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Synthesis of Stable Dolichylphosphomannose Analogues
Author(s) -
Kulesza Anna,
Frank Christian G.,
Aebi Markus,
Vasella Andrea
Publication year - 2004
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200490278
Subject(s) - thiophosphate , chemistry , glycolipid , endoplasmic reticulum , stereochemistry , glycoside , thiol , mitsunobu reaction , organic chemistry , biochemistry
Four oleyl or dolichyl thiophosphate esters 16, 17, 21 , and 22 , analogues of Dol‐P‐Man possessing C(1)S and/or PS 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 Man 6 (GlcNAc) 2 ‐PP‐Dol glycolipid elongation.