A divergent synthesis of lipid A and its chemically stable unnatural analogues

Article abstract of DOI:10.1246/bcsj.72.1377

Lipid A and its two chemically stable analogues, wherein the glycosidic phosphoryl groups in lipid A is replaced with 2-(phosphonooxy)ethyl or carboxymethyl groups, have been synthesized by an improved and divergent route via a common allyl glycoside intermediate in which the 4-hydroxy group was protected as a benzyl ether. The total yields were more than 20% for 11 or 12 steps starting from allyl 4,6-O-benzylidene-2-deoxy-2- (trichloroethoxycarbonylamino)-D-glucopyranoside. These synthetic chemically stable analogues induce interleukin-6 and tumor necrosis factor a in human peripheral whole blood cells with potencies comparable to those by natural- type synthetic lipid A. The Limulus activities of both analogues were found to be even stronger than the activity of the natural-type one.