Mixed-chain phosphatidylcholine analogues modified in the choline moiety: preparation of isomerically pure phospholipids with bulky head groups and one acyl chain twice as long as the other

Abstract

Diacylphosphatidylcholines were synthesized with widely different acyl chain lengths and bulky head groups. Lysophosphatidylcholine was acylated at room temperature within 6 h with a 10-fold molar excess of fatty acid anhydride in dry, alcohol-free chloroform in the presence of 1.2 equivalents of 4-pyrrolidinopyridine as a catalyst, affording the mixed-acid phosphatidylcholines with widely different chain lengths in more than 90% yield and with less than 1% acyl migration. The syntheses of isomerically pure 1-stearoyl-2-decanoyl- and 1-stearoyl-2-undecenoyl(Δ 10)-sn-glycero-3-phosphocholines C(18 : 0)/C(10 : 0)-PC and C(18 : 0)/C(11 : 1Δ 10)-PC, respectively), followed by conversion to various head-group analogues, are illustrated here. The transition peak widths at half-height of the endotherms obtained by differential scanning calorimetry are consistent with very high isomeric purity. Phospholipase D from Streptomyces chromofuscus was used as a catalyst in the hydrolysis of C(18 : 0)/C(10 : 0)-PC to give the corresponding phosphatidic acid in quantitative yield. The latter compound was condensed with 10 molar equivalents of various N, N, N-trialkylammonium alkanols (as their p-toluenesulfonate or tetraphenylborate salt) in the presence of trichloroacetonitrile in dry pyridine under nitrogen atmosphere to yield the C(18 : 0)/C(10 : 0) phospholipids bearing modified head groups, which were purified by flash chromatography.