Abstract

As a foundation upon which new medicinal agents can be constructed, it is important to uncover simple, yet powerful methods for the synthesis of core organic functionalities, as well as methods that allow the core structures to be easily substituted with a wide variety of substituents. It is in support of health sciences in general that the chemistry proposed within finds its significance. Because of the unique ability of transition metal species to effect the formation of carbon-carbon and carbon-heteroatom bonds under very mild conditions, emphasis in this proposal is placed on the use of organotransition metal chemistry to facilitate a variety of transformations. An underlying theme of the proposed chemistry is the development of flexible new synthetic methods that will facilitate the structure-activity-relationship studies that lead to the discovery of new medicinal agents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM066153-22
Application #
7005401
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
1998-03-20
Project End
2009-08-31
Budget Start
2006-01-01
Budget End
2009-08-31
Support Year
22
Fiscal Year
2006
Total Cost
$255,987
Indirect Cost

  Institution

Name
Emory University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Varela-Alvarez, Adrian; Liebeskind, Lanny S; Musaev, Djamaladdin G (2012) Mechanistic Insights into the Aerobic Cu(I)-Catalyzed Cross-Coupling of S-Acyl Thiosalicylamide Thiol Esters and Boronic Acids. Organometallics 31:7958-7968
Li, Hao; He, Anyu; Falck, John R et al. (2011) Stereocontrolled synthesis of ?-amino-?'-alkoxy ketones by a copper-catalyzed cross-coupling of peptidic thiol esters and ?-alkoxyalkylstannanes. Org Lett 13:3682-5
Zhang, Zhihui; Lindale, Matthew G; Liebeskind, Lanny S (2011) Mobilizing Cu(I) for carbon-carbon bond forming catalysis in the presence of thiolate. Chemical mimicking of metallothioneins. J Am Chem Soc 133:6403-10
Wu, Wenting; Zhang, Zhihui; Liebeskind, Lanny S (2011) In situ carboxyl activation using a silatropic switch: a new approach to amide and peptide constructions. J Am Chem Soc 133:14256-9
Musaev, Djamaladdin G; Liebeskind, Lanny S (2009) On the Mechanism of Pd(0)-Catalyzed, Cu(I) Carboxylate-Mediated Thioorganic-Boronic Acid Desulfitative Coupling. A Non-innocent Role for Carboxylate Ligand. Organometallics 28:4639-4642
Zitomer, Nicholas C; Mitchell, Trevor; Voss, Kenneth A et al. (2009) Ceramide synthase inhibition by fumonisin B1 causes accumulation of 1-deoxysphinganine: a novel category of bioactive 1-deoxysphingoid bases and 1-deoxydihydroceramides biosynthesized by mammalian cell lines and animals. J Biol Chem 284:4786-95
Liebeskind, Lanny S; Yang, Hao; Li, Hao (2009) A copper-catalyzed, pH-neutral construction of high-enantiopurity peptidyl ketones from peptidic s-acylthiosalicylamides in air at room temperature. Angew Chem Int Ed Engl 48:1417-21
Li, Hao; Yang, Hao; Liebeskind, Lanny S (2008) Synthesis of high enantiopurity N-protected alpha-amino ketones by thiol ester-organostannane cross-coupling using pH-neutral conditions. Org Lett 10:4375-8
Liu, Songbai; Liebeskind, Lanny S (2008) A simple, modular synthesis of substituted pyridines. J Am Chem Soc 130:6918-9
Zhang, Zhihui; Yu, Ying; Liebeskind, Lanny S (2008) N-amidation by copper-mediated cross-coupling of organostannanes or boronic acids with o-acetyl hydroxamic acids. Org Lett 10:3005-8

Showing the most recent 10 out of 20 publications