Efficient intramolecular glycosylation supported by a rigid spacer

The m-xylylene moiety was employed as rigid spacer in intramolecular glycos ide bond formation. Fifteen-membered macrocycle formation starting from 6-O -linked donor and 6- and 4-O-linked acceptor (5a,b, 6b) led exclusively to beta(1-4)- and beta(1-6)-linked compounds 7 beta and 8 beta, respectively, which gave cellobioside and gentiobioside derivatives. The glycosylation yi elds could be improved by 14-membered macrocycle formation. In the four cas es studied, the donor was 6-O-linked to the spacer. For the acceptor linkag e to the spacer and the accepting hydroxy group, relative D-/L-threo- and D -/L-erythro-arrangements were chosen. Standard glycosylation conditions led in three cases (13, 14, 23) only to beta-linkage in high yield (16 beta, 1 7 beta, 25 beta). For the transformation of 24, having a D-erythro-arrangem ent in the acceptor moiety, the alpha-anomer 26 alpha was preferentially ob tained. Limitation of the conformational space of the donor and the accepto r as in 31, which is stereochemically identical with 24, led to the corresp onding alpha-glycoside 32 alpha in 87% yield. Synthesis of a pseudo mirror image of 23 [having 6-(D)/3-(D-threo)-arrangement], namely 35, having 3(L)/ 6-(L-threo)-arrangement of the donor and acceptor moieties, expectedly gave only alpha-glycoside 36 alpha in very high yield. Thus, the efficiency and versatility of this conceptual approach to intramolecular glycoside bond f ormation is exhibited.