Synthesis and enzymatic phosphorylation of a photoactivatable dolichol analogue

The synthesis of the photochemical probes 6 and 7 is described. These photoprobes are analogues of dolichol and dolichol phosphate, obligatory intermediates in the N-linked glycosylation pathway in the endoplasmic reticulum. The synthesis of 6 and 7 follows a new strategy. It involves the sequential alkylation of a monoterpenoid hydroxysulfonyl dianion with allyl chlorides. The photoreactive group, a 3-(trifluoromethyl)-3-aryldiazirine, was connected to the hydroxylated methyl group of the beta-prenyl unit of the fully assembled polyprenyl chain. The photoactivatable dolichol analogue 6 is a substrate for dolichol kinase from yeast membranes, an essential enzyme involved in the N-linked glycosylation pathway.