Progress toward the total synthesis of tedanolide and 13-deoxytedanolide

This thesis describes the Smith group\u27s synthetic efforts toward the tedanolides, marine natural products possessing potent cytotoxic activities. We envisioned that the use of dithianes as acyl anion equivalents could be exploited in a unified approach to both congeners. To this end, the synthetic strategy relied on the successful implementation of dithiane couplings with either an epoxide (for tedanolide) or an iodide (for 13-deoxytedanolide) to assemble the C(1–23) carbon backbone. Retrosynthetic disconnection of tedanolide (1) and 13-deoxytedanolide (2) thus suggested two major subtargets, C(1–11) dithiane 5 and the C(12–23) epoxide/iodide (3/4).* Chapter two describes the synthesis of the C(1–11) dithiane subtarget. Noteworthy in the synthesis of this fragment is the exploitation of the Evans aldol methodology to expediently construct C(3–7). Also discussed is the development and application of a novel linchpin, vinyl iodide 7 .* In chapter three, the preparation of a common intermediate (i.e., 8) for the synthesis of both tedanolide and 13-deoxytedanolide is described. The choice of protecting groups for the C(15), C(17), and C(29) hydroxyls proved crucial to the success of the synthesis.* Also discussed in chapter three is the conversion of this intermediate (i.e., 8) to the iodide coupling partner (4) and successful union with dithiane subtarget 5. The strategy to convert the coupled product (i.e., 9) to 13-deoxytedanolide is also described.* *Please refer to dissertation for diagrams