Synthesis of Stable Dolichylphosphomannose Analogues

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AbstractFour oleyl or dolichyl thiophosphate esters 16, 17, 21, and 22, analogues of Dol‐P‐Man possessing C(1)S and/or PS bonds, were synthesized as potential inhibitors of mannosyl transferases operating in the endoplasmic reticulum (ER). The β‐mannosyl derivatives were prepared by a Mitsunobu reaction of 2,3,4,6‐tetra‐O‐acetyl‐α‐D‐mannopyranose (1) with the thiophosphate 2 that provided O‐ and S‐glycosides with good‐to‐excellent diastereoselectivity. A second route to β‐mannosyl derivatives is based on the phosphitylation of the β‐D‐mannopyranosyl thiol 3 with the phosphoramidites 4a and 4b. Oxidation of the intermediate oleyl thiophosphite with t‐BuOOH led to mono‐ and dithiophosphates. The thiophospholipids 16, 21, and 22 were inactive as inhibitors of the Man6(GlcNAc)2‐PP‐Dol glycolipid elongation.