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

Abstract

From the reaction products of the Kuhn-Bashang synthesis of Neu5Ac, 5-acetamido-3,5-dideoxy- α-and - β- 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 α,β-mixture of the methyl glycosides ( 13 and 14). Likewise, with benzyl alcohol, 5 gave a 63:32 α,β-mixture of the benzyl glycosides ( 17 and 18). Treatment of methyl (5-acetamido-4,7,8,9-tetra- O-acetyl-3,5-dideoxy- β- d- glycero-pd- talo-2-nonulopyranosyl bromide)onate ( 7) with an excess of benzyl alcohol gave a 3:1 α,β-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 α,β-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- β- d- glycero- d- galacto-2-nonulopyrano-sid)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.