Tumor Inhibitors. XXXIX. Active Principles of Acnistus arborescens. Isolation and Structural and Spectral Studies of Withaferin A and Withacnistin

Evidence is presented for assignment of structure for two cytotoxic compounds from Acnistus arborescens (L.), withaferin A (4a), and withacnistin (14a). Withaferin A (4a) was converted to the diacetate 4b, the ene-dione 5, and the methanol adduct 9, and the functional groups of each were characterized. The complete structure and stereochemistry of 4a were established by X-ray crystallographic analysis of the monoacetate p-bromobenzoate 4c. A detailed discussion of the nmr and mass spectral data is presented for the cited compounds and their derivatives. The structure of withacnistin (14a) was deduced, largely on the basis of ORD, nmr, and mass spectral comparison with 4a and its derivatives, as well as by nmr solvent shift data. Conversion to the acetate 14b, the methanol adduct 15a, and the deacetyl methanol adduct 15c supported the structural assignment. A small quantity of loliolide (11) was also isolated.