Abstract

As the computational methods used in pharmaceutical development improve, receptor binding analysis has led to many potential new drug candidates that are polycyclic. Such leads are often not pursued, however, because of the perception that even if the compound were active, an enantiomerically pure polycyclic candidate would be too expensive to manufacture. An investigation of a new method for the construction of carbocyclic rings, intramolecular alkylidene C-H insertion, is proposed. One could take nearly any complex cyclic molecule and do a retrosynthetic disconnection in such a way as to generate an alkylidene carbene precursor. Tetrodotoxin, N-deacetyllappaconitine and sordaricin have been selected as targets because of their structural interest and their pharmacological significance. In the course of these investigations, new molecular reactivity will be developed that will substantially shorten current routes to polycyclic natural products and drug candidates.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM060287-05A1
Application #
6777852
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Schwab, John M
Project Start
2000-04-01
Project End
2008-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
5
Fiscal Year
2004
Total Cost
$256,700
Indirect Cost

  Institution

Name
University of Delaware
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
059007500
City
Newark
State
DE
Country
United States
Zip Code
19716

  Publications

Taber, Douglass F; Berry, James F (2013) Construction of the tricyclic A-B-C core of the Veratrum alkaloids. J Org Chem 78:8437-41
Taber, Douglass F; DeMatteo, Peter W (2012) A piperidine chiron for the Veratrum alkaloids. J Org Chem 77:4235-41
Taber, Douglass F; Gerstenhaber, David A; Berry, James F (2012) Correction to enantioselective conjugate allylation of cyclic enones. J Org Chem 77:1215
Taber, Douglass F; Raciti, David M (2011) Synthesis of (-)-Astrogorgiadiol. Tetrahedron 67:10229-10233
Taber, Douglass F; Tirunahari, Pavan K (2011) Indole synthesis: a review and proposed classification. Tetrahedron 67:7195-7210
Taber, Douglass F; Bai, Sha; Tian, Weiwei (2011) Synthesis of the reported structure of trans-africanan-1?-ol. J Org Chem 76:9733-7
Taber, Douglass F; Nelson, Christopher G (2011) Aliphatic C-H to C-C conversion: synthesis of (-)-cameroonan-7?-ol. J Org Chem 76:1874-82
Taber, Douglass F; Guo, Pengfei; Pirnot, Michael T (2010) Conjugate addition of lithiated methyl pyridines to enones. J Org Chem 75:5737-9
Taber, Douglass F; Paquette, Craig M; Reddy, P Ganapati (2009) One Carbon Homologation of Halides to Benzyl Ethers. Tetrahedron Lett 50:2462-2463
Taber, Douglass F; Sheth, Ritesh B; Tian, Weiwei (2009) Synthesis of (+)-coronafacic acid. J Org Chem 74:2433-7

Showing the most recent 10 out of 39 publications