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Frederick A.Luzzio


Frederick A.Luzzio
Division: Organic Chemistry
Specialty: Organic and Medicinal Chemistry
Phone: 502-852-7323
Laboratory: 502-852-6066

Education and Research Experience

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

Current Service

Executive Committee/Treasurer, International Society of Heterocyclic Chemistry


Research Interests

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. 

Publications (recent or significant):     

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-
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

Palladium (0)-Mediated Preparation of trans-4-Substituted-1-(Phthalimido)-2-Cyclopentenes
F. A. Luzzio* and A. V. Mayorov
Synlett, 2003, 4, 532-536.

Enzymatic Resolution of the 1,3,3-Trimethyl-2-Oxabicyclo[2.2.2] Octane (1,8-Cineole) System
F. A. Luzzio* and D. Y. Duveau
Tetrahedron: Asymmetry, 2002, 13, 1173-1180

The Henry Reaction: Recent Examples
F. A. Luzzio
Tetrahedron, 2001, 57, 915-945

A Rearrangement Route to Fenvaleric Acid
F. A. Luzzio* and R. W. Fitch
J. Prakt. Chem., 2000, 342 (5), 498-501

Thalidomide metabolites and analogs. Part II. Cyclic derivatives of 2-N-phthalimido-2S,3S (3-hydroxy) ornithine
F. A. Luzzio*, E. M. Thomas and W. D. Figg
Tetrahedron Lett. 2000, 41, 7151-7155

Thalidomide metabolites. Part 1: Derivatives of (+)-2-(N-phthalimido)-γ-hydroxyglutamic acid
F. A. Luzzio*, A. V. Mayorov and W. D. Figg
Tetrahedron Lett., 2000, 41, 2275-2278
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