Stereoselective Synthesis of Diglycosyl Diacylglycerols with Glycosyl Donors Bearing a ß-Stereodirecting 2,3-Naphthalenedimethyl Protecting Group.

ABSTRACT

Diglycosyl diacylglycerols (DGDGs) are major components of Gram-positive bacterial plasma membranes and are involved in the immune response systems. The chemical synthesis of DGDGs has been highly demanded, as it will allow the elucidation of their biological functions at the molecular level. In this study, we have developed a novel ß-stereodirecting 2,3-naphthalenedimethyl (NapDM) protecting group that is orthogonal to protecting groups commonly used in oligosaccharide synthesis. The NapDM group can be easily cleaved under TFA-mediated acidic conditions. Futhermore, we demonstrated the application of this protecting group to an acyl protecting-group-free strategy by utilizing the NapDM group for the synthesis of DGDGs. This strategy features the use of the ß-stereodirecting NapDM group as an acid-cleavable permanent protecting group and late-stage glycosylation of monoglycosyl diacylglycerol acceptors, enabling the stereoselective synthesis of three different bacterial DGDGs with unsaturated fatty acid chain(s).