Synthesis of 1-O-alkyl-2-O-methyl-glycerophospholipids with potential antitumor activity

Farmaco. 1990 May;45(5):499-509.

Abstract

Some synthetic alkyl-lysophospholipid analogs have been described as a new class of immunopotentiating and antitumor agents. Among them, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine has been reported to possess the highest antitumor activity. A new method for the synthesis of this compound and of the ethanolamine- and serine-containing analog is reported. 1-Alkyl-2-methyl-rac-glycerol, prepared from 1,2-isopropylidene-glycerol, is phosphorylated and the intermediate is condensed either with N-t-BOC-protected ethanolamine or with N-t-BOC-protected serine benzhydryl ester. The choline-derivative is obtained by methylation with CH3I of the ethanolamine derivative. The same synthetic sequence has been used also for synthesizing compounds unsaturated at the fatty alkyl chain in position 1 of the glycerol moiety. Preliminary observation are reported on the selective cytolytic action of the compounds on a tumor cell line.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Cell Survival / drug effects
  • Chemical Phenomena
  • Chemistry
  • Lymphoma / pathology
  • Mice
  • Phospholipid Ethers / chemical synthesis*
  • Phospholipid Ethers / pharmacology
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / pathology

Substances

  • Antineoplastic Agents
  • Phospholipid Ethers
  • edelfosine