Efficient Syntheses Of A Series Of Glycosphingolipids

Glycosphingolipids (GSLs) are ubiquitous components of the cellular membranes of all eukaryotic cells. The scientific interest in GSLs has increased on account of the role they participate in various cell-surface related processes, such as cell differentiation, transmembrane signaling, cell recognition, and toxin binding. Such cellar recognition events are common to cancer, allergy, viral infection, inflammation, and autoimmune disease. Each of these events is executed by a specific glycosphingolipid such as a ganglioside, tumor antigen, or viral receptor. This exquisite degree of specificity suggests that glycosphingolipid analogues could be suitable candidates for new drugs, thus necessitating efficient synthetic routes to pure glycosphingolipids and their derivatives. Here, the synthesis of a series of glycosphingolipids was reported.1. A flexible synthesis of sphingosine and ceramide was founded, starting from D-xylose and using CuCN catalyzed cross-coupling reaction of an allylic mesylate with a Grignard reagent to accomplish formation of the double bond with an exclusive E configuration and chain extension in one step. D-xylose was protected as 1,2-O-isopropylidene-D-xylose (40) and transformed via 41 into the known 3,5-dibenzyl-D-xylose (42). The Witting reaction of 42 with 2 equivalents of methylidenetriphenylphosphorane afforded the olefin 43 (69%), which was allowed to react with methanesulfonyl chloride to give the dimesylate 44 the precursor for the alkylation reaction. Reaction of the allylic mesylate 44 with the Grignard reagent prepared from bromododecane in the presence of 5 mol % CuCN smoothly afforded the desired compound 45. Then the mesylate 45 was converted into the natural product D-erythro-sphingosine (1) by a series of functional group transformation involving: SN2 replacement of the mesylate group in compound 10 by sodium azide, reduction of the resultant azide group of 10...