Synthesis and in vitro Evaluation of α‐GalCer Epimers

Abstract

alpha-GalCer (also known as KRN7000) is an immunomodulatory glycolipid that is known to potently activate invariant natural killer T (NKT) cells upon CD1d-mediated stimulation. Because Th1 and Th2 cytokines, which are released after alpha-GalCer presentation, antagonize each other's effects, alpha-GalCer analogues that induce a biased Th1/Th2 response are highly awaited. In this context, we report the synthesis and in vitro evaluation of alpha-Gal-D-xylo-Cer and two alpha-Gal-L-lyxo-Cer analogues, one with the natural acyl chain, the other with a truncated chain.

Catalytic Z-selective olefin cross-metathesis for natural product synthesis

“…Stereoselective synthesis of anti-tumor agent KRN7000xx,xxi underlines the utility of the method (Fig. 3).…”

Aminocyclitol‐Substituted Phytoceramides and their Effects on iNKT Cell Stimulation

“…a-GalCer simultaneously induces the expression of types Th1 and Th2 cytokines, which have opposite cell polarizing functions, and leads to the down regulation of TCR that determines an unresponsive phase before recovering homeostatic equilibrium. [7] To improve the biological properties of a-GalCer, different analogues have been synthesized, [8,9] with variations in the lipid chain, [10][11][12][13][14][15] or substitution of the galactose by other monosaccharides [6,16] or polysaccharides. [17,18] However, glycoside-modified a-GalCer analogues are scarce, consistent with the crucial interactions of galactose with CD1d and TCR proteins.…”

Structure-Activity Relationship Studies of Novel Glycosphingolipids That Stimulate Natural Killer T-Cells

“…5) also activated NKT cells, inducing similar levels of cytokines to 1. 39,84) In addition, both of the diastereomers of the 4-deoxy-4-amino analogs (19 and 20) showed moderate bioactivity. 85) These results indicate that the configuration at 4-position has no influence on showing potent bioactivity.…”