Synthetic approaches towards chiral leukotriene analogues

• Main Author: Rogers-Evans, Mark C.
• Published: Loughborough University 1989
• Subjects: 572; Leukotriene synthesis
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.329386

A review of the discovery, biological activity and chemical synthesis of the leukotrienes is presented, together with the latest developments in their structural modification to produce useful antagonists. Strategies are presented for the preparation of chiral leukotriene derivatives in which the characteristic triene unit is replaced by various aromatic groups and include: (i) The preparation and attempted separation of the racemic diastereomers of methyl S-hydroxy-6-(2-methoxycarbonyl- 2-amino-ethylthio > -6-phenylhexanoate; (ii) A chemical synthesis involving the Sharpless asymmetricepoxidation of (El-ethyl 4-hydroxy-6-phenylhex-S-enoate to (El-ethyl S( R).6(S)-epoxy-6-phenyl-4(S)-hydroxyhexanoate followed by selective de-oxygenation studies on the corresponding racemic epoxy alcohol to give (E}-ethyIS.6-epoxy-6-phenyl-hexanoate; iii An enzymic route utilizing the porcine pancreatic lipase catalysed hydrolysis of a number of racemic 3-alkyl-3-butanoyloxy- 1.2-epoxides to the corresponding chiral epoxy alcohols with various degrees of selectivity. one of the most useful being the completely enantioselective hydrolysis of the less polar diastereomer of· (E)-3-butanoyloxy-I.2-epoxy-I-phenylhexane. The more polar diastereomer was preferentially hydrolysed to l( R),2(S)-epoxy-I-phenylhexan-3-( R)-ol, as verified by Sharpless epoxidation of (E)-I-phenylhex-I-en-3-01.