Abstract

(Principal Investigator's) The broad, long-term objectives of thi proposal are: (1) to develop new synthetic methods of use in the design and development of anticancer, antibiotic, and possibly antiviral drugs, and (2) to develop novel methods for the delivery and in vivo activation of anticancer drugs. The facile and controlled introduction of varied substituents about an aromati or heteroaromatic core during structure-activity relationship studies is a recurring problem encountered in the development of many new medicinal agents that are based on small organic molecules. This remains an important factor in drug development even with the advent of combinatorial chemistry, which identifies but does not optimize drug leads. To accomplish this important goal new methods are proposed that are based upon """"""""biominetic"""""""" cross-coupling using coenzyme A and coenzyme M mimics. Cyclobutenedione-based synthetic methods have matured to the point that they now are ready for incorporation into challenging, non-methodological problems. Using cyclobutenedione methodology as a seminal component of each system, metallaquinones and porphyrin quinones are being developed as novel anticancer agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040157-16
Application #
2856257
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Lees, Robert
Project Start
1998-03-20
Project End
2001-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
16
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Emory University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Yang, Hao; Li, Hao; Wittenberg, Rudiger et al. (2007) Ambient temperature synthesis of high enantiopurity N-protected peptidyl ketones by peptidyl thiol ester-boronic acid cross-coupling. J Am Chem Soc 129:1132-40
Aguilar-Aguilar, Angelica; Liebeskind, Lanny S; Pena-Cabrera, Eduardo (2007) Pd-catalyzed, Cu(I)-mediated cross-couplings of bisarylthiocyclobutenediones with boronic acids and organostannanes. J Org Chem 72:8539-42
Liu, Songbai; Yu, Ying; Liebeskind, Lanny S (2007) N-substituted imines by the copper-catalyzed N-imination of boronic acids and organostannanes with O-acyl ketoximes. Org Lett 9:1947-50
Egi, Masahiro; Liebeskind, Lanny S (2003) Heteroaromatic thioether-organostannane cross-coupling. Org Lett 5:801-2
Liebeskind, Lanny S; Srogl, Jiri (2002) Heteroaromatic thioether-boronic acid cross-coupling under neutral reaction conditions. Org Lett 4:979-81
Savarin, Cecile; Srogl, Jiri; Liebeskind, Lanny S (2002) A mild, nonbasic synthesis of thioethers. The copper-catalyzed coupling of boronic acids with N-thio(alkyl, aryl, heteroaryl)imides. Org Lett 4:4309-12
Deng, X; Liebeskind, L S (2001) A contribution to the design of molecular switches: novel acid-mediated ring-closing--photochemical ring-opening of 2,3-bis(heteroaryl)quinones (heteroaryl = thienyl, furanyl, pyrrolyl). J Am Chem Soc 123:7703-4
Savarin, C; Srogl, J; Liebeskind, L S (2001) Substituted alkyne synthesis under nonbasic conditions: copper carboxylate-mediated, palladium-catalyzed thioalkyne-boronic acid cross-coupling. Org Lett 3:91-3
Savarin, C; Liebeskind, L S (2001) Nonbasic, room temperature, palladium-catalyzed coupling of aryl and alkenyl iodides with boronic acids mediated by copper(I) thiophene-2-carboxylate (CuTC). Org Lett 3:2149-52
Savarin, C; Srogl, J; Liebeskind, L S (2000) Thiol ester-boronic acid cross-coupling. Catalysis using alkylative activation of the palladium thiolate intermediate. Org Lett 2:3229-31

Showing the most recent 10 out of 12 publications