2,6-Disubstituted benzoates as neighboring groups for enhanced diastereoselectivity in beta-galactosylation reactions: synthesis of beta-1,3-linked oligogalactosides related to arabinogalactan proteins.

Arabinogalactan proteins (AGPs) are plant glycoproteins which contain a beta-1,3-linked galactan core. The synthesis of the beta-galactopyranose-1,3-beta-galactopyranose linkage using various 2-O-acyl-protected glycosyl donors has been plagued with poor stereoselectivity and side reactions including orthoester formation and transesterification of the 2-O-acyl group from the donor to the acceptor. We have investigated the use of 2,6-disubstituted benzoyl groups as bulky neighboring groups on the glycosyl donor. A 2,4,6-trimethylbenzoyl group was found to be optimal and enabled the formation of the beta-galactopyranose-1,3-beta-galactopyranose linkage to disarmed ester-protected acceptors, suppressing transesterification and reducing orthoester formation while enhancing the beta-selectivity of galactosylation reactions. A series of beta-1,3-linked oligogalactosides were prepared and elaborated to neoglycoconjugates for the study of AGP biosynthesis and AGP binding proteins.