Abstract

The total synthesis of deoxybouvardin and bouvardin (NSC 259968), ususual bicyclic hexapeptides with confirmed antitumor propeties, are detailed. Antitumor and antimicrobial structure-activity relationships of deoxybouvardin and bouvardin, including the evaluation of partial structures, are to be pursued. The approach to the preparation of deoxybouvardin and bouvardin relies on the development and implementation of approaches to the preparation of the unusual diaryl ether linked cyclic 14-membered dipeptide ( a meta- and paracyclophane dipeptide) evidently required for antitumor activity, and its incorporation into the bicyclic hexapeptide structure constituting the structural framework of the naturally occurring materials.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041101-02
Application #
3181410
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
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

Wu, Zhi-Chen; Isley, Nicholas A; Boger, Dale L (2018) N-Terminus Alkylation of Vancomycin: Ligand Binding Affinity, Antimicrobial Activity, and Site-Specific Nature of Quaternary Trimethylammonium Salt Modification. ACS Infect Dis 4:1468-1474
Okano, Akinori; Isley, Nicholas A; Boger, Dale L (2017) Peripheral modifications of [?[CH2NH]Tpg4]vancomycin with added synergistic mechanisms of action provide durable and potent antibiotics. Proc Natl Acad Sci U S A 114:E5052-E5061
Okano, Akinori; Isley, Nicholas A; Boger, Dale L (2017) Total Syntheses of Vancomycin-Related Glycopeptide Antibiotics and Key Analogues. Chem Rev 117:11952-11993
Boger, Dale L (2017) The Difference a Single Atom Can Make: Synthesis and Design at the Chemistry-Biology Interface. J Org Chem 82:11961-11980
Okano, Akinori; Nakayama, Atsushi; Wu, Kejia et al. (2015) Total syntheses and initial evaluation of [?[C(?S)NH]Tpg?]vancomycin, [?[C(?NH)NH]Tpg?]vancomycin, [?[CH?NH]Tpg?]vancomycin, and their (4-chlorobiphenyl)methyl derivatives: synergistic binding pocket and peripheral modifications for the glycopeptide antib J Am Chem Soc 137:3693-704
Lee, Kiyoun; Poudel, Yam B; Glinkerman, Christopher M et al. (2015) Total synthesis of dihydrolysergic acid and dihydrolysergol: development of a divergent synthetic strategy applicable to rapid assembly of D-ring analogs. Tetrahedron 71:5897-5905
Hou, L; Jiang, J; Liu, B et al. (2014) Association between smoking and deaths due to colorectal malignant carcinoma: a national population-based case-control study in China. Br J Cancer 110:1351-8
Okano, Akinori; Nakayama, Atsushi; Schammel, Alex W et al. (2014) Total synthesis of [?[C(?NH)NH]Tpg(4)]vancomycin and its (4-chlorobiphenyl)methyl derivative: impact of peripheral modifications on vancomycin analogues redesigned for dual D-Ala-D-Ala and D-Ala-D-Lac binding. J Am Chem Soc 136:13522-5
Nakayama, Atsushi; Okano, Akinori; Feng, Yiqing et al. (2014) Enzymatic glycosylation of vancomycin aglycon: completion of a total synthesis of vancomycin and N- and C-terminus substituent effects of the aglycon substrate. Org Lett 16:3572-5
Pinchman, Joseph R; Boger, Dale L (2013) Probing the role of the vancomycin e-ring aryl chloride: selective divergent synthesis and evaluation of alternatively substituted E-ring analogues. J Med Chem 56:4116-24

Showing the most recent 10 out of 59 publications