|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
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
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
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
Thomas S, Sharma N, Golden EB, Cho H, Agarwal P, Gaffney KJ, Petasis NA, Chen TC, Hofman FM, Louie SG, Schönthal AH.
Preferential killing of triple-negative breast cancer cells in vitro and in vivo when pharmacological aggravators of endoplasmic reticulum stress are
combined with autophagy inhibitors. Cancer Letters, 2012, 325(1), 63-71. PMID: 22664238
Dalli J, Winkler JW, Colas RA, Arnardottir H, Cheng CYC, Chiang N, Petasis NA, Serhan CN.
Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents. Chemistry & Biology (Cell). 2013, 20(2), 188-201. PMC3583372.
Dalli J, Zhu M, Vlasenko NA, Deng B, Haeggström JZ, Petasis NA, Serhan CN.
The novel 13S,14S-epoxy-maresin is converted by human macrophages to maresin 1 (MaR1), inhibits leukotriene A4 hydrolase (LTA4H) and shifts
macrophage phenotype. FASEB J. 2013, 27, 2573-2583. PMC3688739.
of heteroatom-substituted carbonyls with dimethyl titanocene"
Petasis, N. A.; Lu, S. -P. Tetrahedron Lett., 1995, 36,
stereocontrolled synthesis of substituted tetrahydrofurans from
1,3-dioxolan-4-ones" Petasis, N. A.; Lu, S. -P. J. Am. Chem.
Soc., 1995, 117, 6394.
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,
of carbonyl compounds with alkenyl titanocene derivatives"
Petasis, N. A.; Hu, Y. -H. J. Org. Chem., 1997, 62,
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.
A new synthesis of a
-arylglycines from aryl boronic acids" Petasis, N. A.; Goodman, A.; Zavialov,
I. A. Tetrahedron, 1997, 53, 16463.
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,
role for polyisoprenyl phosphates in intracellular signaling"
Levy, B. D.; Petasis, N. A.; Serhan, C. N., Nature, 1997,
Highly stereocontrolled one-step synthesis of anti-
from organoboronic acids, amines and
a-hydroxy aldehydes Petasis, N. A.; Zavialov, I. A. J. Am. Chem. Soc.
, 1998, 120, 11798.
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.