Synthesis of glycerophosphonolipids containing aminoalkylphosphonic acids

Abstract

1,2-Di-O-octadecyl- and 1,2-di-O-hexadecanoyl-sn-glycerol 3-(2-aminoethyl)phosphonate (21) and (22) and the (3-aminopropyl)phosphonate analogues (23) and (24) were prepared with the aim of obtaining enzyme (lipase)-stable liposomes. New reactions were devised and classic methodologies were modified in order to transform D-mannitol (6) into optically pure 1,2-di-O-substituted sn-glycerols (12) and (13)(R = C₁₈H₃₇ and C₁₅H₃₁CO). Benzyloxycarbonylaminoalkylphosphonic acids (5a) and (5b) were then coupled with the glycerols by means of condensing reagents such as 2,4,6-tri-isopropylbenzenesulphonyl chloride. The resulting N-protected lipids were catalytically hydrogenated to furnish compounds (21)–(24) in overall yields of 10–20% from compound (6).