Synthesis of Cyperolone and 3-epi-Cyperolone.

Abstract

α-Cyperone (II) was reduced to eudesma-4, 11-dien-3β-ol (III), which was converted into 4β, 5β-oxidoeudesm-11-en-3β-ol (V). Treatment of the epoxide (V) with boron trifluoride gave eudesm-11-en-3-on-5β-ol (IX) but no cyperolone (I). The epoxy-alcohol (V) was acetylated to afford the acetoxy-epoxide (XII) which on treatment with boron trifluoride yielded 5α-fluoro-3β-acetoxyeudesm-11-en-4β-ol (XIV) and 1 (R)-isopropenyl-3-(1-methyl-4 (S)-acetoxy-5-oxohexylidene) cyclopentane (XV) but no cyperolone acetate (XXIV). Oxidation of the epoxy-alcohol (V) gave the keto-epoxide (VIII) which was treated with boron trifluoride to yield cyper-11-ene-3, 4-dione (XVI). On reduction the dione (XVI) afforded mainly cyper-11-ene-3β, 4ξ-diol (XIX) and cyper-11-ene-3α, 4ξ-diol (XX). The diol (XIX) was transformed to the 3β-acetoxycyper-11-en-4-one (XXIV) via 3β-acetoxycyper-11-en-4ξ-ol (XXII). Alkaline-catalyzed hydrolysis of the acetate (XXIV) furnished cyperolone (I). The diol (XX) was converted into 3β-acetoxycyper-11-en-4-one (XXVII) via 3β-acetoxycyper-11-en-4ξ-ol (XXV). When hydrolyzed with an excess of alkali the acetate (XXVII) gave cyperolone (I), while hydrolysis with an insufficient amount of alkali produced 3-epi-cyperolone (XXVIII). On alkaline treatment, 3-epi-cyperolone (XXVIII) was epimerized to give cyperolone (I).