It is well known that naturally occurring sialo compounds such as glycoproteins and glycolipids in cell membranes, which play important roles in biological systems'-', contain sialic acids in a-glycosidic linkage. Therefore, a facile, a-selective synthesis of sialic-acid glycosides is very important.
Recently, new efforts 69 have been made towards the synthesis of a-glycosides of N-acetylneuraminic acid (NeuSAc), but the procedure still remains to be improved with respect to yields, regio-and stereo-selectivity, and potential for scale-up.
We have developed'@'3 a procedure for regio-and a-stereo-selective glycosylation with sialosyl groups involving the reaction of the methyl a-thioglycosides of sialic acids as the glycosyl donors, suitably protected acceptors, and dimethyl(methylthio)sulfoniurn triflate14 (DMTST) in acetonitrile under kinetically controlled conditions. In this manner, we have synthesized'@'2,'5*'6 a variety of gangliosides and their analogs. However, the preparation"."
of the important glycosyl donor, namely the methyl a-thioglycoside of NeuSAc, requires several steps from NeuSAc, and seems to be unsuitable for large-scale synthesis. For the efficient synthesis of various types of sialo-oligosaccharides and their analogs, required for studies of the functions of sialoglycoconjugates at the molecular level, it is critically important to circumvent this difficulty. We report here a facile, large-scale preparation of an alternative glycosyl donor, a 1: 1 anomeric mixture of the methyl thioglycosides of NeuSAc, and its usefuesness for the a-stereoselective synthesis of sialoglycosides.
Treatment of N-acetylneuraminic acid with Amberlite IR-120 (H+) resin in methanol and subsequent acetylation with acetic anhydride in pyridine" gave methyl 5-acetamido-2,4,7,8,9-penta-O-acetyl-3,5-dideoxy-o-glycero-D-galacto-2-nonulopyranosonate (1) in almost quantitative yield. The anomeric ratio (a:/?) was estimated as 3:8 from the 'H-n.m.r. spectrum. The replacement of the anomeric acetoxy group in 1 with methylthio by heating for 6 h at 50" with (methylthio)trimethylsilane (see General methods) in dry 1,Zdichloroethane in the presence of trimethylsilyl trifluoromethane-* Synthetic Studies on Sialoglycoconjugates, Part 19. For Part 18, see ref. 1.