Synthesis 1989; 1989(1): 16-20
DOI: 10.1055/s-1989-27132
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Stereospecific Synthesis of 2-Substituted Ether Phospholipids

Suresh K. Bhatia* , Joseph Hajdu
  • *Department of Chemistry, California State University, Northridge, CA 91330, USA
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Publikationsdatum:
27. September 2002 (online)

A new stereospecific synthesis of biologically active 2-substituted ether phospholipids is reported. The synthesis is based upon 1) using D-α,β-isopropylideneglycerol-γ-tosylate to provide the chiral center, 2) introducing the sn-2-thio function by nucleophilic sulfur displacement of the p-nitrobenzenesulfonyl-activated secondary glycerol function, and 3) elaborating the sn-3-phosphorylcholine moiety either by the β-bromoethyl phosphodichloridate-trimethylamine sequence, or via phosphorylation using 2-chloro -2-oxo-1,3,2-dioxaphospholane followed by nucleophilic ring opening of the phosphotriester with trimethylamine. Through the use of intermediates that became available from the sequence new sn-2-thioacyl and sn-2-thiomethyl ether phospholipids were prepared. The synthetic compounds include chromogenic substrates of phospholipase A2 enzymes, a highly potent antihypertensive ether phospholipid and a structural analogue of antitumor active alkylphosphoglycerides. The synthetic methods developed have a great deal of flexibility providing convenient routes to a wide range of structurally variable ether phospholipids for physicochemical and enzymological studies.