Rapid synthesis of 2-desoxy-2-amino-3-phosphocholine-glycerinic-acid-alkylester, 1-alkyl-1-desoxy- and 1- O-alkyl-2-desoxy-2-amino- sn-glycero-3-phosphocholines, -3-phospho- N, N′-dimethylethanolamine and -3-phospho-Fmoc-serine-methylester

• Published in: Chemistry and physics of lipids Vol. 61; no. 2; pp. 199 - 208
• Main Authors: Deigner, Hans-Peter, Fyrnys, Beatrix
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.04.1992; Elsevier Science
• Subjects: 2-amino-lysophospholipid analogs; 2-desoxy-2-amino- sn-glycerophospholipids; Chemistry; ether lipid; Exact sciences and technology; Lipids; Magnetic Resonance Spectroscopy; Methods; Molecular Structure; Organic chemistry; Phospholipases - antagonists & inhibitors; phospholipid; Phospholipids - chemical synthesis; Phospholipids - chemistry; Phospholipids - pharmacology; Preparations and properties; Spectrometry, Mass, Fast Atom Bombardment; 2-amino-lysophospholipid analogs; phospholipid; 2-desoxy-2-amino- sn-glycerophospholipids; ether lipid; Phosphatidylcholine; Phospholipid; Aminoether; Complex lipid; Analog
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/0009-3084(92)90013-F

A convenient sequence for the rapid synthesis of 2-desoxy-2-amino-3-phosphocholine-glycerinic-acid-alkylester, 1-alkyl-1-desoxy- and 1- O-alkyl-2-amino-2-desoxy-3-phospho- derivatives is described. Key steps are the reaction of 1-carbonyloxyalkyl-, 1-alkyl- or 1- O-alkyl-amino-alcohols with phosphorus oxychloride to 1-carbonyloxyalkyl-, 1-alkyl- or 4-substituted 2-chloro-2-oxo-1,3,2-oxazaphospholane followed by nucleophilic displacement with choline tosylate, 1-bromoethane-2-ol or Fmoc- l-serine-methylester and subsequent hydrolysis to 2-amino-lysophospholipids giving the desired compounds in yields ranging between 68% and 81%. Several 2-amino-lysophospholipid analogs can then be prepared by this synthetic scheme utilizing the same oxazaphospholane intermediate. A brief method for the preparation of 2-amino-3-hydroxy-propionic-acid-pentyl- and -octylester from l-serine is described, opening a facile access to chiral precursors of phospholipid analogs.