title: 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.
abstract: 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.
authors.affiliation: Pharmazeutisch-Chemisches Institut, Universität Heidelberg, Germany.
authors.forename: H P
authors.initials: HP
authors.lastname: Deigner
authors.forename: B
authors.initials: B
authors.lastname: Fyrnys
mesh_terms: D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D015394:Molecular Structure; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010743:Phospholipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D010743:Phospholipids; D010740:Phospholipases