From lactose towards a novel galactosylated cyclooctenone.

Lactose was converted into a disaccharide precursor incorporating an allyl vinyl ether substructure within the glucose residue by vinylation, regioselective silylation, tosylation and subsequent elimination. The thermal Claisen rearrangement led to a novel galactosylated cyclooctenone exhibiting a boat-chair conformation.

Novel synthesis of alpha-galactosyl-ceramides and confirmation of their powerful NKT cell agonist activity.

alpha-Galactosyl-ceramide (1) has been identified as a powerful modulator of immunological processes through its capacity to bind CD1d molecules and specifically activate invariant natural killer (NK)-like T cells (iNKT cells). This paper describes the synthesis of 1, the analogous alpha-galactosyl-ceramide 3, and its short chain analogue 'OCH' (2), by use of the 4,6-di-O-tert-butylsilylene (DTBS) protecting group to produce a powerful alpha-galactosylating agent. In vivo experiments confirmed these compounds to be potent and selective activators of iNKT cells in a CD1d-dependent manner, each inducing a unique profile of cytokine release. This synthesis strategy will permit the generation of novel derivatives for use in the study of the mechanism of iNKT cell activation.