Host: Division of Organic Chemistry, The Pharmaceutical Society of Japan
Wortmannin, furan-fused steroidal natural product, has been known to possess various bioactivities, and recently, has been reported to exhibit a specific PI3-kinase inhibitory activity. In this study, we undertook the development of a new short-step approach for the construction of the A, B, E ring-system, which is thought to be a pharmacophore structure of wortmannin. The benzocyclobutene derivative containing furanyl side chain was prepared from readily available 1-cyano-5-methoxybenzocyclobutene in 3 steps. This compound was subjected to thermal ring-opening to form o-quinodimethane, which successively underwent intramolecular cycloaddition to afford the furan-fused tetracyclic compound as a mixture of two diastereomers. After desilylation, these isomers could be separated and were oxidized in a three-step sequence to afford the E-aromatized compound. Subsequent chemical transformations are now in progress.
