Deoxy‐nitrosugars 15th communication Synthesis of <i>N</i>‐acetylneuraminic acid and <i>N</i>‐acetyl‐4‐epineuraminic Acid

Abstract

Abstract A synthesis of N ‐acetylneuraminic acid ( 1 ) and of N ‐acetyl‐4‐epineuraminic acid ( 2 , R = H) from 2‐acetamido‐4,6‐ O ‐benzylidene‐1,2‐dideoxy‐1‐nitro‐ D ‐mannopyranose ( 3 ) and 2‐acetamido‐1,2‐dideoxy‐4,6‐ O ‐isopropylidene‐1‐nitro‐ D ‐mannopyranose ( 4 ), respectively, is described. Michael addition of 3 and 4 to tert ‐butyl 2‐(bromomethyl)prop‐2‐enoate ( 5 ) and subsequent hydrolytic removal of the NO 2 group gave the 4‐nonulosonate tautomers 6 / 7 and 8 / 9 , respectively ( Scheme ). Stereoselective reduction of 6 / 7 and 8 / 9 with NaBH 4 /AcOH in dioxane/H 2 O yielded 12/13 (94:6) and 14/15 (92:8), respectively. Reduction of 6 / 7 and 8 / 9 in the absence of AcOH or in EtOH gave 12 / 13 (15:85) and 14 / 15 (15:85), respectively. Ozonolysis of 12 and 13 followed by hydrolysis gave tert ‐butyl neuraminate 22 and tert ‐butyl 4‐epineuraminate 24 , respectively. Ozonolysis of 14 / 15 , separation of the products 20 and 21 , and hydrolytic removal of the isopropylidene groups gave 22 and 24 , respectively. The tert ‐butyl ester 22 was saponified to give 1 , which was further characterized as the methyl ester 23 . Saponification of 24 gave the crude 4‐epimer of 1 , which was converted into the stable Na salt 2 and also into the methyl ester 25 .