Cyclic platelet-activating factor analogues derived from 2-deoxy-D-erythro-pentose.
A method for the synthesis of chiral cyclic analogues of platelet-activating factor (PAF) is reported. Treatment of suitably substituted derivatives of 2-deoxy-D-erythro-pentose with phosphorus oxychloride, followed by choline p-toluenesulfonate generates cyclic phospholipids in good yield. Further chemical modification produces other compounds including optically active gamma-butyrolactones such as 2-deoxy-5-O-hexadecyl-3-O-phosphocholyl-D-erythro-pentono-1, 4-lactone and 2-deoxy-3-O-hexadecyl-5-O-phosphocholyl-D-erythro-pentono-1, 4-lactone. All phospholipids were poor antagonists of PAF-induced aggregation of human platelets, and two analogs were poor agonists. The chemistry presented should be useful for the syntheses of other conformationally restricted analogues of PAF.
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis*; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009904:Optical Rotation; D010429:Pentoses; D010972:Platelet Activating Factor / Q000031:analogs & derivatives*; D010974:Platelet Aggregation / Q000187:drug effects; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D005663:Furans; D007202:Indicators and Reagents; D010429:Pentoses; D010972:Platelet Activating Factor; D015107:4-Butyrolactone