The major objective in this research is to make significant contributions to organic chemistry and medicine through synthetic studies on physiologically active natural and man-made organic compounds, including 1. the total synthesis and conformational analysis of the marine natural product palytoxin, 2. the synthesis and conformational analysis of oligosaccharides and their carbon analogues such as cellobiose, maltose, human blood group antigens, and sucrose, 3. the synthesis and conformational analysis of semi-synthetic polyether antibiotics, 4. the development of organic solvent soluble 310-helical oligopeptides, 5. semi- synthetic aequorins as a tool of the determination of local calcium concentration on the intact cells, and 6. enantioselective synthesis of saxitoxins and gonyautoxins. We believe that the power of organic chemistry is most effectively extended by challenging complex systems, and much of the progress of medicine critically depends upon the extension of the power of organic chemistry. It is also our specific objective to develop practical and efficient syntheses of certain natural products and their analogues which have high physiological activity, but are not available in appreciable amount from natural sources. These studies are again expected to stimulate the progress in medicine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS012108-17
Application #
3394718
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1978-06-01
Project End
1995-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
17
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Jensen, Erik A; Allen, Benjamin D; Kishi, Yoshito et al. (2008) Conformational analysis of a covalently cross-linked Watson-Crick base pair model. Bioorg Med Chem Lett 18:5884-7
Meppen, Malte; Wang, Yonghui; Cheon, Hwan-Sung et al. (2007) Synthetic 6-O-methylglucose-containing polysaccharides (sMGPs): design and synthesis. J Org Chem 72:1941-50
Hsu, Margaret C; Lee, Jinhwa; Kishi, Yoshito (2007) Synthetic 3-O-methylmannose-containing polysaccharides (sMMPs): design and synthesis. J Org Chem 72:1931-40
Wang, Yonghui; Ma, Jianguo; Cheon, Hwan-Sung et al. (2007) Aggregation behavior of tetraenoic fatty acids in aqueous solution. Angew Chem Int Ed Engl 46:1333-6
Hao, Junliang; Matsuura, Fumiyoshi; Kishi, Yoshito et al. (2006) Stereochemistry of pteriatoxins A, B, and C. J Am Chem Soc 128:7742-3
Matsuura, Fumiyoshi; Peters, Rene; Anada, Masahiro et al. (2006) Unified total synthesis of pteriatoxins and their diastereomers. J Am Chem Soc 128:7463-5
Matsuura, Fumiyoshi; Hao, Junliang; Reents, Reinhard et al. (2006) Total synthesis and stereochemistry of pinnatoxins B and C. Org Lett 8:3327-30
Ghosh, Indranath; Zeng, Hongbo; Kishi, Yoshito (2004) Application of chiral lanthanide shift reagents for assignment of absolute configuration of alcohols. Org Lett 6:4715-8
Adams, Christopher M; Ghosh, Indranath; Kishi, Yoshito (2004) Validation of lanthanide chiral shift reagents for determination of absolute configuration: total synthesis of glisoprenin A. Org Lett 6:4723-6
Ghosh, Indranath; Kishi, Yoshito; Tomoda, Hiroshi et al. (2004) Use of a chiral praseodymium shift reagent in predicting the complete stereostructure of glisoprenin A. Org Lett 6:4719-22

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