Part I. Total synthesis of (−)-clavosolide A. Part II. Synthesis of the western hemisphere of (+)-nodulisporic acid A

Abstract

The first part of the dissertation describes the total synthesis of the polyketide marine natural product (–)-clavosolide A utilizing the Petasis-Ferrier union/rearrangement tactic for the synthesis of the two central cis-tetrahydropyrans. A one-pot esterification/macrocyclization employing the Yamaguchi protocol, followed by Schmidt bis-glycosidation completed the synthesis of (–)-clavosolide A in a longest linear sequence of 17 steps from commercially available crotonaldehyde.

The second part of the dissertation describes the efforts toward the synthesis of the alkaloid (+)-nodulisporic acid A, in particular the synthesis of the Western hemisphere. These studies culminated with the development of a new and scalable second-generation synthesis of the Western fragment, which entailed several key steps: a solvent-free and chemoselective Heck coupling, Selectfluor^®-mediated iodination, SAMP-hydrazone Enders aldol reaction, peroxyselenious acid removal of the chiral hydrazone, and Nozaki-Takai-Hiyama-Kishi cyclization. The last section of Part II details the Stille cross-coupling/Buchwald-Hartwig cyclization studies between the Western hemisphere and an estrone-derived Eastern hemisphere analogue.