Efficient Intramolecular Glycosylation Supported by a Rigid Spacer

The m -xylylene moiety was employed as rigid spacer in intramolecular glycoside 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 β(1-4)- and β(1-6)-linked compounds 7 β and 8 β, respectively, which gave cellobioside and gentiobioside derivatives. The glycosylation yields could be improved by 14-membered macrocycle formation. In the four cases studied, the donor was 6- O -linked to the spacer. For the acceptor linkage 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 β-linkage in high yield ( 16 β, 17 β, 25 β). For the transformation of 24, having a d - erythro -arrangement in the acceptor moiety, the α-anomer 26 α was preferentially obtained. Limitation of the conformational space of the donor and the acceptor as in 31, which is stereochemically identical with 24, led to the corresponding α-glycoside 32 α 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 α-glycoside 36 α in very high yield. Thus, the efficiency and versatility of this conceptual approach to intramolecular glycoside bond formation is exhibited.