STUDIES ON THE SYNTHESIS OF SIALOSIDES AND SIALIC-ACID ANALOGS .2. A SIMPLE PROCEDURE FOR THE SYNTHESIS OF THE METHYL AND BENZYL GLYCOSIDES OF NEU5AC AND 4-EPI-NEU5AC - CONVERSION OF THE BENZYL AND METHYL GLYCOSIDES OF NEU5AC INTO N-TRIFLUOROACETYLNEURAMINIC ACID BENZYL GLYCOSIDES

From the reaction products of the Kuhn-Bashang synthesis of Neu5Ac, 5-acetamido-3,5-dideoxy-alpha- and -beta-D-glycero-D-talo-2-nonulopyranosonic acid (4-epi-Neu5Ac) were isolated as the acetylated methyl esters (1 and 2). Treatment of methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-D-galacto-2-nonulopyranosyl bromide)onate (5) with an excess of methanol gave a high yield of a 9:1 alpha,beta-mixture of the methyl glycosides (13 and 14). Likewise, with benzyl alcohol, 5 gave a 63:32 alpha,beta-mixture of the benzyl glycosides (17 and 18). Treatment of methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-beta-D-glycero-D-talo-2-nonulopyranosyl bromide)onate (7) with an excess of benzyl alcohol gave a 3:1 alpha,beta-mixture of the benzyl glycosides (21 and 22) together with methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-talo-non-2-enonate (9). Condensation of bromide 7 in chloroform with benzyl alcohol in the presence of silver carbonate afforded a 7:1 alpha,beta-mixture of benzyl glycosides together with 9. The benzyl glycosides 17 and 18 were converted into their respective N-trifluoroacetyl derivatives 27 and 28 by saponification and then N-trifluoroacetylation. Methanolysis of Neu5Ac followed by N-trifluoroacetylation and O-acetylation afforded methyl (methyl 4,7,8,9-tetra-O-acetyl-3,5-dideoxy-5-trifluoroacetamido-beta-D-glycero-D-galacto-2-nonulopyranosid)onate (30), which was converted into the benzyl glycosides (32 and 33) via the 2-bromide (31). A simplified preparation of the protected 2-halogeno derivatives of Neu5Ac and 4-epi-Neu5Ac is described. The conversion of neuraminic acid methyl glycoside into the corresponding 2-bromide derivative by the action of hydrogen bromide is demonstrated.