Total Synthesis of α-1C-Galactosylceramide an Immunostimulatory C-Glycosphingolipid and Confirmation of the Stereochemistry in the First-Generation Synthesis

摘要

A non-isosteric α-C-glycoside analogue of KRN7000 (α-1C-GalCer, >1) was reported to induce a selective type of cytokine release in human invariant natural killer cells in vitro. We report here a very concise synthetic route to >1 and its analogue >1′. The key steps include olefin cross-metathesis, Sharpless asymmetric epoxidation, and epoxide opening by NaN3/NH4Cl. Inversion of configuration at the amide-bearing carbon in the phytosphingosine backbone constructed by epoxide opening in our previous synthesis of >1 was verified, indicating that remote group participation is not involved during the epoxide-opening reaction.