Synthesis of the DFGH ring system of Type B Physalins: Highly Oxygenated, Cage-Shaped Molecules

摘要

Physalins, which are steroidal constituents isolated from Physalis plants, contain a unique 13,14-seco-16,24-cycloergos-tane skeleton. The structures of physalins A (1) and B(2; Scheme 1) were first determined in 1969, and so far phys- alins A-Z, I, and II have been identified. Physalins are characterized by a highly oxygenated, complex, fused-ring system. Type B physalins, such as physalin B (2), are composed of eight rings including an internal acetal ring (H ring, C(14)-O-C(27)-C(25)). Physalins show antitumor activity in vitro and in vivo. Furthermore, other unique activity of 2 has recently been reported. These include inhibition of hedgehog/GLI-mediated transcription, inhibition of PMA-induced (PMA = phorbol 12-myristate 13-acetate) NF-kB activation, antiinflammatory and immunomodulatory activity, and inhibition of the ubiquitin-proteasome pathway.