1976 B.S. Vanderbilt University 1979 M.S. Tufts University 1982 Ph.D. Tufts University 1982-1985 Postdoctoral Fellow, Harvard University

Organic Chemistry

The long term goals of our research are focused at the interface of chemistry and biology. We are interested in solving problems in biomedicine using the techniques and application of synthetic organic, medicinal and natural products chemistry. Toward our goals in biomedicine we concentrate our efforts in the following three areas of organic chemistry: (1) the development of new methods and strategy which are applicable to the synthesis of biologically active compounds; (2) the total synthesis of a wide range of complex molecules including natural products, pharmaceutical leads and their analogues; and (3) the isolation and discovery of biologically active compounds from natural sources. Within our objectives in item 1 (above), we have had a long-term collaboration with the Clinical Pharmacology Section of the National Cancer Institute in which we have synthesized metabolites and analogues of thalidomide, a small-molecule immunomodulator and angiogenesis inhibitor. The derivatives and analogues of thalidomide were stereospecifically synthesized in order to ascertain the mode of action and the molecular target of this small molecule. Ultimately, the synthetic studies are leading to analogues of thalidomide which are more potent, but which have less undesirable side effects than the parent compound. In the neurosciences area we have completed an enantioselective synthesis of both optical isomers of a key intermediate in preparing the histrionicotoxins, a group of compounds which are isolated for the neurotoxic Amazon “poison dart” frogs. One of our present natural products projects (under item 3, above) entails the isolation, neurotoxicity assays and synthesis of a series of naturally-occurring compounds called acetogenins from the North American paw paw tree Asimina triloba. The isolation, purification and structural confirmation of the natural products has been conducted in collaboration with the Neurosciences Department within the University of Louisville School of Medicine. In the area of anti-infectives (under 1), we are designing and synthesizing an array of nitrogen and nitrogen/oxygen heterocyclic scaffolds bearing acetylenic and azido groups for use in the so-called "click reaction." The multiply-connected scaffolds have proven to be effective for inhibiting micro-organisms working in tandem to produce biofilms necessary for their establishment and survival.

Oxazoles for Click Chemistry II: Synthesis of Extended Heterocyclic Scaffolds P. C. Patil, F. A. Luzzio* and D. R. Demuth Tetrahedron Letters Symposia-in-Print (In Press).

Preparation of Azidoaryl- and Azidoalkyloxazoles for Click Chemistry C. M. Loner, F.A. Luzzio* and D. R. Demuth Tetrahedron Letters 2012, 53, 5641-5644.

1,3-Oxidative Transpositions of Allylic Alcohols in Organic Synthesis F.A. Luzzio Tetrahedron, 2012, 68, 5323- 5339.

Tandem Henry/oxa-Michael Route to the 1,3-Disubstituted-1,3-Dihydrobenzo[c]furan System F. A. Luzzio* and Otome E. Okoromoba Tetrahedron Lett. 2011, 52, 6530-6533.

Annonacin in Asimina triloba fruit: Implication for Neurotoxicity L. F. Potts, F. A. Luzzio, S. C. Smith, M. Hetman, P. Champy, I. Litvan* NeuroToxicology 2012, 33, 53-58 .

A Direct Arylation-Oxidation Route to 3-Arylisoindolinone Inhibitors of MDM2-p53 Interaction R. K. Dempster and F. A. Luzzio* Tetrahedron Lett. 2011, 52, 4992-4995.

Synthetically-Useful Bronsted Acid-Promoted Arylbenzyl Ether o-Benzylphenol Rearrangements F. A. Luzzio* and J. Chen J. Org. Chem. 2009, 74, 5629-5632

Preparation of Benzoheterocyclic Carbaldehydes F. A. Luzzio* and M. T. Wlodarczyk Tetrahedron Lett. 2009, 50, 580-583.

Efficient Preparation and Processing of the 4-Methoxybenzyl (PMB) Group for Phenolic Protection Using Ultrasound F. A. Luzzio* and J. Chen J. Org. Chem. 2008, 73, 5621-5624

Ethyl-(Z)-2,3-difluoro-3-(tributylstannyl)acrylate; Ethyl-(E)-2,3-difluoro-3-(tributylstannyl)acrylate F. A. Luzzio Encyclopedia of Reagents for Organic Synthesis; e-Eros; Paquette, L. A. Ed., John Wiley and Sons, Ltd.; Chichester, 2008

Preparation of b-Phenylnitroethanes having Electron-Donating Aryl Substitution F. A. Luzzio*, M. T. Wlodarczyk, D. Y. Duveau, J. Chen Tetrahedron Lett., 2007, 48, 6704-6708

Pyridinium Chlorochromate F. A. Luzzio Encyclopedia of Reagents for Organic Synthesis; e-EROS; Paquette, L. A. Ed., John Wiley and Sons, Ltd.: Chichester, 2007

A Chiral Pool Approach Toward the Synthesis of Thalidomide Metabolites F. A. Luzzio*, D. Y. Duveau and W. D. Figg Heterocycles, 2006, 70, 321-334

The Radical-Induced Cyclopentannulation of Henry (Nitroaldol)-Derived Intermediates F. A. Luzzio*, J. P. Ott and D. Y. Duveau J. Org. Chem. 2006 71, 5027-5030

Synthesis of Racemic 5-Hydroxy-3-Phthalimidoglutarimide. A Metabolite of Thalidomide Isolated from Human Plasma F. A. Luzzio*, D. Y. Duveau, E. R. Lepper and W. D. Figg J. Org. Chem. 2005, 70, 10117-10120

Triacylamines, Imides (Diacylamines), and Related Compounds F. A. Luzzio Science of Synthesis, Houben-Weyl Methods of Molecular Transformations, Weinreb, S., Ed.; Georg Thieme Verlag: Stuttgart, 2005, pp 259-324

Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) of Thalidomide Analogs as Angiogenesis Inhibitors E. R. Lepper*, S. S. W. Ng, M. Gutschow, M. Weiss, T. K. Hecker, F. A. Luzzio, K. Eger and W. D. Figg J. Med. Chem. 2004, 47, 2219-2227

Thalidomide Analogues: Derivatives of an Orphan Drug with Diverse Biological Activity F. A. Luzzio* and W. D. Figg Expert Opin. Ther. Patents 2004, 14(2) 215-229

Thalidomide Metabolites and Analogs. Synthesis and Antiangiogenic Activity of the Teratogenic and TNF-Modulatory Thalidomide Analog 2-(2,6-Dioxopiperidine-3-yl) Phthalimidine F. A. Luzzio*; A. V. Mayorov; S. S. W. Ng; E. A. Kruger and W. D. Figg J. Med. Chem. 2003, 46, 3793-3799

Antiangiogenic Activity of N-Substituted and Tetrafluorinated Thalidomide Analogues S. S. W. Ng*, M. Gutschow, M. Weiss, S. Hauschildt, U. Teubert, T. K. Hecker, F. A. Luzzio, E. A. Kruger, K. Eger and W. D. Figg Cancer Research 2003, 63, 3189-3194