The development of novel expeditious and efficient methodologies toward the synthesis of biologically significant heterocyclic compounds is planned. The proposed project consists of four major sections. The first section is devoted to the investigation and development of novel cycloisomerization approaches toward monocyclic and fused furans, pyrroles, and thiophenes, and to the development of cascade migration/cyclization methodologies en route to highly substituted heterocycles. The second section is directed toward investigation of the scope of the recently discovered transannulation reaction as a highly attractive modular approach to a variety of diverse heteroaromatic scaffolds. The third section covers transition metal-catalyzed functionalization of amphiphilic heterocyclic building blocks through nucleophilic or electrophilic cross-coupling reactions. The fourth section is aimed at development of new synthetic approaches for the rapid construction of naturally occurring and unnatural heterocyclic molecules of biological importance using methodologies developed in our laboratories. Synthetic targets for the proposed research include various diversely substituted indolizines not easily available by existing techniques, potential selective group V sPLA2 inhibitors; lamellarin D and its analogs, and novel lamellarin-campthothecin hybrid pentacyclic scaffolds, potential topoisomerase I inhibitors. ? ? The synthetic part of the proposed work toward selected targets is essential as it may lead to discovery of potent anti-inflammatory and anticancer agents. The methodological part of this proposal toward general and efficient methods for construction and functionalization of diverse fused heterocycles has even broader impact, as upon development, it would dramatically broaden the arsenal of libraries of biologically important molecules available for medicinal chemists and biologists, and will most certainly impact drug discovery research and related health-oriented sciences. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM064444-04
Application #
7195085
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Schwab, John M
Project Start
2001-12-01
Project End
2010-02-28
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
4
Fiscal Year
2007
Total Cost
$254,172
Indirect Cost
Name
University of Illinois at Chicago
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Shiroodi, Roohollah Kazem; Vera, Claudia I Rivera; Dudnik, Alexander S et al. (2015) Synthesis of furans and pyrroles via migratory and double migratory cycloisomerization reactions of homopropargylic aldehydes and imines. Tetrahedron Lett 56:3251-3254
Wang, Yang; Gevorgyan, Vladimir (2015) General method for the synthesis of salicylic acids from phenols through palladium-catalyzed silanol-directed C-H carboxylation. Angew Chem Int Ed Engl 54:2255-9
Helan, V; Gulevich, A V; Gevorgyan, V (2015) Cu-Catalyzed Transannulation Reaction of Pyridotriazoles with Terminal Alkynes under Aerobic Conditions: Efficient Synthesis of Indolizines. Chem Sci 6:1928-1931
Kazem Shiroodi, Roohollah; Soltani, Mohammad; Gevorgyan, Vladimir (2014) Gold-catalyzed 1,3-transposition of ynones. J Am Chem Soc 136:9882-5
Shi, Yi; Gulevich, Anton V; Gevorgyan, Vladimir (2014) Rhodium-catalyzed NH insertion of pyridyl carbenes derived from pyridotriazoles: a general and efficient approach to 2-picolylamines and imidazo[1,5-a]pyridines. Angew Chem Int Ed Engl 53:14191-5
Kuznetsov, Alexey; Gulevich, Anton V; Wink, Donald J et al. (2014) A new reactivity mode for the diazo group: diastereoselective 1,3-aminoalkylation reaction of ?-amino-?-diazoesters to give triazolines. Angew Chem Int Ed Engl 53:9021-5
Ghavtadze, Nugzar; Melkonyan, Ferdinand S; Gulevich, Anton V et al. (2014) Conversion of 1-alkenes into 1,4-diols through an auxiliary-mediated formal homoallylic C-H oxidation. Nat Chem 6:122-5
Parasram, Marvin; Iaroshenko, Viktor O; Gevorgyan, Vladimir (2014) Endo-selective Pd-catalyzed silyl methyl Heck reaction. J Am Chem Soc 136:17926-9
Shiroodi, Roohollah Kazem; Koleda, Olesja; Gevorgyan, Vladimir (2014) 1,2-boryl migration empowers regiodivergent synthesis of borylated furans. J Am Chem Soc 136:13146-9
Gulevich, Anton V; Gevorgyan, Vladimir (2013) Versatile reactivity of rhodium-iminocarbenes derived from N-sulfonyl triazoles. Angew Chem Int Ed Engl 52:1371-3

Showing the most recent 10 out of 67 publications