Synthesis of Cyperolone and 3-epi-Cyperolone.

Abstract

[alpha]-Cyperone (II) was reduced to eudesma-4,ll-dien-3[beta]-ol(in), which was converted into 4[beta] 5[beta]-oxidoeudesm-ll-en-3[beta]-ol(V). Treatment of the epoxide (V) with boron trifluroide gave eudesm-ll-en-3-on-5[beta]-ol(DT) but no cyperolone (I). The epoxy-alcohol (V) was acetylated to afford the acetoxy-epoxide (XII) which on treatment with boron trifluroide yielded 5[alpha]-fluoro-3[beta]-acetox-yeudesm-ll-en-4[beta]-ol(XTV) and l(R)-isopropenyl-3-(l-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 trifluroide to yield cyper-ll-ene-3,4-dione (XVI). On reduction the dione (XVI) afforded mainly cyper-11-ene-3[beta],4[xi]-diol(XIX) and cyper-ll-ene-3[alpha],4[xi]-diol(XX). The diol (XLX) was transformed to the 3[beta]-acetoxycyper-ll-en-4-one (XXIV) via 3[beta]-acetoxycyper-ll-en-4[xi]-ol (XXII). Alkaline-catalyzed hydrolysis of the acetate (XXIV) furnished cyperolone (I). The diol (XX) was converted into 3[beta]-acetoxycyper-ll-en-4-one (XXVII) via 3[beta]-acetoxycyper-ll-en-4[xi]-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).