Divergent syntheses of all stereoisomers of phytosphingosine and their use in the construction of a ceramide library

Sphingolipids such as ceramide and sphingosine-1-phosphate have recently attracted intense research interests because of their functional roles as signaling molecules in many important physiological processes, such as growth arrest, apoptosis, and inflammatory responses, and cell proliferation, vascular maturation and trafficking of lymphocytes. The well-defined modular structures of ceramides and related glycosylceramides are ideally amenable to library formation for medicinal chemistry investigation. We have developed divergent synthetic routes to all eight phytosphingosine stereoisomers and then proceeded to prepare phytosphingosine-based ceramide library composed of more than 500 compounds.

Graphical abstractA ceramide library of 8 cores × 80 acyl tails.Figure optionsDownload full-size imageDownload as PowerPoint slide