-L-glucopyranoside (2) with sodium acetate and acetic acid in acetone gave methyl 4-O-acetyl-2,3,6-trideoxy-3-nitro-α-L-erythro-hex-2-enopyranoside (3) as a kinetic product, and the 2-O-acetyl-3,4,6-trideoxy-3-nitro-α-L-threo-hex-3-eno isomer 4 as the thermodynamically preferred product. Treatment of 2 or 4 with sodium borohydride produced a separable mixture of methyl 2,3,4,6-tetradeoxy-3-nitro-α-L-threo-hexopyranoside (5) and its α-L-erythro epimer (6), the latter being convertible into the former by base-catalyzed epimerization. Acid hydrolysis of 5 and 6 afforded the corresponding free nitro sugars 7 and 8. Catalytic hydrogenation of 5 led to the corresponding amino glycoside, isolated as the acetate 9 or hydrochloride 10; similarly, 6 gave the epimeric amine which was isolated as its acetate 14 or picrate 15. N-Trifluoroacetylation of 9 provided the N-trifluoroacetyl glycoside 12 which was hydrolyzed to give a 49% yield (overall from 2) of 2,3,4,6-tetradeoxy-3-trifluoroacetamido-L-threo-hexose (4-deoxy-N-trifluoroacetyldaunosamine, 13). Analogously, 14 afforded the epimeric N-trifluoroacetyl glycoside 17 which was hydrolyzed to give a 28% overall yield of 2,3,4,6-tetradeoxy-3-trifluoroacetamido-L-erythro-hexose (4-deoxy-N-trifluoroacetylristosamine, 18).