Total synthesis of (+)-tedanolide

Abstract

This dissertation describes the synthetic studies culminating in the Smith total synthesis of (+)-tedanolide, a potent cytotoxic marine macrolide. Chapter one provides an introduction to the tedanolide family of natural products. Specifically, the isolation, structure elucidation, and biological activity of the tedanolides are discussed. Furthermore, a review of relevant synthetic work by other groups towards the tedanolides is summarized.* Chapter two provides a critical analysis of our synthetic approach to the (+)-tedanolide (1) and describes the synthesis of two major subtargets: (1) the common advanced C(1)-C(11) dithiane (−)- 26 for both (+)-tedanolide (1) and (+)-13-deoxytedanolide (2), via the iterative Evans syn-aldol reaction and stereocontrolled union of fragment (+)-21 and bidirectional linchpin (−)-22; (2) the C(12)-C(23) epoxide (+)- 178 via the efficient and highly convergent union of fragment (+)- 220 and (+)-221.* Chapter three describes the construction of the carbon framework of tedanolide (1) via the union of the dithiane linchpin (−)-26 with the requisite epoxide (+)-178, and the completion of the total synthesis of (+)-tedanolide (1).* *Please refer to dissertation for diagrams