The long-term objectives of this program include the laboratory synthesis of complex natural products possessing desirable biological activity as well as the development of new synthetic methodology which will simplify this task. Specific natural products to be studied include the promising antitumor agent rhizoxin, structurally simplified analogues of rhizoxin, and the highly cytotoxic marine natural product swinholide, as well as nisakinolide, and scytophycin C, both of which are structurally very similar to swinholide. The main thrust of the program is to develop new catalytic procedures for carbon-carbon bond formation using chiral Lewis acids to promote the union of two pi systems. Two new vicinal sp3 carbon centers can be generated in such reactions, and the aim is to control stereochemistry at these sites in both a relative and absolute sense. Specific examples which will be studied represent reactions between aldehydes and allylstannanes or allylsilanes spanning a wide range of structural types; these reactions represent catalytic alternatives to the most powerful enantioselective synthetic reactions presently available.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028961-16
Application #
2391891
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1981-06-01
Project End
1998-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
16
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Utah
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Petersen, Mark E; Kedei, Noemi; Lewin, Nancy E et al. (2016) Replacement of the Bryostatin A- and B-Pyran Rings With Phenyl Rings Leads to Loss of High Affinity Binding With PKC. Tetrahedron Lett 57:4749-4753
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Keck, Gary E; Poudel, Yam B; Rudra, Arnab et al. (2012) Role of the C8 gem-dimethyl group of bryostatin 1 on its unique pattern of biological activity. Bioorg Med Chem Lett 22:4084-8
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Kedei, Noemi; Telek, Andrea; Czap, Alexandra et al. (2011) The synthetic bryostatin analog Merle 23 dissects distinct mechanisms of bryostatin activity in the LNCaP human prostate cancer cell line. Biochem Pharmacol 81:1296-308
Keck, Gary E; Poudel, Yam B; Rudra, Arnab et al. (2010) Molecular modeling, total synthesis, and biological evaluations of C9-deoxy bryostatin 1. Angew Chem Int Ed Engl 49:4580-4

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