Synthesis of 1-O-alkyl-sn-glycerols and fluorescently labeled analogs from 2.5 O methylene D mannitol as precursor

Article abstract of DOI:10.1016/0009-3084(93)90036-3

A new approach employing 2.5 O methylene D mannitol as precursor for the synthesis of naturally occurring and fluorescently labeled alkyl glycerols is described. From 2.5 O methylene D mannitol, which was prepared according to the method of Ness et al. [1], 2,2-0-methylene-bis-(3-O-trityl)-sn-glycerol, the central product, was synthesized to an enantiomerically pure molecule in four steps. 1-O-hexadecyl-sn-glycerol was prepared by condensation of hexadecyl methanesulfonate with the central product and by subsequent detritylation and cleavage of the methylene bridge. From the alkyl glycerol the different lipid classes can be synthesized by well known strategies. To form fluorescently labeled analogs of alkyl glycerols the fluorescence marker 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) was linked with the ω-amino group of 1-O-(12-aminododecyl)-sn-grycerol. Therefore the central product was condensed with 12-N-t-BOC-aminododecyl methanesulfonate. The methylene bridge, the trityl groups and the BOC protection group were cleaved with boron trifluoride/methanol in one step. 1-O-(12-NBD-aminododecyl)-sn-grycerol is useful as a biochemical substrate to build up fluorescently labeled neutral lipids and phospholipids.