people
|Faculty
|Paul Floreancig
 |
Paul Floreancig Department of Chemistry |
Projects in my research group focus primarily on two aspects of organic synthesis - the development of new chemical reactions and the total synthesis of complex molecules. Synthetic methods are designed to provide new strategic options for simplifying synthetic sequences, to display unique chemoselectivity, and to utilize readily renewable reagents that minimize the formation of toxic waste products. Total synthesis projects are selected with the objective of developing routes to structures that can be used to study processes of medicinal significance.
Activating otherwise inert chemical bonds in a transient and selective manner creates opportunities for designing powerful new chemical reactions. Noting the general stability of carbon-carbon s-bonds and the wealth of methods for their construction, my research group has begun a program in which electron transfer initiated carbon-carbon ?-bond activation serves to trigger new synthetic transformations. In particular, homobenzylic ethers and amides serve as the starting materials for electron transfer initiated cyclization (ETIC) reactions. In this approach, photoinitiated single electron oxidation of the substrates by the catalytic oxidant N-methylquinolinium hexafluorophosphate forms radical cation intermediates which undergo a facile displacement of a benzyl radical by pendent nucleophiles. In these reactions, potent electrophiles are formed from very stable functional groups in a chemoselective manner under non-acidic conditions, and dioxygen is used as the terminal oxidant. A range of oxygen- and nitrogen-containing heterocycles have been prepared with this method and recent advances have resulted in the formation of carbocyclic compounds. The neutral conditions employed in these reactions allow for the design of heterogenerative cascade processes in which displacement of the benzyl radical by an epoxide serves to create a new electrophile for the initiation of another cyclization. Future efforts in this area will focus on devising methods to enhance the stereoselectivity of these reactions toward the goal of using the method in natural product synthesis, and designing new substrate types in order to develop greater insights into the reactivity of radical cations and to further expand the range of structural types accessible through this method. A representative cascade cyclization and some of the synthetic targets that serve as our inspiration in designing applications of this method are shown below.
In this project the total syntheses of the orbiculin A and related natural products will be undertaken to provide access to scaffolds that precisely orient various functional groups around the molecule. These groups will be selected to alter specific physical and chemical properties that have been proposed to be important in P-gp inhibition. The information gained from this work will be used in the design and synthesis of structurally simplified P-gp inhibitors and in the synthesis of agents used to study the mechanism of inhibition exhibited by other classes of P-gp modulators. Orbiculin A and the related MDR-reversing agent Ejap-1 are shown below.
Awards
Research Innovation Award, Research Corporation, 2001; NIH Postdoctoral Fellowship, 1997-1999; Roche Award for Excellence in Organic Chemistry, 1995; Eli Lilly Fellowship, 1994-1995.
Selected Publications
"Gold-catalyzed heterocycle synthesis using homopropargylic ethers as latent electrophiles," Jung, H. H.; Floreancig, P. E., Organic Letters, 2006, 8, 1949-1951
"Oxidatively generated electrophiles as initiators of epoxide cascade cyclization processes," Kumar, V. S.; Wan, S. Y.; Aubele, D. L., Tetrahedron-Asymmetry, 2005, 16, 3570-3578
"Concise and stereoselective synthesis of the N-7-C-25 fragment of psymberin," Rech, J. C.; Floreancig, P. E., Organic Letters, 2005, 7, 5175-5178
"Stereochemical assignment of the C-1-C-6 fragment of psymberin by synthesis and natural product degradation," Green, M. E.; Rech, J. C.; Floreancig, P. E., Organic Letters, 2005, 7, 4117-4120
"Total synthesis of (+)-dactylolide through an efficient sequential peterson olefination and prins cyclization reaction," Aubele, D. L.; Wan, S. Y.; Floreancig, P. E., Angewandte Chemie-International Edition, 2005, 44, 3485-3488
"Oxidative cyclorelease from soluble polymeric supports," Liu, H.; Wan, S. Y.; Floreancig, P. E., Journal of Organic Chemistry, 2005, 70, 3814-3818
"Investigations of the Scope and Mechanism of the Tandem Hydroesterification/Lactonization Reaction," Wang, L.; Floreancig, P. E., Org. Lett., 2004, 6, 4207
"Structure-Reactivity Relationships in Oxidative Carbon-Carbon Bond Forming Reactions: A Mild and Efficient Approach to Stereoselective Syntheses of 2,6-Disubstituted Tetrahydropyrones," Wang, L.; Seiders, J. R.; Floreancig, P. E, J. Am. Chem. Soc., 2004, 126, 12596
"Catalytic Aerobic Generation of Acyliminium Ions through Electron-Transfer-Mediated Carbon-Carbon Bond Activation," Aubele, D. L.; Rech, J. C.; Floreancig, P. E., Adv. Synth. Catal., 2004, 346, 359
"Synthesis of the C16-C35 Fragment of Integramycin Using Olefin Hydroesterification as a Linchpin Reaction," Wang, L.; Floreancig, P. E., Org. Lett., 2004, 6, 569