Abstract

The proposed program focuses on synthesis of such complex natural products and their analogs by mimicking biological oxidative systems. Methods to form C-C bonds via oxidative C-H bond activation while establishing axial chirality will be developed using chiral oxidative catalysts. The possibility of selectivity in these transformations with respect to complex substrates is of significant synthetic potential. If such goals are realized, novel and unique synthetic strategies for the assembly of natural products can be envisioned. Routes to chiral binaphthyls, perylenequinones, bisanthraquinones, hypericins, and bioxanthracenes will be developed. The potential for photodynamic cancer therapy with the perylenequinone and hypericin structural types is especially noteworthy given recent developments in this area.

Public Health Relevance

Small molecules will be synthesized for examination as anticancer therapeutics. In addition, the underlying chemical synthetic technology that is developed will be broadly useful in other contexts thereby facilitating the discovery and generation of new pharmaceutical agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56CA109164-05A1
Application #
7870549
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Lees, Robert G
Project Start
2004-07-20
Project End
2010-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
5
Fiscal Year
2009
Total Cost
$197,944
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

(2014) Correction to Aerobic Copper-Catalyzed Organic Reactions. Chem Rev 114:899
Dickstein, Joshua S; Curto, John M; Gutierrez, Osvaldo et al. (2013) Mild aromatic palladium-catalyzed protodecarboxylation: kinetic assessment of the decarboxylative palladation and the protodepalladation steps. J Org Chem 78:4744-61
Allen, Scott E; Walvoord, Ryan R; Padilla-Salinas, Rosaura et al. (2013) Aerobic copper-catalyzed organic reactions. Chem Rev 113:6234-458
Mulrooey, Carol A; O'Brien, Erin M; Morgan, Barbara J et al. (2012) Perylenequinones: Isolation, Synthesis, and Biological Activity. European J Org Chem 2012:3887-3904
Morgan, Barbara J; Mulrooney, Carol A; Kozlowski, Marisa C (2010) Perylenequinone natural products: evolution of the total synthesis of cercosporin. J Org Chem 75:44-56
O'Brien, Erin M; Li, Jingxian; Carroll, Patrick J et al. (2010) Synthesis of the cores of hypocrellin and shiraiachrome: diastereoselective 1,8-diketone aldol cyclization. J Org Chem 75:69-73
O'Brien, Erin M; Morgan, Barbara J; Mulrooney, Carol A et al. (2010) Perylenequinone natural products: total synthesis of hypocrellin A. J Org Chem 75:57-68
Morgan, Barbara J; Mulrooney, Carol A; O'Brien, Erin M et al. (2010) Perylenequinone natural products: total syntheses of the diastereomers (+)-phleichrome and (+)-calphostin D by assembly of centrochiral and axial chiral fragments. J Org Chem 75:30-43
Mulrooney, Carol A; Morgan, Barbara J; Li, Xiaolin et al. (2010) Perylenequinone natural products: enantioselective synthesis of the oxidized pentacyclic core. J Org Chem 75:16-29
Morgan, Barbara J; Dey, Sangeeta; Johnson, Steven W et al. (2009) Design, synthesis, and investigation of protein kinase C inhibitors: total syntheses of (+)-calphostin D, (+)-phleichrome, cercosporin, and new photoactive perylenequinones. J Am Chem Soc 131:9413-25

Showing the most recent 10 out of 11 publications