Abstract

The objectives of this proposed research are to make creative contributions to the total synthesis of naturally occurring substances possessing clinically significant biological activity. The present grant will continue to address the development of new stereoselective reactions and the application of this methodology to the asymmetric synthesis of ionophore and macrolide antibiotics and antineoplastic agents. The methodological studies dealing with new reaction discovery will emphasize the development of new reactions for controlling the stereochemical course of chemical processes. In the present study we will continue to focus our attention on """"""""directable"""""""" chemical processes. These studies will focus on the continued development of an iridium-catalyzed directable hydroboration process, the development of a directable Meerwein-Ponndorff-Verley reduction based on samarium diiodide, and the application of intramolecular variants of the Tishchenko reaction for long-range directed reductions of ketones. The targets for total synthesis will include the development of asymmetric syntheses of the antineoplastic agents bryostatin, calyculin, macbecin, and herbimycin, the ionophore antibiotic lonomycin, and the oligomycin macrolide rutamycin.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033327-09
Application #
3282904
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1983-08-01
Project End
1995-11-30
Budget Start
1992-12-01
Budget End
1993-11-30
Support Year
9
Fiscal Year
1993
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
02138

  Publications

Evans, David A; Nagorny, Pavel; McRae, Kenneth J et al. (2007) Enantioselective synthesis of oasomycin a, part I: synthesis of the C1-C12 and C13-C28 subunits. Angew Chem Int Ed Engl 46:537-40
Scheerer, Jonathan R; Lawrence, Jonathan F; Wang, Grace C et al. (2007) Asymmetric synthesis of salvinorin A, a potent kappa opioid receptor agonist. J Am Chem Soc 129:8968-9
Evans, David A; Nagorny, Pavel; McRae, Kenneth J et al. (2007) Enantioselective synthesis of oasomycin A, part III: fragment assembly and confirmation of structure. Angew Chem Int Ed Engl 46:545-8
Evans, David A; Nagorny, Pavel; Reynolds, Dominic J et al. (2007) Enantioselective synthesis of oasomycin A, part II: synthesis of the C29-C46 subunit. Angew Chem Int Ed Engl 46:541-4
Evans, David A; Nagorny, Pavel; Xu, Risheng (2006) Ceric ammonium nitrate promoted oxidation of oxazoles. Org Lett 8:5669-71
Evans, David A; Glorius, Frank; Burch, Jason D (2005) Complex aldol reactions for the construction of dense polyol stereoarrays: synthesis of the C33-C36 region of aflastatin A. Org Lett 7:3331-3
Evans, David A; Trenkle, William C; Zhang, Jing et al. (2005) Synthesis and confirmation of the absolute stereochemistry of the (-)-aflastatin a C9-C27 degradation polyol. Org Lett 7:3335-8
Evans, David A; Siska, Sarah J; Cee, Victor J (2003) Resurrecting the Cornforth model for carbonyl addition: studies on the origin of 1,2-asymmetric induction in enolate additions to heteroatom-substituted aldehydes. Angew Chem Int Ed Engl 42:1761-5
Evans, David A; Rajapakse, Hemaka A; Chiu, Anna et al. (2002) Asymmetric syntheses of pectenotoxins-4 and -8, part II: synthesis of the C20-C30 and C31-C40 subunits and fragment assembly. Angew Chem Int Ed Engl 41:4573-6
Evans, David A; Starr, Jeremy T (2002) A cascade cycloaddition strategy leading to the total synthesis of (-)-FR182877. Angew Chem Int Ed Engl 41:1787-90

Showing the most recent 10 out of 15 publications