Unusual withanolides from Physalis hispida (Waterf.) Cronquist

Withanolides are a group of modified C₂₈ ergostane-type steroids with a C-22, C-26 δ-lactone side chain. As part of our continuing search for unusual withanolides for SAR studies, we isolated and characterized nine new withanolides (1 – 9), withahisolides A-I, as well as nine known compounds (10 – 18) from the aerial parts of Physalis hispida. The structures of 1 – 9 were elucidated through a variety of spectroscopic techniques, while those of 1 and 2 were further confirmed by X-ray crystallographic analysis. Among the eight new withanolides (1 – 7, 9) with an unusual six-membered ring D, 1 – 3 are the first withanolides possessing non-aromatic six-membered ring D moieties. In addition, withanolide 8 represents a novel withanolide skeleton due to the absence of a C-13-C-17 bond within its steroidal nucleus.