The chemoselective O-glycosylation of alcohols in the presence of a phosphate diester and its application to the synthesis of oligomannosylated phosphatidyl inositols

Abstract

The glycosylation of hydroxyl groups in the presence of a phosphate diester and its use in the synthesis of oligomannosylated phosphatidiyl inositols are reported. Using a catalytic amount of TMSOTf as an activator for the glycosidation of glycosyl imidates in the presence of a primary alcohol and a phosphate diester provided the desired glycoside along with a glycosyl phosphnate. Complete glycosylation of the primary alcohol required a stoichiometric amount of TMSOTf or TBSOTf. We next examined an application of the method to the synthesis of the phosphatidylinositol mannosides, which are components in the mycobacterial cell wall envelope. Glycosylation of the primary alcohol at the C6 position of a 2,6-dimannosyl myo-inositol core containing a diacylated phosphatidyl lipid with glycosyl imidiates proceeded smoothly to provide multimannosylated inositol derivatives in good yields. However, the 4,6 diol mannoside was a poor acceptor in this reaction.