18. GOALS FOR FELLOWSHIP TRAINING AND CAREER After completion of my post-doctoral studies with Prof. Breslow, I plan to seek a professorship in the chemistry department of a research university. Not only will my time in the Breslow group expand my experience in conducting cuttingedge scientific research, it will also provide a unique opportunity to learn from one of the premier leaders in chemistry academia. Like the many other alumni from the Breslow group, my research cxperience under the mentoring of Dr. Breslow will be key in solidifying my understanding on how to lead a program exploring the frontiers of scientific research in anacademicenvironment. Bioorganic chemistry, biomirnetie chemistry,medicinalchemistry,physical organicchemistry 22. DESCRtPTION(Do not exceed space provkled) The goal of this proposal is the development of artificial P-450enzymes as a practical alternative to microbiological methods in the selective functionalization of steroids. Steroid pharmaceuticafs play 3 prominent rote in the treatment of diseases ranging from arthritis to neuronal disorders. The continued identification of exciting biological activities from novel steroid natural products suggests that the potential for steroid scaffold-based drugs is far from being exhausted. The current manufactureof steroid medicinals relies heavity upon the ability of microorganisms to selectively oxidize steroid scaffolds. This proposal outlines strategies to efficiently synthesize novel sets of geometrically diverse hetero- and homogeneous catalysts that will mimic, and potentially surpass. the site-selective microbiological functionalizition of steroids. In specific, groups of unique cyclophane thiols will be constructed in a modular fashion on polymer-support and then condensed with tetra(pentafluoropheny1)porphyrin (TFPP). These proposed cyclophanc- fluoroporphyrin conjugates were designed to address the limitations of current P-450mimics. namely (rl the proclivity toward oxidativedegradationand (2) the limited nngeof positions on the steroidscaffoldthat can be functionalized. PHS416-1 (Rev. 12198) Form Page 2 BB cc lndividual NRSAApplication Table of Contents ========================================Section End===========================================
