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 #
5R01GM087605-03
Application #
8307995
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2010-09-30
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2012
Total Cost
$301,114
Indirect Cost
$103,114
Name
University of Pennsylvania
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Curto, John M; Dickstein, Joshua S; Berritt, Simon et al. (2014) Asymmetric synthesis of ?-allyl-?-aryl ?-amino acids by tandem alkylation/?-allylation of ?-iminoesters. Org Lett 16:1948-51
Curto, John M; Kozlowski, Marisa C (2014) ?-Allyl-?-aryl ?-amino esters in the asymmetric synthesis of acyclic and cyclic amino acid derivatives by alkene metathesis. J Org Chem 79:5359-64
Walvoord, Ryan R; Huynh, Phuong N H; Kozlowski, Marisa C (2014) Quantification of electrophilic activation by hydrogen-bonding organocatalysts. J Am Chem Soc 136:16055-65
Peacock, Jacob R; Walvoord, Ryan R; Chang, Angela Y et al. (2014) Amino acid-dependent stability of the acyl linkage in aminoacyl-tRNA. RNA 20:758-64
Allen, Scott E; Hsieh, Sheng-Ying; Gutierrez, Osvaldo et al. (2014) Concerted amidation of activated esters: reaction path and origins of selectivity in the kinetic resolution of cyclic amines via N-heterocyclic carbenes and hydroxamic acid cocatalyzed acyl transfer. J Am Chem Soc 136:11783-91
Chen, Ming Z; Gutierrez, Osvaldo; Smith 3rd, Amos B (2014) Through-bond/through-space anion relay chemistry exploiting vinylepoxides as bifunctional linchpins. Angew Chem Int Ed Engl 53:1279-82
Walvoord, Ryan R; Kozlowski, Marisa C (2013) Minimizing the amount of nitromethane in palladium-catalyzed cross-coupling with aryl halides. J Org Chem 78:8859-64
Metz, Alison E; Kozlowski, Marisa C (2013) 2-Aryl-2-nitroacetates as central precursors to aryl nitromethanes, ýý-ketoesters, and ýý-amino acids. J Org Chem 78:717-22
Dickstein, Joshua S; Curto, John M; Gutierrez, Osvaldo et al. (2013) Mild aromatic palladium-catalyzed protodecarboxylation: kinetic assessment of the decarboxylative palladation and the protodepalladation steps. J Org Chem 78:4744-61
Padilla-Salinas, Rosaura; Walvoord, Ryan R; Tcyrulnikov, Sergei et al. (2013) Nitroethylation of vinyl triflates and bromides. Org Lett 15:3966-9

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