Based on our continued development of powerful and rapid methodology for the study of reaction mechanisms, we propose to study the mechanisms for a series of important organic, organometallic, and bioorganic reactions. This includes coarctate reactions, conjugate additions to cuprates, olefin metathesis, additions of ketenes and phosphinidenes to alkenes, the enzymatic decarboxylation of orotate, the enzymatic cyclization of squalene oxide, and many others. The unique capabilities of our methodologies should significantly advance mechanistic understanding of these reactions. We also plan to extend our methodology by developing more robust probes of reaction mechanisms and isotope-effect probes of structure and intermolecular interactions. The health-relatedness of this work derives from its impact on the understanding of reactions important in the synthesis of medicinally important substances and reactions important in biosynthetic pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM045617-11
Application #
6386164
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
1991-01-01
Project End
2003-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
11
Fiscal Year
2001
Total Cost
$195,550
Indirect Cost
Name
Texas A&M University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
047006379
City
College Station
State
TX
Country
United States
Zip Code
77845
Kurouchi, Hiroaki; Singleton, Daniel A (2018) Labelling and determination of the energy in reactive intermediates in solution enabled by energy-dependent reaction selectivity. Nat Chem 10:237-241
Bailey, Johnathan O; Singleton, Daniel A (2017) Failure and Redemption of Statistical and Nonstatistical Rate Theories in the Hydroboration of Alkenes. J Am Chem Soc 139:15710-15723
Issaian, Adena; Faizi, Darius J; Bailey, Johnathan O et al. (2017) Mechanistic Studies of Formal Thioboration Reactions of Alkynes. J Org Chem 82:8165-8178
Aziz, Hannah R; Singleton, Daniel A (2017) Concert along the Edge: Dynamics and the Nature of the Border between General and Specific Acid-Base Catalysis. J Am Chem Soc 139:5965-5972
Kurouchi, Hiroaki; Andujar-De Sanctis, Ivonne L; Singleton, Daniel A (2016) Controlling Selectivity by Controlling Energy Partitioning in a Thermal Reaction in Solution. J Am Chem Soc 138:14534-14537
Patel, Ashay; Chen, Zhuo; Yang, Zhongyue et al. (2016) Dynamically Complex [6+4] and [4+2] Cycloadditions in the Biosynthesis of Spinosyn A. J Am Chem Soc 138:3631-4
Nieves-Quinones, Yexenia; Singleton, Daniel A (2016) Dynamics and the Regiochemistry of Nitration of Toluene. J Am Chem Soc 138:15167-15176
Biswas, Bibaswan; Singleton, Daniel A (2015) Controlling Selectivity by Controlling the Path of Trajectories. J Am Chem Soc 137:14244-7
Plata, R Erik; Singleton, Daniel A (2015) A case study of the mechanism of alcohol-mediated Morita Baylis-Hillman reactions. The importance of experimental observations. J Am Chem Soc 137:3811-26
Andujar-De Sanctis, Ivonne L; Singleton, Daniel A (2012) Racing carbon atoms. Atomic motion reaction coordinates and structural effects on Newtonian kinetic isotope effects. Org Lett 14:5238-41

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