Abstract

We propose to synthesize members of four classes of biologically important natural products: the macrocyclic rifamycins, streptovaricins, and polyene macrolides, as well as related compounds such as tirandamycin. These materials exhibit significant antitumor, antibiotic, and antifungal properties, and provide a continuing challenge to the synthetic chemist. In the preceding grant period, we developed a number of versatile methods for acyclic stereocontrol with relative asymmetric induction, based on the functionalization of olefins via cyclic intermediates. We intend to employ these methods in the syntheses proposed, as well as to develop a number of new ones.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM030759-11
Application #
3278632
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1977-09-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
11
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704

  Publications

Hammond, Ming C; Bartlett, Paul A (2007) Synthesis of amino acid-derived cyclic acyl amidines for use in beta-strand peptidomimetics. J Org Chem 72:3104-7
Phillips, Scott T; Blasdel, Landy K; Bartlett, Paul A (2005) @-tides as reporters for molecular associations. J Am Chem Soc 127:4193-8
Hansen, Kristina K; Grosch, Benjamin; Greiveldinger-Poenaru, Sorana et al. (2003) Synthesis and evaluation of macrocyclic transition state analogue inhibitors for alpha-chymotrypsin. J Org Chem 68:8465-70
Hansen, Kristina K; Hansen, Henrik C; Clark, Ryan C et al. (2003) Identification of novel macrocyclic peptidase substrates via on-bead enzymatic cyclization. J Org Chem 68:8459-64
Lewis, Jason G; Bartlett, Paul A (2003) Amino acid-derived heterocycles as combinatorial library targets: bicyclic aminal lactones. J Comb Chem 5:278-84
Trump, Ryan P; Bartlett, Paul A (2003) Amino acid-derived heterocycles as combinatorial library targets: spirocyclic ketal lactones. J Comb Chem 5:285-91
Todd, Matthew H; Ndubaku, Chudi; Bartlett, Paul A (2002) Amino acid derived heterocycles: lewis acid catalyzed and radical cyclizations from peptide acetals. J Org Chem 67:3985-8
Spaller, Mark R; Thielemann, Wolfgang T; Brennan, Paul E et al. (2002) Combinatorial synthetic design. Solution and polymer-supported synthesis of heterocycles via intramolecular aza Diels-Alder and imino alcohol cyclizations. J Comb Chem 4:516-22
Bartlett, Paul A; Yusuff, Naeem; Rico, Alice C et al. (2002) Antihydrophobic solvent effects: an experimental probe for the hydrophobic contribution to enzyme-inhibitor binding. J Am Chem Soc 124:3853-7
An, M; Toochinda, T; Bartlett, P A (2001) Five-membered ring analogues of shikimic acid. J Org Chem 66:1326-33

Showing the most recent 10 out of 13 publications