Synthesis of 3-acetamido-2,3,6-trideoxy-D-lyxo-hexose (N-acetyl-D-daunosamine) and its D-arabino isomer

Abstract
Two syntheses of 3-acetamido-2,3,6-trideoxy-D-lyxo-hexose (N-acetyl-D-daunosamine, 14) are described. The first one starts from methyl 3-acetamido-2,3-dideoxy-β-D-arabino-hexopyranoside (1) which is converted via its 6-O-tosylate (2) and 4-O-acetyl 6-O-tosylate (3) into methyl 3-acetamido-4-O-acetyl-2,3,6-trideoxy-6-iodo-β-D-arabino-hexopyranoside (5). Under certain conditions the last step involves a partial anomerization giving the α-anomer (6) as an additional product. Both 5 and 6 may be reductively dehalogenated to the corresponding 4-O-acetates having a 6-deoxy function (7 and 8). Preferably, 5 is reduced and simultaneously de-O-acetylated to methyl 3-acetamido-2,3,6-trideoxy-β-D-arabino-hexopyranoside (9). This glycoside is converted into its β-D-lyxo isomer (13) by solvolysis of the 4-O-mesylate (12). Hydrolyses of 9 give 3-acetamido-2,3,6-trideoxy-D-arabino-hexose (10) and the corresponding amino sugar hydrochloride (11), while hydrolyses of 13 give N-acetyl-D-daunosamine (14) and a syrupy amino sugar hydrochloride. The second synthesis of 14 departs from the D-lyxo isomer (15) of 1 and proceeds in a similar sequence via the 4-O-acetylated derivatives with 6-O-tosyl (16), 6-deoxy-6-iodo (17), and 6-deoxy (18) functions, the two last-mentioned compounds being α-glycosides due to anomerization in the step 16 → 17.