Abstract

The investigation, development, and implementation of two azadiene Diels-Alder reactions for the preparation of the two identical monomeric 1,2-dihydro-3H- pyrrolo[3.2-e]indole units (right-hand and central segments, PDE I/II) and the unusual cyclopropylpyrroloindole unit (left-hand segment) of CC-1065 (NSC 298233), the most potent antitumor-antibiotic isolated to date, are described.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041986-02
Application #
3182624
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1985-07-01
Project End
1987-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Purdue University
Department
Type
Schools of Arts and Sciences
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907

  Publications

Wolfe, Amanda L; Duncan, Katharine K; Lajiness, James P et al. (2013) A fundamental relationship between hydrophobic properties and biological activity for the duocarmycin class of DNA-alkylating antitumor drugs: hydrophobic-binding-driven bonding. J Med Chem 56:6845-57
Wolfe, Amanda L; Duncan, Katharine K; Parelkar, Nikhil K et al. (2013) Efficacious cyclic N-acyl O-amino phenol duocarmycin prodrugs. J Med Chem 56:4104-15
Wolfe, Amanda L; Duncan, Katharine K; Parelkar, Nikhil K et al. (2012) A novel, unusually efficacious duocarmycin carbamate prodrug that releases no residual byproduct. J Med Chem 55:5878-86
Lajiness, James P; Boger, Dale L (2011) Asymmetric synthesis of 1,2,9,9a-tetrahydrocyclopropa[c]benzo[e]indol-4-one (CBI). J Org Chem 76:583-7
Lajiness, James P; Boger, Dale L (2010) Synthesis and characterization of a cyclobutane duocarmycin derivative incorporating the 1,2,10,11-tetrahydro-9H-cyclobuta[c]benzo[e]indol-4-one (CbBI) alkylation subunit. J Am Chem Soc 132:13936-40
Boyle, Kristopher E; MacMillan, Karen S; Ellis, David A et al. (2010) Synthesis and evaluation of duocarmycin SA analogs incorporating the methyl 1,2,8,8a-tetrahydrocyclopropa[c]oxazolo[2,3-e]indol-4-one-6-carboxylate (COI) alkylation subunit. Bioorg Med Chem Lett 20:1854-7
Robertson, William M; Kastrinsky, David B; Hwang, Inkyu et al. (2010) Synthesis and evaluation of a series of C5'-substituted duocarmycin SA analogs. Bioorg Med Chem Lett 20:2722-5
Subramanian, Vidya; Williams, Robert M; Boger, Dale L et al. (2010) Methods to characterize the effect of DNA-modifying compounds on nucleosomal DNA. Methods Mol Biol 613:173-92
Lajiness, James P; Robertson, William M; Dunwiddie, Irene et al. (2010) Design, synthesis, and evaluation of duocarmycin O-amino phenol prodrugs subject to tunable reductive activation. J Med Chem 53:7731-8
MacMillan, Karen S; Lajiness, James P; Cara, Carlota Lopez et al. (2009) Synthesis and evaluation of a thio analogue of duocarmycin SA. Bioorg Med Chem Lett 19:6962-5

Showing the most recent 10 out of 62 publications