A Diversity-Oriented Strategy for Chemical Synthesis of Glycosphingolipids: Synthesis of Glycosphingolipid LcGg4 and Its Analogues and Derivatives

A diversity-oriented strategy was developed for the synthesis of glycosphingolipids (GSLs). This strategy was highlighted by using a simple lactoside containing the core structures of GSL glycan and lipid as the universal starting material to obtain different synthetic targets upon stepwise elongation of the glycan via chemical glycosylations and on-site remodeling of the lipid via chemoselective cross-metathesis and N-acylation. The strategy was verified with the synthesis of a lacto-ganglio GSL, LcGg4, which is a biomarker of undifferentiated malignant myeloid cells, and a series of its analogues or derivatives carrying different sugar chains and unique functionalities or molecular labels. This synthetic strategy should be widely applicable and, therefore, be utilized to rapidly access various GSLs and related derivatives by using different donors for glycosylations and different substrates for lipid remodeling following each glycosylation.

Automated summary

The synthetic strategy utilizing a single starting material and stepwise elongation of the glycan, as well as on-site remodeling of the lipid, successfully synthesized GSL compounds with different functionalities and sugar chains.