RAPID SYNTHESIS OF 2-DEOXY-2-AMINO-3-PHOSPHOCHOLINE-GLYCERINIC-ACID-ALKYLESTER, 1-ALKYL-1-DEOXY-2-AMINO-SN-GLYCERO-3-PHOSPHOCHOLINES AND 1-O-ALKYL-2-DEOXY-2-AMINO-SN-GLYCERO-3-PHOSPHOCHOLINES, 3-PHOSPHO-N,N'-DIMETHYLETHANOLAMINE AND 3-PHOSPHO-FMOC-SERINE-METHYLESTER

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.