Abstract

The aim of this program is to demonstrate the applicability and development of new synthetic principles and reactions to problems in organic chemistry related to chemotherapeutically important compounds. The new routes developed will lead to practical approaches to macrocycles, prostanoids, steroids, Beta-lactam antibiotics, and related systems. The use of transition metal templates as the """"""""chemist's enzymes"""""""" to exercise chemoselectivity, regioselectivity, and stereocontrol in an absolute and relative sense constitutes a major aspect of this proposal. Macrolides include the broad spectrum antibiotics related to the erythromycins and the polyene antifungal compounds of the amphotericin type. An all carbon macrocycle that possesses antitumor activity is represented by aspochalasin. Chiral synthesis and creation of stereochemistry in conformationally non-rigid systems (ie. acyclic ones) represent major aspects of the proposed strategies to prostanoids (of broad clinical application) and Vitamin D metabolites, of potential use in osteoporosis. New bond forming reactions will also address problems in picrotoxins, neurotransmitter inhibitors, and broad spectrum Beta-lactam antibiotics.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM013598-20
Application #
3268509
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1978-06-01
Project End
1988-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
20
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Trost, Barry M; Yang, Hanbiao; Dong, Guangbin (2011) Total syntheses of bryostatins: synthesis of two ring-expanded bryostatin analogues and the development of a new-generation strategy to access the C7-C27 fragment. Chemistry 17:9789-805
Trost, Barry M; Silverman, Steven M; Stambuli, James P (2011) Development of an asymmetric trimethylenemethane cycloaddition reaction: application in the enantioselective synthesis of highly substituted carbocycles. J Am Chem Soc 133:19483-97
Trost, Barry M; Gutierrez, Alicia C; Ferreira, Eric M (2010) Differential reactivities of enyne substrates in ruthenium- and palladium-catalyzed cycloisomerizations. J Am Chem Soc 132:9206-18
Trost, Barry M; O'Boyle, Brendan M; Hund, Daniel (2010) Investigation of a domino Heck reaction for the rapid synthesis of bicyclic natural products. Chemistry 16:9772-6
Trost, Barry M; Brindle, Cheyenne S (2010) The direct catalytic asymmetric aldol reaction. Chem Soc Rev 39:1600-32
Trost, Barry M; Dong, Guangbin (2010) Total synthesis of bryostatin 16 using a Pd-catalyzed diyne coupling as macrocyclization method and synthesis of C20-epi-bryostatin 7 as a potent anticancer agent. J Am Chem Soc 132:16403-16
Trost, Barry M; Zhang, Yong; Zhang, Ting (2009) Direct N-carbamoylation of 3-monosubstituted oxindoles with alkyl imidazole carboxylates. J Org Chem 74:5115-7
Trost, Barry M; Malhotra, Sushant; Olson, David E et al. (2009) Asymmetric synthesis of diamine derivatives via sequential palladium and rhodium catalysis. J Am Chem Soc 131:4190-1
Trost, Barry M; O'Boyle, Brendan M; Hund, Daniel (2009) Total synthesis and stereochemical assignment of (-)-ushikulide A. J Am Chem Soc 131:15061-74
Trost, Barry M; Hitce, Julien (2009) Direct asymmetric Michael addition to nitroalkenes: vinylogous nucleophilicity under dinuclear zinc catalysis. J Am Chem Soc 131:4572-3

Showing the most recent 10 out of 56 publications