The goal of this research program is to develop and apply state-of-the-art computation methods to understand stereoselectivity and to aid in the design of new stereoselective reagents and catalysts. The control of stereoselectivity is an essential feature of efficient synthesis, and many elegant procedures for the control of stereochemistry have been developed. These are critical elements in the synthesis of effective pharmaceutical agents. This renewal of GM36700 is built on the achievements of the last grant period. Collaborations with many synthetic laboratories around the world have kept our attention focused on problems that are central to progress in organic synthesis. The grant has been a training vehicle for a large number of graduate students, postdocs, and visitors to our laboratories from synthetic groups, and these people have become leaders in computational understanding of organic and pharmaceutical chemistry.
The specific aims for the new grant period are:
Aim 1 : Development of quantum mechanical methods to provide accurate predictions of stereoselectivity for large and flexible molecules. Many advances in computational methods and applications are needed to make these practical for the real-time exploration of important organic reactions.
Aim 2 : Explorations of asymmetric organocatalysis and predictions and testing of new catalysts. Many organocatalysts have been discovered and will be studied theoretically. Newly designed catalysts will be studied by us or our collaborators.
Aim 3 : Exploration of transition metal catalyzed asymmetric reactions. Studies of Rh, Mo, Ru, Pd, and Ni-catalyzed hydrogenations, allylic substitutions, and asymmetric coupling reactions will increase knowledge of the origins of transition metal catalysis of stereoselective reactions.
Aim 4 : Collaborative design and testing of new reagents and catalysts for stereoselective reactions. Ongoing collaborations with many synthetic organic chemists and other collaborators likely to develop during the next grant period drive the development of new technology and the increase in understanding of stereoselectivity. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM036700-23
Application #
7354076
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Schwab, John M
Project Start
1998-09-01
Project End
2010-01-31
Budget Start
2008-02-01
Budget End
2009-01-31
Support Year
23
Fiscal Year
2008
Total Cost
$291,926
Indirect Cost
Name
University of California Los Angeles
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Lam, Yu-Hong; Grayson, Matthew N; Holland, Mareike C et al. (2016) Theory and Modeling of Asymmetric Catalytic Reactions. Acc Chem Res 49:750-62
Hie, Liana; Fine Nathel, Noah F; Hong, Xin et al. (2016) Nickel-Catalyzed Activation of Acyl C-O Bonds of Methyl Esters. Angew Chem Int Ed Engl 55:2810-4
Pham, Hung V; Karns, Alexander S; Vanderwal, Christopher D et al. (2015) Computational and experimental investigations of the formal dyotropic rearrangements of Himbert arene/allene cycloadducts. J Am Chem Soc 137:6956-64
Krenske, Elizabeth H; Houk, K N; Harmata, Michael (2015) Computational analysis of the stereochemical outcome in the imidazolidinone-catalyzed enantioselective (4 + 3)-cycloaddition reaction. J Org Chem 80:744-50
Hooper, Joel F; James, Natalie C; Bozkurt, Esra et al. (2015) Medium-Ring Effects on the Endo/Exo Selectivity of the Organocatalytic Intramolecular Diels-Alder Reaction. J Org Chem 80:12058-75
Hie, Liana; Fine Nathel, Noah F; Shah, Tejas K et al. (2015) Conversion of amides to esters by the nickel-catalysed activation of amide C-N bonds. Nature 524:79-83
Lam, Yu-Hong; Houk, K N (2015) Origins of stereoselectivity in intramolecular aldol reactions catalyzed by cinchona amines. J Am Chem Soc 137:2116-27
Patel, Ashay; Vella, Joseph R; Ma, Zhi-Xiong et al. (2015) Transition State Gauche Effects Control the Torquoselectivities of the Electrocyclizations of Chiral 1-Azatrienes. J Org Chem 80:11888-94
Noey, Elizabeth L; Tibrewal, Nidhi; Jiménez-Osés, Gonzalo et al. (2015) Origins of stereoselectivity in evolved ketoreductases. Proc Natl Acad Sci U S A 112:E7065-72
Krenske, Elizabeth H; Lam, Sarah; Ng, Jerome P L et al. (2015) Concerted Ring Opening and Cycloaddition of Chiral Epoxy Enolsilanes with Dienes. Angew Chem Int Ed Engl 54:7422-5

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