Abstract

Studies designed to elucidate the mechanism-of-action of the antitumor antibiotic neocarzinostatin are proposed. A convergent and expeditious plan for the laboratory synthesis of the neocarzinostatin chromophore is presented which features methodology of general validity for structural congeners. The proposed studies will conclusively establish the stereochemical designation of the antibiotic and promise to be of value for the preparation of related new DNA-cleaving molecules and drug substances.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29CA047148-04
Application #
3458836
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
4
Fiscal Year
1991
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

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
Simmons, Rebecca L; Yu, Robert T; Myers, Andrew G (2011) Storable arylpalladium(II) reagents for alkene labeling in aqueous media. J Am Chem Soc 133:15870-3
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 14 publications