The goal of this program is to define new strategies and methods for the synthesis of bioactive molecules. The small molecules that we construct can provide tools to study biological processes and may ultimately be used to develop new therapeutics. These studies will also lead to a better understanding of organic functional group reactivity. Specifically, we intend to develop a general strategy for the synthesis of the sesterterpene compounds neomangicol C and mangicol A. These compounds possess antitumor, antibacterial and anti-inflammatory properties. We also present a novel iodine-mediated pentannulation reaction that will be applied to the synthesis of a series of resveratrol-derived natural products. It is our anticipation that these new methodological developments for pentannulation will streamline the synthesis of complex molecules. The total synthesis of the natural products drives the development of new methods and strategies. In turn, these new developments will be applied to the synthesis of other molecules of biological and structural interest. These contributions will aid advances in human medicine and chemical biology by providing a synthesis foundation.

Public Health Relevance

Finding new and more efficient ways to construct small molecules is an important pursuit that will provide new tools for chemical biology and medicine and lead to improvements in human health. Our goals are to develop new strategies and methods that efficiently build small molecules that are of pharmaceutical importance and natural products. In this regard, we are especially interested in new five-membered ring forming reactions using transition metals.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM084906-05
Application #
8267680
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2008-08-01
Project End
2013-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$281,360
Indirect Cost
$85,340
Name
University of California Berkeley
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Kou, Kevin G M; Li, Beryl X; Lee, Jack C et al. (2016) Syntheses of Denudatine Diterpenoid Alkaloids: Cochlearenine, N-Ethyl-1α-hydroxy-17-veratroyldictyzine, and Paniculamine. J Am Chem Soc 138:10830-3
Weber, Manuel; Owens, Kyle; Sarpong, Richmond (2015) Atropurpuran - Missing Biosynthetic Link Leading to the Hetidine and Arcutine C20-Diterpenoid Alkaloids or an Oxidative Degradation Product? Tetrahedron Lett 56:3600-3603
Marth, C J; Gallego, G M; Lee, J C et al. (2015) Network-analysis-guided synthesis of weisaconitine D and liljestrandinine. Nature 528:493-8
Schultz, Erica E; Lindsay, Vincent N G; Sarpong, Richmond (2014) Expedient synthesis of fused azepine derivatives using a sequential rhodium(II)-catalyzed cyclopropanation/1-aza-Cope rearrangement of dienyltriazoles. Angew Chem Int Ed Engl 53:9904-8
Heller, Stephen T; Kiho, Toshihiro; Narayan, Alison R H et al. (2013) Protic-solvent-mediated cycloisomerization of quinoline and isoquinoline propargylic alcohols: syntheses of (±)-3-demethoxyerythratidinone and (±)-cocculidine. Angew Chem Int Ed Engl 52:11129-33
de Jesus Cortez, Felipe; Lapointe, David; Hamlin, Amy M et al. (2013) Synthetic studies on the icetexones: enantioselective formal syntheses of icetexone and epi-icetexone. Tetrahedron 69:
Lebold, Terry P; Wood, Jessica L; Deitch, Josh et al. (2013) A divergent approach to the synthesis of the yohimbinoid alkaloids venenatine and alstovenine. Nat Chem 5:126-31
Hamlin, Amy M; Cortez, Felipe de Jesus; Lapointe, David et al. (2013) Gallium(III)-catalyzed cycloisomerization approach to the diterpenoid alkaloids: construction of the core structure for the hetidines and hetisines. Angew Chem Int Ed Engl 52:4854-7
Isaacs, André K; Qi, Suzhen; Sarpong, Richmond et al. (2012) Insect ryanodine receptor: distinct but coupled insecticide binding sites for [N-C(3)H(3)]chlorantraniliprole, flubendiamide, and [(3)H]ryanodine. Chem Res Toxicol 25:1571-3
Schultz, Erica E; Pujanauski, Brian G; Sarpong, Richmond (2012) Synthetic studies toward lapidilectine-type Kopsia alkaloids. Org Lett 14:648-51

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