Synthesis of (R,S)-(5Z,8E,10E)-12-hydroxyheptadeca-5,8,10-trienoic acid and of (R,S), and (S)-(5Z,8Z,10E,14Z)-12-hydroxyeicosa-5,8,10,14-tetraenoic acid and their racemic 5,6,8,9-tetradeuterioisomers

Abstract

(5Z,8Z,10E,14E)-12-Hydroxyeicosa-5,8,10,14-tetraenoic acid [(S) and (R,S)-enantiomers], (R,S)-(5Z,8Z,10E,14Z)-12-hydroxy-5,6,8,9-tetradeuterio-5,8,10,14-tetraenoic acid, (R,S)-(5Z,8E,10E)-12-hydroxyheptadeca-5,8,10-trienoic acid, and (R,S)-(5Z,8E,10E)-12-hydroxy-5,6,8,9-tetradeuterioheptadeca-5,8,10-trienoic acid have been prepared by total synthesis. Deuterium was introduced at selected sites by partial reduction. All the acids were prepared from the common intermediate ethyl 10,10-diethoxydeca-5,8-dienoate. The c.d. spectrum of (S)-(7h) confirmed its identity with the natural product.

The mechanism of the reaction of heptynyl-lithium with (S)-1-chloro-2,3-epoxypropane has been shown to be by attack on the epoxide group, with subsequent recyclisation of the chloroalkoxide to give (S)-1,2-epoxydec-4-yne.