Synthesis and some properties of constrained short-chain phosphatidylcholine analogues: (+)- and (−)-(1,3/2)-1- O-(phosphocholine)-2,3- O-dihexyanoylcyclopentane-1,2,3-triol

• Published in: Chemistry and physics of lipids Vol. 46; no. 3; pp. 157 - 164
• Main Authors: Barlow, P.N., Vidal, J.-C., Lister, M.D., Hancock, A.J., Sigler, P.B.
• Format: Journal Article
• Language: English
• Published: Elsevier Ireland Ltd 1988
• Subjects: constrained phosphatidylcholines; enantiomeric specificity; phosphatidylcholine synthesis; phospholipase A 2; phospholipid conformation; enantiomeric specificity; phosphatidylcholine synthesis; constrained phosphatidylcholines; phospholipase A 2; phospholipid conformation
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/0009-3084(88)90017-5

Reported herein is the synthesis of (+)- and (−)-(1,3/2)-1- O-(phosphocholine)-2,3- O-dihexanoylcyclopentane-1,2,3-triol. These are the enantiomers of a contrained analogue of dihexanoylphosphatidylcholine in which the glycerol backbone is replaced by all- trans cyclopentane-1,2,3-triol. Evidence is presented to demonstrate that the (−)-enantiomer is a substrate for phospholipase A 2 (PLA 2) ( Crotalus atrox) while the (+)-enantiomer is not. This strict enantiomeric (and positional) specificity was exploited in conjunction with a novel application of DEAE-cellulose column chromatography, to achieve racemic resolution with an excellent yield. The constrained backbone geometry, and the experimentally accessible critical micellar concentration (CMC) of these analogues should render them useful probes for assessing the contribution of substrate conformation and felxibility to the catalytic efficiency of PLA 2.