N-Diphenylmethylene-Protected Glycosyl Acceptors. Selective β-O-Glycosylation to Form Lactosyl-threo-Ceramides

Article abstract of DOI:10.1021/jo00068a028

A series of N-diphenylmethylene-protected sphingosine derivatives was synthesized (e.g. 3a,b and 9a,b).These compounds are efficient glycosyl acceptors and were shown to undergo highly β-selective glycosylation using a modification of the Koenigs-Knorr reaction previously used in this laboratory for the synthesis of O-linked glycopeptides (none of the α-anomers were detected by either 1H or 13C NMR).The N-diphenylmethylene (Schiff base) protection imparts a favorable intramolecular hydrogen-bonding pattern (Ph2C=N:->H-O:).This intramolecular hydrogen-bonding enhances the nucleophilicity of the glycosyl acceptor relative to glycosyl acceptors with more conventional N-protection (i.e.Cbz, Boc, acyl etc.) The enhanced nucleophilicity allowed the glycosylation to be carried out under mild conditions (AgOTfl, CH2Cl2, rt overnight), and provided the corresponding β-glycosphingolipids 4a-c and 11a-d in excellent chemical yield (approximately 70percent).After glycosylation, selective acid-catalyzed hydrolysis of the Schiff base protecting group was accomplished without cleavage of the glycosidic bond or the carbohydrate acetate protection.N-Acylation with palmitoyl chloride, followed by Zemplen deacetylation (cat.NaOMe in MeOH), provided the two threo-β-lactosylceramide analogues 7a and 7b.These analogues possess the unnatural threo-configuration in the ceramide moiety and may prove useful in studies of the biosynthesis and cell surface composition of more complex glycosphingolipids.