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Nicos A. Petasis

Harold E. and Lillian M. Moulton Chair and Professor of Chemistry

Office: LHI 219
Phone: (213) 740-6683
Fax: (213) 740-6684
Email: petasis@usc.edu
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Research Focus

 

Synthesis of Organic Molecules, New Synthetic Methods and Strategies

A central theme of our research is the study of new synthetic methods and strategies and their application to the synthesis of novel organic molecules that can lead to new pharmaceuticals or new materials.

A recent focus of our work has been the exploration of new chemistry of titanium and boron, elements with diverse reactivity that are also inexpensive and environmentally safe. The synthetic work is often aided by mechanistic and computational studies, which enhance our understanding of these processes and by a variety of synthetic applications that demonstrate their synthetic utility. We are also pursuing the synthesis of a variety of novel organic molecules. The physical and biological properties of these compounds are then studied in collaboration with other researchers. In this manner, the exploration of novel synthetic reactions provides the setting for discovering new chemistry, while it produces new substances for technology, biology and medicine.

Since our research program combines organic synthesis with organometallic, mechanistic, computational, combinatorial, biological, and medicinal chemistry, it offers a broad and multidisciplinary experience.

New chemistry of organotitanium compounds

In recent years our major effort in this area has focussed on a new and synthetically useful method for the olefination of various carbonyl compounds by using dialkyl titanocene derivatives. This mild process is suitable for the olefination of not only aldehydes and ketones, but also various hetereoatom-substituted carbonyls. In addition to dimethyl titanocene, which is useful for carbonyl methylenations, similar reactivity is possible with other derivatives, including dibenzyl, bistrimethylsilylmethyl and biscyclopropyl titanocenes. Moreover, the use of alkenyl titanocenes allows the conversion of carbonyls to allenes. This chemistry is also extended to a number of synthetic applications by us and others, including some large scale applications in the pharmaceutical industry.

New chemistry of organoboron compounds

We are pursuing the development of new reactions of organoboronic acids, which are readily available, experimentally convenient and environmentally friendly synthetic intermediates. Thus, we have recently invented a new one-step multicomponent process involving an organoboronic acid, an amine and a carbonyl derivative, which can produce a variety of novel multifunctional molecules, including amines, amino acids, amino alcohols, amino sugars, peptidomimetics, and various heterocyclic systems. A number of variations of this chemistry are under investigation, including highly stereocontrolled methods.

Petasis Research Pic
New methods for combinatorial chemistry and catalysis

We are exploring the utility of novel multicomponent reactions for the generation of a variety of potentially bioactive molecules. Our studies involve a number of strategies that would allow the facile production of combinatorial libraries that may be useful for pharmaceutical and agrochemical applications. Also, by relying on some unique features of this methodology, we are pursuing the design and synthesis of novel ligands for asymmetric synthesis and catalysis.

New chemistry of lipoxins and other lipids

The lipoxins (LXA4, LXB4) are bioactive eicosanoids, derived via the combined action of lipoxygenases on arachidonic acid and play a key role in cell-cell interactions and the regulation of inflammatory signals. In recent years we have been involved in a collaborative effort aimed at the design, synthesis and biological investigation of a series of biostable lipoxin analogues. A number of these molecules were synthesized and shown to exhibit potent bioactivities, particularly against inflammation. Some of our synthetic work has led to the identification and study of two new lipoxins, which are triggered by aspirin and may be associated with some of its beneficial effects. We have also contributed to the elucidation of the mode of action of these biomolecules which involves novel signaling pathways via polyisoprenyl phosphates.

References

 
1. Methylenations of heteroatom-substituted carbonyls with dimethyl titanocene" Petasis, N. A.; Lu, S. -P. Tetrahedron Lett., 1995, 36, 2393.
2. New stereocontrolled synthesis of substituted tetrahydrofurans from 1,3-dioxolan-4-ones" Petasis, N. A.; Lu, S. -P. J. Am. Chem. Soc., 1995, 117, 6394.
3. Organotitanium compounds in organic synthesis" Petasis, N. A.; Lu, S. -P.; Bzowej, E. I.; Fu, D. -K.,Staszewski, J. P.; Akritopoulou-Zanze, I.; Patane, M. A.; Hu, Y. -H. Pure & Appl. Chem., 1996, 68, 667.
4. Allenation of carbonyl compounds with alkenyl titanocene derivatives" Petasis, N. A.; Hu, Y. -H. J. Org. Chem., 1997, 62, 782.
5. A new and practical synthesis of a-amino acids from alkenyl boronic acids" Petasis, N. A.; Zavialov, I. A. J. Am. Chem. Soc., 1997, 119, 445.
6. A new synthesis of a -arylglycines from aryl boronic acids" Petasis, N. A.; Goodman, A.; Zavialov, I. A. Tetrahedron, 1997, 53, 16463.
7. LipoxinA4 stable analogs are potent mimetics that stimulate human monocytes and THP- I cells via a G-protein linked lipoxin A4 receptor" Maddox, J. F. ; Hachicha, M.; Takano, T.; Petasis, N. A.; Fokin, V. V.; Serhan, C. N. J. Biol. Chem., 1997, 272, 6972.
8. A role for polyisoprenyl phosphates in intracellular signaling" Levy, B. D.; Petasis, N. A.; Serhan, C. N., Nature, 1997, 389, 985.
9. Highly stereocontrolled one-step synthesis of anti- b-amino alcohols from organoboronic acids, amines and a-hydroxy aldehydes” Petasis, N. A.; Zavialov, I. A. J. Am. Chem. Soc. , 1998, 120, 11798.
10. Polyisoprenyl phosphate (PIPP) signaling regulates phospholipase D activity: a “stop” signaling switch for aspirin-triggered lipoxin A4” Levy, B. D.; Fokin, V. V.; Clark, J. M.; Wakelam, M. O.; Petasis, N. A.; Serhan, C. N. FASEB Journal, 1999, 13, 903.

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