The principal goals of this research program entail the discovery of new catalytic asymmetric transformations for organic synthesis. Synthetic reactions under investigation include Claisen rearrangements, Diels-Alder reactions, Friedel-Crafts reactions, and nitro-Mannich reactions. To achieve these goals, rational design and combinatorial approaches will be implemented. Design tools include QSSR modeling to accelerate chiral ligand screening and identify important ligand features. Transition structure calculations will be combined with functionality mapping and database searching to develop new hydrogen bonding catalysts.

Public Health Relevance

New reaction methods and new asymmetric methods will be developed. The resultant technologies will be broadly useful in other contexts thereby facilitating the discovery and generation of new pharmaceutical agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM087605-02
Application #
8152226
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2010-09-30
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
2
Fiscal Year
2011
Total Cost
$299,127
Indirect Cost
Name
University of Pennsylvania
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Lassalas, Pierrik; Gay, Bryant; Lasfargeas, Caroline et al. (2016) Structure Property Relationships of Carboxylic Acid Isosteres. J Med Chem 59:3183-203
VanGelder, Kelsey F; Wang, Melinda; Kozlowski, Marisa C (2015) Route to α-Aryl Phosphonoacetates: Useful Synthetic Precursors in the Horner-Wadsworth-Emmons Olefination. J Org Chem 80:10288-93
Curto, John M; Kozlowski, Marisa C (2015) Chemoselective activation of sp(3) vs sp(2) C-H bonds with Pd(II). J Am Chem Soc 137:18-21
Gutierrez, Osvaldo; Metil, Dattatray; Dwivedi, Namrata et al. (2015) Practical, asymmetric route to sitagliptin and derivatives: development and origin of diastereoselectivity. Org Lett 17:1742-5
Liu, Lei; Carroll, Patrick J; Kozlowski, Marisa C (2015) Vanadium-catalyzed regioselective oxidative coupling of 2-hydroxycarbazoles. Org Lett 17:508-11
VanGelder, Kelsey F; Kozlowski, Marisa C (2015) Palladium-Catalyzed α-Arylation of Aryl Nitromethanes. Org Lett 17:5748-51
Gutierrez, Osvaldo; Tellis, John C; Primer, David N et al. (2015) Nickel-catalyzed cross-coupling of photoredox-generated radicals: uncovering a general manifold for stereoconvergence in nickel-catalyzed cross-couplings. J Am Chem Soc 137:4896-9
Walvoord, Ryan R; Kozlowski, Marisa C (2015) Cinchonidinium acetate as a convenient catalyst for the asymmetric synthesis of cis-stilbenediamines. Tetrahedron Lett 56:3070-3074
Metz, Alison E; Ramalingam, Kailasham; Kozlowski, Marisa C (2015) Xanthene-4,5-diamine derivatives: a study of anion-binding catalysis. Tetrahedron Lett 56:5180-5184
Curto, John M; Dickstein, Joshua S; Berritt, Simon et al. (2014) Asymmetric synthesis of α-allyl-α-aryl α-amino acids by tandem alkylation/π-allylation of α-iminoesters. Org Lett 16:1948-51

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