Stereocontrolled Synthesis of Lyso-phosphatidyl beta-D-Glucoside

摘要

Lyso-phosphatidyl beta-D-glucoside (lysoPtdGlc) is during embryonic development a neurite growth cone guidance cue associated with G-protein coupled receptor 55, and has been found to be involved in a variety of physiological and pathological events, including inflammatory pain, and cancer. Hence, the ability to prepare large quantities of lysoPtdGlc is an important objective. Herein, we report the convergent chemical synthesis of lysoPtdGlc and its glyceryl epimer (S-lysoPtdGlc). High stereocontrol during beta-glycosyl H-phosphonate construction was achieved using a microfluidic approach, and common but undesirable regioisomerization due to acyl migration on the glyceryl subunit was successfully suppressed during deprotection. Purification of the final product was optimized to obtain sufficiently large amounts of lysoPtdGlc and S-lysoPtdGlc for biological assaying purposes.