The objectives of this proposal are to make creative contributions to the total synthesis of naturally occurring substances possessing clinically significant biological activity. In addition, a number of new reactions are slated for development. The synthesis projects fall into two areas: Antitumor macrolides and polyether antibiotics. The antineoplastic macrolides which will be targets for asymmetric synthesis include both bryostatin and cytovaricin. The two ionophore projects will be concerned with the asymmetric syntheses of ferensimycin-B and lonomycin. New reactions slated for development will include hydroxyl-directed hydrogenations, hydrosilylations, and hydroborations. These reactions should contribute significantly to the development of new concepts and methodology in acyclic stereocontrol.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM033327-07
Application #
3282903
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1983-08-01
Project End
1991-11-30
Budget Start
1989-12-01
Budget End
1991-11-30
Support Year
7
Fiscal Year
1990
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
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; 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; 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

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