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
Zhu, Chen; Xia, Ji-Bao; Chen, Chuo (2014) Vanadium-catalyzed oxidative Strecker reaction: ?-C-H cyanation of para-methoxyphenyl (PMP)-protected primary amines. Tetrahedron Lett 55:
Wang, Xiao; Ma, Zhiqiang; Wang, Xiaolei et al. (2014) Dimeric pyrrole-imidazole alkaloids: synthetic approaches and biosynthetic hypotheses. Chem Commun (Camb) 50:8628-39
Xia, Ji-Bao; Ma, Yuyong; Chen, Chuo (2014) Vanadium-Catalyzed C(sp(3))-H Fluorination Reactions. Org Chem Front 1:468-472
Xia, Ji-Bao; Zhu, Chen; Chen, Chuo (2014) Visible light-promoted metal-free sp(3)-C-H fluorination. Chem Commun (Camb) 50:11701-4
Ma, Zhiqiang; Wang, Xiaolei; Wang, Xiao et al. (2014) Asymmetric syntheses of sceptrin and massadine and evidence for biosynthetic enantiodivergence. Science 346:219-24
Zhu, Chen; Xia, Ji-Bao; Chen, Chuo (2014) A simple method for the electrophilic cyanation of secondary amines. Org Lett 16:247-9
Wu, Jiaxi; Sun, Lijun; Chen, Xiang et al. (2013) Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339:826-30
Zhang, Xu; Shi, Heping; Wu, Jiaxi et al. (2013) Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol Cell 51:226-35
Wang, Xiao; Wang, Xiaolei; Tan, Xianghui et al. (2013) Correction to a biomimetic route for construction of the [4 + 2] and [3 + 2] core skeletons of dimeric pyrrole-imidazole alkaloids and asymmetric synthesis of ageliferins. J Am Chem Soc 135:1163
Xia, Ji-Bao; Zhu, Chen; Chen, Chuo (2013) Visible light-promoted metal-free C-H activation: diarylketone-catalyzed selective benzylic mono- and difluorination. J Am Chem Soc 135:17494-500

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