Abstract

The major objective of this research is to make significant contributions to organic chemistry and medicine through synthetic studies of the natural products with antitumor activity, including the halichondrins, the spongistatins, and the mycolactones. We believe that the power of organic chemistry, especially organic synthesis, is most effectively extended by challenging complex systems, and much of the progress of medicine certainly depends upon the extension of the power of chemistry. More specifically, research efforts will be made first to develop general, flexible, and efficient syntheses of certain natural products and then to apply these to the synthesis of their analogs and derivatives. These studies will provide clues for developing better antitumor drugs and/or will help to deliver a new anticancer drug to patients at an acceptable cost. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA022215-31
Application #
7407550
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Lees, Robert G
Project Start
1978-03-17
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2010-04-30
Support Year
31
Fiscal Year
2008
Total Cost
$472,682
Indirect Cost

  Institution

Name
Harvard University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138

  Publications

Kishi, Yoshito (2011) Chemistry of mycolactones, the causative toxins of Buruli ulcer. Proc Natl Acad Sci U S A 108:6703-8
Spangenberg, Thomas; Kishi, Yoshito (2010) Highly sensitive, operationally simple, cost/time effective detection of the mycolactones from the human pathogen Mycobacterium ulcerans. Chem Commun (Camb) 46:1410-2
Spangenberg, Thomas; Aubry, Sylvain; Kishi, Yoshito (2010) Synthesis and structure assignment of the minor metabolite arising from the frog pathogen Mycobacterium liflandii. Tetrahedron Lett 51:1782-1785
Jackson, Katrina L; Li, Wenju; Chen, Chi-Li et al. (2010) Scalable and efficient synthesis of the mycolactone core. Tetrahedron 66:2263-2272
Kim, Dae-Shik; Dong, Cheng-Guo; Kim, Joseph T et al. (2009) New syntheses of E7389 C14-C35 and halichondrin C14-C38 building blocks: double-inversion approach. J Am Chem Soc 131:15636-41
Guo, Haibing; Dong, Cheng-Guo; Kim, Dae-Shik et al. (2009) Toolbox approach to the search for effective ligands for catalytic asymmetric Cr-mediated coupling reactions. J Am Chem Soc 131:15387-93
Yang, Yu-Rong; Kim, Dae-Shik; Kishi, Yoshito (2009) Second generation synthesis of C27-C35 building block of E7389, a synthetic halichondrin analogue. Org Lett 11:4516-9
Dong, Cheng-Guo; Henderson, James A; Kaburagi, Yosuke et al. (2009) New syntheses of E7389 C14-C35 and halichondrin C14-C38 building blocks: reductive cyclization and oxy-Michael cyclization approaches. J Am Chem Soc 131:15642-6
Kim, Han-Je; Jackson, Katrina L; Kishi, Yoshito et al. (2009) Heterogeneity in the stereochemistry of mycolactones isolated from M. marinum: toxins produced by fresh vs. saltwater fish pathogens. Chem Commun (Camb) :7402-4
Liu, Xiang; Henderson, James A; Sasaki, Takeo et al. (2009) Dramatic improvement in catalyst loadings and molar ratios of coupling partners for Ni/Cr-mediated coupling reactions: heterobimetallic catalysts. J Am Chem Soc 131:16678-80

Showing the most recent 10 out of 36 publications