Abstract

The development and exploitation of alkynyliodonium salts for stereoselective organic synthesis will be pursued. These reagents display unique reactivity patterns which permit polycyclic chemical structures to be assembled readily from simple acyclic precursors. In particular, the use of nitrogen-containing addends with these salts will lead to efficient construction of the molecular framework of several pharmaceutically interesting alkaloids including members of the Cephalotaxus group, as well as agelastatin A, magellaninone, and palau'amine. Several of these target structures (e.g., deoxyharringtonine, agelastatin A) display very promising antileukemic and antineoplastic activity, while palau'amine elicits an immunomodulatory response. Timely acquisition of these bioactive targets through alkynyliodonium salt methodology will contribute to an understanding of their mechanism of action and will provide lead structures for further optimization/evaluation of biological activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037681-11
Application #
6018678
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1987-01-01
Project End
2000-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
11
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Pennsylvania State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802

  Publications

Feldman, Ken S; Selfridge, Brandon R (2010) EXPLORATION OF BRAVERMAN REACTION CHEMISTRY. SYNTHESIS OF TRICYCLIC DIHYDROTHIOPHENE DIOXIDE DERIVATIVES FROM BISPROPARGYL SULFONES. Heterocycles 81:117-143
Feldman, Ken S; Iyer, Malliga R; Silva Lopez, Carlos et al. (2008) Allenyl azide cycloaddition chemistry: exploration of the scope and mechanism of cyclopentennelated dihydropyrrole synthesis through azatrimethylenemethane intermediates. J Org Chem 73:5090-9
Feldman, Ken S; Coca, Adiel (2008) Synthesis of the pentacyclic core of lihouidine. Tetrahedron Lett 49:2136-2138
Feldman, Ken S; Hester 2nd, D Keith; Golbeck, John H (2007) A relationship between amide hydrogen bond strength and quinone reduction potential: implications for photosystem I and bacterial reaction center quinone function. Bioorg Med Chem Lett 17:4891-4
Feldman, Ken S; Eastman, Kyle J (2006) Studies on the mechanism of action of prekinamycin, a member of the diazoparaquinone family of natural products: evidence for both sp2 radical and orthoquinonemethide intermediates. J Am Chem Soc 128:12562-73
Feldman, Ken S; Eastman, Kyle J (2005) A proposal for the mechanism-of-action of diazoparaquinone natural products. J Am Chem Soc 127:15344-5
Feldman, Ken S; Perkins, Angela L; Masters, Katherine M (2004) Alkynyliodonium salts in organic synthesis. Application to the preparation of the tricyclic core of (+/-)-halichlorine. J Org Chem 69:7928-32
Feldman, Ken S; Saunders, Joe C (2002) Alkynyliodonium salts in organic synthesis. Application to the total synthesis of (-)-agelastatin A and (-)-agelastatin B. J Am Chem Soc 124:9060-1
Feldman, Ken S; Cutarelli, Timothy D; Di Florio, Romina (2002) Total synthesis of the tropoloisoquinoline alkaloid pareitropone via alkynyliodonium salt chemistry and related studies. J Org Chem 67:8528-37
Feldman, Ken S; Cutarelli, Timothy D (2002) Alkynyliodonium salts in organic synthesis. Application to the total synthesis of the tropoloisoquinoline alkaloid pareitropone. J Am Chem Soc 124:11600-1

Showing the most recent 10 out of 13 publications