Synthesis of a Fluorinated Analogue of Anticancer Active Ether Lipids

Abstract

The synthesis of racemic 2'-(trimethylammonium)ethyl-3-hexadecyloxy-2-fluoro-2-(methoxymethyl)prop-1-yl-phosphate (6), a fluorinated analogue of an anticancer active ether lipid 5 was realized with 3% overall yield in a nine-step synthesis starting from 2-methylene-1,3-propanediol (7) using a bromofluorination as the key step. Both enantiomers of the precursor 8 of the ether lipid 6 were synthesized by lipase-catalyzed desymmetrization of the diacetate 17, either by hydrolysis (83% ee) or by lipase-catalyzed acetylation of the diol 22 (82% ee). The antitumor activity of 6 has been found in an in vivo model of the methylcholanthrene-induced fibrosarcoma of mice.