Abstract

The goal of this program is to develop new strategies for the synthesis of bioactive molecules in the prenylated indole alkaloid family. The complex natural products that we construct, and their unique derivatives which are only accessible using our strategies, will provide small molecules that will serve as a starting point to identify anticancer compounds that function via novel mechanisms. Our synthetic studies should also lead to insights into the biosynthesis of a subset of the prenylated indole alkaloids for which the biogenesis is not established. Specifically, we intend to develop strategies to synthesize different structural classes of prenylated indole alkaloids including the citrinalins, cyclopiamine, citrinadins and the stephacidins.

Public Health Relevance

Finding new and more efficient ways to synthesize complex small molecules derived from natural products is an important pursuit that may lead to improvements in human health, especially the identification of new anticancer compounds. Our goals are to develop new strategies to efficiently construct complex natural products in the prenylated indole alkaloid family and their associated derivatives. These small molecules will positively address the treatment of cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM086374-06
Application #
9054864
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lees, Robert G
Project Start
2009-09-30
Project End
2019-01-31
Budget Start
2016-02-01
Budget End
2017-01-31
Support Year
6
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

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

  Publications

Roque, Jose B; Kuroda, Yusuke; Göttemann, Lucas T et al. (2018) Deconstructive diversification of cyclic amines. Nature 564:244-248
Doering, Nicolle A; Kou, Kevin G M; Norseeda, Krissada et al. (2018) A Copper-Mediated Conjugate Addition Approach to Analogues of Aconitine-Type Diterpenoid Alkaloids. J Org Chem 83:12911-12920
Roque, Jose B; Kuroda, Yusuke; Göttemann, Lucas T et al. (2018) Deconstructive fluorination of cyclic amines by carbon-carbon cleavage. Science 361:171-174
Mukai, Ken; de Sant'Ana, Danilo Pereira; Hirooka, Yasuo et al. (2018) Bioinspired chemical synthesis of monomeric and dimeric stephacidin A congeners. Nat Chem 10:38-44
Lindsay, Vincent N G; Murphy, Rebecca A; Sarpong, Richmond (2017) Effect of protic additives in Cu-catalysed asymmetric Diels-Alder cycloadditions of doubly activated dienophiles: towards the synthesis of magellanine-type Lycopodium alkaloids. Chem Commun (Camb) 53:10291-10294
Fraley, Amy E; Garcia-Borràs, Marc; Tripathi, Ashootosh et al. (2017) Function and Structure of MalA/MalA', Iterative Halogenases for Late-Stage C-H Functionalization of Indole Alkaloids. J Am Chem Soc 139:12060-12068
Finkbeiner, Peter; Murai, Kenichi; Röpke, Michael et al. (2017) Total Synthesis of Terpenoids Employing a ""Benzannulation of Carvone"" Strategy: Synthesis of (-)-Crotogoudin. J Am Chem Soc 139:11349-11352
de Rond, Tristan; Stow, Parker; Eigl, Ian et al. (2017) Oxidative cyclization of prodigiosin by an alkylglycerol monooxygenase-like enzyme. Nat Chem Biol 13:1155-1157
Mercado-Marin, Eduardo V; Sarpong, Richmond (2015) Unified Approach to Prenylated Indole Alkaloids: Total Syntheses of (-)-17-Hydroxy-Citrinalin B, (+)-Stephacidin A, and (+)-Notoamide I. Chem Sci 6:5048-5052
Beng, Timothy K; Takeuchi, Hironori; Weber, Manuel et al. (2015) Stereocontrolled synthesis of vicinally functionalized piperidines by nucleophilic ?-addition of alkyllithiums to ?-aryl substituted piperidine enecarbamates. Chem Commun (Camb) 51:7653-6

Showing the most recent 10 out of 22 publications