Synthetic studies towards the viridin family of steroidal antibiotics

Abstract

The viridin (2) family of fungal metabolites has been known for over 55 years, but it has been the subject of very few synthetic studies, mostly because of the difficulties associated with the synthesis of the ABE fragment 37. The intromolecular Diels-Alder (IMDA) methodology developed in our laboratory provides a fast route to napthofuranone 76, thus making the assembly of the ABE fragment a relatively simple matter. The Diels-Alder reactions of 76 and derived compounds have been examined as a possible route to 2, but very little success was obtained. Alternatively, the IMDA reactions of benzidanones have also been investigated, ultimately leading to the synthesis of the pentacyclic skeleton of viridin. Epoxidation and singlet oxygen and permanganate oxidations of model compounds were examined in attempts to install the carbonyl on ring A, but that could not be accomplished by any of these methods. Instead, use of diene 201b in the IMDA reaction followed by hydrolysis of the thioether moiety not only delivered the carbonyl in the desired position, but also led to the shortest synthesis of halenaquinone (38) reported to date.