Studying the synthesis of natural products provides rich opportunities for identifying new directions in chemistry and biology. The overarching goal of our research program is to study the chemical synthesis of small molecules of medicinal relevance and to advance chemical technology for the next-generation of drug synthesis. Through this project, we will better understand how nature performs cycloaddition-type dimerization reactions to produce higher order pyrrole-imidazole alkaloids. We will test the biosynthetic hypotheses and develop biomimetic synthetic approaches to these natural products. Inspired by the oxidative metalloenzymes, we will further develop new catalyst systems for C-H and olefin oxidation. We will also study how cyclic dinucleotides mediate innate immune response. Our research will have direct impacts on the discovery and manufacturing of small-molecule drugs.

Public Health Relevance

This research project is directed toward advancing technologies for drug synthesis and providing insights into how biological systems function. We will develop new chemical methods to enable the efficient synthesis of small-molecule drugs. This project will also help improve our understanding of the biosynthetic machineries and immune systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM079554-07
Application #
8594253
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2007-01-01
Project End
2016-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
7
Fiscal Year
2014
Total Cost
$269,838
Indirect Cost
$98,838
Name
University of Texas Sw Medical Center Dallas
Department
Biochemistry
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Ma, Zhiqiang; You, Lin; Chen, Chuo (2017) Stereocontrolled Formation of a [4.4]Heterospiro Ring System with Unexpected Inversion of Configuration at the Spirocenter. J Org Chem 82:731-736
Han, Lei; Xia, Jibao; You, Lin et al. (2017) Ketone-catalyzed photochemical C(sp3)-H chlorination. Tetrahedron 73:3696-3701
Chen, Chuo (2016) The past, present, and future of the Yang reaction. Org Biomol Chem 14:8641-7
Ma, Zhiqiang; Wang, Xiao; Ma, Yuyong et al. (2016) Asymmetric Synthesis of Axinellamines A and B. Angew Chem Int Ed Engl 55:4763-6
Zhang, Chengwei; You, Lin; Chen, Chuo (2016) Palladium-Catalyzed C-H Arylation of 1,2,3-Triazoles. Molecules 21:
Shi, Heping; De, Saptarshi; Wang, Qiaoling et al. (2015) Construction of the 5,6,7-tricyclic skeleton of lancifodilactone F. Tetrahedron Lett 56:3225-3227
Ma, Yuyong; De, Saptarshi; Chen, Chuo (2015) Syntheses of Cyclic Guanidine-Containing Natural Products. Tetrahedron 71:1145-1173
Wang, Xiaolei; Chen, Chuo (2015) An approach for the synthesis of nakamuric acid. Tetrahedron 71:3690-3693
Ma, Zhiqiang; Wang, Xiaolei; Wang, Xiao et al. (2015) ORGANIC SYNTHESIS. Response to Comment on ""Asymmetric syntheses of sceptrin and massadine and evidence for biosynthetic enantiodivergence"". Science 349:149
Shi, Heping; Wu, Jiaxi; Chen, Zhijian J et al. (2015) Molecular basis for the specific recognition of the metazoan cyclic GMP-AMP by the innate immune adaptor protein STING. Proc Natl Acad Sci U S A 112:8947-52

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