Continued Progress Towards Efficient Syntheses Of Cephalostatin North 1 Analogs

Jamieson, Daniel P. Ph.D., Purdue University, December 2013. Continued Progress Towards Efficient Syntheses of Cephalostatin North 1 Analogs. Major Professor: Philip L. Fuchs. The cephalostatins and ritterazines represent an intriguing class of marine natural products in both structure and biological activity, and the progress towards the synthesis of high valued analogs with a focus on process orientated methodology is described herein. Included in the pages to follow, is the further advancement of the ‘Red-Ox’ strategy toward the highly efficient synthesis of 25-epi-14,15-dihydro-North 1, Chapter 2. A short review focusing on the earlier efforts toward the main synthetic challenges of North 1 analogs and the lessons learned to propel the efficient stereoselective synthesis of anti-cancer spiroketals is presented. The development of a new ‘Plug and Play’ titanium(II) alkylidenation approach for the synthesis of α-functionalized spiroketals is presented in Chapter 3. Highlighting the new strategy, is the process efficient synthesis of the a key enol ether intermediate as the gateway to the synthesis of 26,27-dihydroxy North 1 and other spiroketal analogs. The use of silyl triflates for tandem one pot kinetic resolution of diastereomers is also presented.