Abstract

The enantioselective total syntheses of two biologically significant natural products, azaspiracid and amphidinolide B1, are detailed in this proposal. The azaspiracids have been shown to possess considerable toxicity in mice. During the course of this project, the absolute stereochemical assignments of azaspiracid will be proven by total synthesis. In addition, the stereochemical correlation between the C1-C25 and the C26-C47 regions of azaspiracid will be established. The amphidinolides have been shown to be potent cytotoxic agents against several cancer cell lines. Several novel methodologies will be introduced during the course of the total syntheses. These methods will include a domino [3+2] cycloaddition, tandem SO2 extrusion/Cope rearrangement, and asymmetric selenide oxidation with in situ [2,3] sigmatropic rearrangement in order to introduce key functionalities.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM063723-04
Application #
6747837
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
2002-06-01
Project End
2007-05-31
Budget Start
2004-06-01
Budget End
2005-05-31
Support Year
4
Fiscal Year
2004
Total Cost
$220,519
Indirect Cost

  Institution

Name
Oregon State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
053599908
City
Corvallis
State
OR
Country
United States
Zip Code
97339

  Publications

Mahapatra, Subham; Carter, Rich G (2013) Exploiting hidden symmetry in natural products: total syntheses of amphidinolides C and F. J Am Chem Soc 135:10792-803
Saha, Mrinmoy; Carter, Rich G (2013) Toward a unified approach for the lycopodines: synthesis of 10-hydroxylycopodine, deacetylpaniculine, and paniculine. Org Lett 15:736-9
Veerasamy, Nagarathanam; Carlson, Erik C; Collett, Nathan D et al. (2013) Enantioselective approach to quinolizidines: total synthesis of cermizine D and formal syntheses of senepodine G and cermizine C. J Org Chem 78:4779-800
Lu, Liang; Zhang, Wei; Nam, Sangkil et al. (2013) Amphidinolide B: total synthesis, structural investigation, and biological evaluation. J Org Chem 78:2213-47
Mahapatra, Subham; Carter, Rich G (2012) Enantioselective total synthesis of amphidinolide F. Angew Chem Int Ed Engl 51:7948-51
Veerasamy, Nagarathanam; Carlson, Erik C; Carter, Rich G (2012) Expedient enantioselective synthesis of cermizine D. Org Lett 14:1596-9
Collett, Nathan D; Carter, Rich G (2011) Stereoselective synthesis of the eastern quinolizidine portion of himeradine A. Org Lett 13:4144-7
Yang, Hua; Carter, Rich G (2010) Proline Sulfonamide-Based Organocatalysis: Better Late than Never. Synlett 2010:2827-2838
Yang, Hua; Carter, Rich G (2010) Development of an enantioselective route toward the Lycopodium alkaloids: total synthesis of lycopodine. J Org Chem 75:4929-38
Yang, Hua; Mahapatra, Subham; Cheong, Paul Ha-Yeon et al. (2010) Highly stereoselective and scalable anti-aldol reactions using N-(p-dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide: scope and origins of stereoselectivities. J Org Chem 75:7279-90

Showing the most recent 10 out of 24 publications