Abstract

The major objective of this research is to make significant contributions to organic chemistry and medicine through synthetic studies of natural products with antitumor activity, including mitomycins, aclacinomycins, aplysiatoxins, macbecin, phyllanthocin, and bruceantin. We believe that the power of organic synthesis can be most effectively extended by challenging such complex synthetic targets. Much of the progress in medicine depends upon the extension of this power of organic chemistry. It is also our specific objective to develop general, efficient and practical syntheses of certain natural products which have promising antitumor activity but which are not available in appreciable amounts from natural sources, and then apply them to the synthesis of their analogs and derivatives with the hope that some will exhibit improved therapeutic ratios.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA022215-08
Application #
3165775
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1978-03-01
Project End
1986-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
8
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code

  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