Abstract

The basic objectives of this proposal are to make creative contributions to the total synthesis of naturally occurring substances possessing clinically significant biological activity. Targets for total synthesis include the potent antibiotics naphthyridinomycin, saframycin, macbecin, rosaramycin, josamycin, tylosin, and the Beta-lactams thienamycin and aphalosporin. Recently developed chiral enolate technology will be applied to enantioselective approaches to the construction of many of the listed target structures. Naphthyridinomycin, saframycin and macbecin all exhibit significant antitumor activity and rosaramycin (and related macrolides) and thienamycin are clinically valuable broad-spectrum antibiotics which are active against both gram-positive and gram-negative bacteria.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033328-03
Application #
3282906
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1983-08-01
Project End
1986-06-30
Budget Start
1985-04-01
Budget End
1986-06-30
Support Year
3
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

Bonazzi, Simone; Cheng, Bichu; Wzorek, Joseph S et al. (2013) Total synthesis of (-)-nakadomarin A. J Am Chem Soc 135:9338-41
Wzorek, Joseph S; Knopfel, Thomas F; Sapountzis, Ioannis et al. (2012) A macrocyclic approach to tetracycline natural products. Investigation of transannular alkylations and Michael additions. Org Lett 14:5840-3
Evans, David A; Adams, Drew J; Kwan, Eugene E (2012) Progress toward the syntheses of (+)-GB 13, (+)-himgaline, and himandridine. new insights into intramolecular imine/enamine aldol cyclizations. J Am Chem Soc 134:8162-70
Marcoux, David; Bindschädler, Pascal; Speed, Alexander W H et al. (2011) Effect of counterion structure on rates and diastereoselectivities in ?,?-unsaturated iminium-ion Diels-Alder reactions. Org Lett 13:3758-61
Evans, David A; Welch, Dennie S; Speed, Alexander W H et al. (2009) An aldol-based synthesis of (+)-peloruside a, a potent microtubule stabilizing agent. J Am Chem Soc 131:3840-1
Evans, David A; Kvaerno, Lisbet; Dunn, Travis B et al. (2008) Total synthesis of (+)-azaspiracid-1. An exhibition of the intricacies of complex molecule synthesis. J Am Chem Soc 130:16295-309
Evans, David A; Dunn, Travis B; Kvaerno, Lisbet et al. (2007) Total synthesis of (+)-azaspiracid-1. Part II: synthesis of the EFGHI sulfone and completion of the synthesis. Angew Chem Int Ed Engl 46:4698-703
Evans, David A; Mito, Shizue; Seidel, Daniel (2007) Scope and mechanism of enantioselective Michael additions of 1,3-dicarbonyl compounds to nitroalkenes catalyzed by nickel(II)-diamine complexes. J Am Chem Soc 129:11583-92
Evans, David A; Kvaerno, Lisbet; Mulder, Jason A et al. (2007) Total synthesis of (+)-azaspiracid-1. Part I: Synthesis of the fully elaborated ABCD aldehyde. Angew Chem Int Ed Engl 46:4693-7
Evans, David A; Fandrick, Keith R; Song, Hyun-Ji et al. (2007) Enantioselective Friedel-Crafts alkylations catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes. J Am Chem Soc 129:10029-41

Showing the most recent 10 out of 37 publications