Abstract

It is proposed to synthesize and study natural and nonnatural members of a class of compounds capable of forming biradicals under physiological conditions with the tandem goals (1) to increase our understanding of the detailed mechanisms by which these substances cleave DNA and function as antitumor agents; and (2) to provide by chemical synthesis new structures for study as potential DNA cleaving agents and as leads for the design of new antitumor agents. This is a multifaceted program which is composed of the following subdivisions: (a) Synthesis of Neocarzinostatin Chromophore, its Aglycone, and Nonnatural Derivatives of the Chromophore Core; (b) Synthesis and Study of Dynemicin and Related Structures; (c) Design and Synthesis of Nonnatural DNA Cleaving Agents; (d) Mechanistic Studies of Natural and Nonnatural DNA Cleaving Agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
2R37CA047148-11
Application #
2729413
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Beisler, John A
Project Start
1988-04-01
Project End
1998-07-31
Budget Start
1998-02-01
Budget End
1998-07-31
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
California Institute of Technology
Department
Type
Schools of Engineering
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125

  Publications

Andresen, Vibeke; Erikstein, Bjarte S; Mukherjee, Herschel et al. (2016) Anti-proliferative activity of the NPM1 interacting natural product avrainvillamide in acute myeloid leukemia. Cell Death Dis 7:e2497
Blasdel, Landy K; Lee, DongEun; Sun, Binyuan et al. (2013) (S)-4-Trimethylsilyl-3-butyn-2-ol as an auxiliary for stereocontrolled synthesis of salinosporamide analogs with modifications at positions C2 and C5. Bioorg Med Chem Lett 23:6905-10
Magauer, Thomas; Smaltz, Daniel J; Myers, Andrew G (2013) Component-based syntheses of trioxacarcin A, DC-45-A1 and structural analogues. Nat Chem 5:886-93
Hugelshofer, Cedric L; Mellem, Kevin T; Myers, Andrew G (2013) Synthesis of quaternary ?-methyl ?-amino acids by asymmetric alkylation of pseudoephenamine alaninamide pivaldimine. Org Lett 15:3134-7
Mellem, Kevin T; Myers, Andrew G (2013) A simple, scalable synthetic route to (+)- and (-)-pseudoephenamine. Org Lett 15:5594-7
Morales, Marvin R; Mellem, Kevin T; Myers, Andrew G (2012) Pseudoephenamine: a practical chiral auxiliary for asymmetric synthesis. Angew Chem Int Ed Engl 51:4568-71
Smaltz, Daniel J; Švenda, Jakub; Myers, Andrew G (2012) Diastereoselective additions of allylmetal reagents to free and protected syn-?,?-dihydroxyketones enable efficient synthetic routes to methyl trioxacarcinoside A. Org Lett 14:1812-5
Smaltz, Daniel J; Myers, Andrew G (2011) Scalable synthesis of enantiomerically pure syn-2,3-dihydroxybutyrate by Sharpless asymmetric dihydroxylation of p-phenylbenzyl crotonate. J Org Chem 76:8554-9
Magauer, Thomas; Myers, Andrew G (2011) Short and efficient synthetic route to methyl *-trioxacarcinoside B and anomerically activated derivatives. Org Lett 13:5584-7
Svenda, Jakub; Hill, Nicholas; Myers, Andrew G (2011) A multiply convergent platform for the synthesis of trioxacarcins. Proc Natl Acad Sci U S A 108:6709-14

Showing the most recent 10 out of 16 publications