Synthesis of Clavulone Derivatives. : Selective Cleavage of Ester Bonds and Elongation of α-Side Chain in Clavulone

Abstract

Several clavulone derivatives were synthesized from clavulone I (1) and clavulone II (2). The carboxylic acid 3 and 4-O-deacetyl derivative 4 were synthesized by selective enzymatic hydrolysis of 2 using porcine liver esterase and orange peel acetylesterase, respectively. From the carboxylic acid 3, the benzyl ester 5, tert-butyl ester 6 and amide 7 were prepared. The 12-O-deacetyl derivative 9 was synthesized by organicuprate reduction of the epoxide 8 which was prepared from 2. The derivatives 13-15, which possess an elongated α-side chain, were synthesized from 1 via the hemiacetal 12.