Glycosylation under thermodynamic control:: Synthesis of the di- and the hexasaccharide fragments of the O-SP of Vibrio cholerae O:1 serotype Ogawa from fully functionalized building blocks

The known 5-(methoxycarbonyl)pentyl alpha-glycoside of the hexasaccharide of the O-SP of Vibrio cholerae 0:1, serotype Ogawa 31 was newly prepared from side-chain-equipped disaccharide building blocks. The intermediate tetrasaccharide 25 was prepared from the disaccharide glycosyl acceptor 11 and the (1 -> 2)-linked disaccharide thioglycoside glycosyl donor 8, having a (non-participating) saccharide moiety at C-2 in the downstream end. When performed conventionally (at room or at sub 0 degrees C temperatures), glycosylations with 11, carried out without anchimeric assistance, showed poor stereoselectivity but the formation of the 1,2-trans-glycosidic linkage could be markedly improved through thermodynamic control. This synthetic strategy towards 31 was more efficient than the step-wise approach, which was based on iterative glycosylation of 11 with 5 followed by delevulinoylation. Thermodynamic control improved considerably the yields of glycosylation of tetrasaccharide glycosyl acceptor 26 with disaccharide donor 18, to give the fully protected hexasaccharide 28, and also a similar reaction of the thioglycoside 18 with methyl 5-hydroxyhexanoate, to afford the linker-equipped disaccharide 19. Sequential deacetylation and debenzylation of the hexasaccharide 28, and deprotection of one of its intermediates, 19, gave the target hexasaccharide 31, and the wanted disaccharide 22, respectively. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007).