Chemoenzymatic synthesis of a tachykinin NK-2 antagonist

A non-peptide tachykinin antagonist has been synthesized in a short and eff icient four step sequence starting from a chiral enol acetate, which was ob tained in enantiomerically pure form by resolution using a lipase catalysed transesterification reaction. The biotransformation was optimized in terms of solvent, temperature and immobilization method used. Oxidative cleavage of the (+)-enol acetate to give the key aldehyde ester intermediate could be achieved indirectly by oxidative rearrangement to an enone followed by B aeyer-Villiger oxidation and ring opening, or by epoxidation, rearrangement and oxidative cleavage or most directly by ozonolysis. X-Ray crystallograp hic analysis of a camphanic ester derivative of an ester alcohol confirmed that the absolute configuration of the enol acetate was (S). (C) 2001 Publi shed by Elsevier Science Ltd.