Syntheses of sialic acid analogues with acylamino groups at C-4 (N-acyl regioisomers of sialic acids)

Methyl 5,7,8,9-tetra-O-acetyl-4-acylamino-2,6-anhydro-3,4-dideoxy-d-glycero-d-galacto- and d-talo-non-2-enonates were synthesized from the reaction of the peracetate of Kdn methyl ester with several nitriles in the presence of a Lewis acid. Treatment of these 2,4-dideoxy-4-acylamino-Kdn methyl esters with N-bromosuccinimide in methanol gave methyl (methyl 5,7,8,9-tetra-O-acetyl-4-acylamino-3-bromo-3,4-dideoxy-d-erythro-α-l-manno-non-2-ulopyranosid)onates (16, 18, and 20) and oxazine-type derivatives, 2-alkyl-(methyl 5,7,8,9-tetra-O-acetyl-3-bromo-3,4-dideoxy-d-erythro-α-l-manno-non-2-ulopyranosonate)-5,6-dihydro-4H-1.3-oxazine (29, 30, and 31). Debromination of 16, 18, and 20 with Bu3SnH/AIBN in toluene gave methyl (methyl 5,7,8,9-tetra-O-acetyl-4-acylamino-3,4-dideoxy-β-d-glycero-d-galacto-nonulopyranosid)onate (23, 24, and 25), whereas hydrolysis with HOAc and subsequent debromination with Bu3SnH/AIBN in toluene of 32 and 33 gave methyl 5,7,8,9-tetra-O-acetyl-4-acylamino-3,4-dideoxy-β-d-glycero-d-talo-2-nonulopyranosonate (35 and 36) in the final step of the synthesis.