Design and synthesis of a novel glycosphingolipid derived from polyhydroxy 2-pyrrolidinone and phytoceramide appended by a 1,​2,​3-​triazole linker

Abstract

Synthetic analogs of glycosphingolipids (GSLs) have been demonstrated as potential therapeutic interventions in certain patho-physiological conditions. This article reviews reports of various bioactive synthetic GSLs, emanated from the Bittman laboratory. KRN7000, a synthetic GSL which is a α-galactosylceramide (α-GalCer) is a potent immunomodulatory agent. Bittman et al. reported several modifications of C-glycosides of KRN7000 with an eye towards achieving selective cytokine response during iNKT cell activation. However, GSLs with azasugar variants were not explored which inspired us to derive a polyhydroxy 2-pyrrolidinone azasugar from d-galactose and append to the phytoceramide via a 1,2,3-triazole linker to afford GSL analog 12. This novel GSL analog 12 may be used to explore the immunomodulatory activity, and other biological activities against targets involving iminosugar or azasugar based therapeutics.

Keywords: 1,2,3-Triazole; 2-Pyrrolidinone; Azasugar; Click chemistry; Glycosphingolipid; KRN7000; Phytoceramide; α-Galactosylceramide.