A general and stereoselective route to alpha- or beta-galactosphingolipids via a common four-carbon building block

A general synthetic strategy toward alpha- or beta-galactosylceramides and their analogues from 3-azido-2-O-benzyl-1-O-(4-methoxybenzyl)butane-1,2,4-triol is described. The key steps for the installation of the main lipid chain are either a diasteroselective alkynylation reaction yielding the 4R stereocenter of phytosphingosine or a Wittig olefination generating the trans double bond of sphingosine. The methodology allows the preparation of different glycolipids with variations in the structure of the sphingoid base. In particular, three alpha-GalCer-related compounds have been synthesized and evaluated for their ability to activate CD1d-restricted T-cells.