Synthesis and Enzymatic Phosphorylation of a Photoactivatable Dolichol Analogue

• Published in: Journal of the American Chemical Society Vol. 119; no. 45; pp. 10992 - 10999
• Main Authors: Grassi, D, Lippuner, V, Aebi, M, Brunner, J, Vasella, A
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.11.1997; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; YEAST; PHOSPHATE; KINASE-ACTIVITY; POLYPRENOLS; STEREOSPECIFIC SYNTHESIS; GLYCOPROTEIN-BIOSYNTHESIS; GLYCOSYLATION; BUILDING-BLOCK; SACCHAROMYCES-CEREVISIAE; CHAIN-LENGTH
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja9721677

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 β-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.