Synthesis of L-daunosamine derivatives on the basis of the asymmetric dihydroxylation of 3-((E)-1-propenyl)-4,5-dihydroisoxazole

Abstract

Methyl L-N,O-diacetyldaunosaminide was prepared from 3-nitro-4,5-dihydroisoxazole in 8.5% overall yield. A key step in the synthesis involved the AD reaction of (E)-3-(1-propenyl)-4,5-dihydroisoxazole (2b), affording the corresponding diol in 76% yield (92% ee). A second key step involved reductive cleavage of the dihydroisoxazole 4a and subsequent N-acetylation to afford separable diastereomeric γ-(acetylamino)alcohols 7a and 8a in 62% yield (72:28, 7a/8a). Swern oxidation of 7a and subsequent methanolysis followed by acetylation provided methyl L-N,O-diacetyldaunosaminide as an anomeric mixture. The AD reactions of chiral alkenyl dihydroisoxazole 16 with (DHQ)2-PHAL and (DHQD)2-PHAL afforded diastereomeric diol products, isolated as the acetates 18 and 19 (98:2 and 5:95 ratios, respectively, depending on the chiral auxiliary).