Abstract

Many therapeutically important natural products and pharmaceutical agents can be prepared from functionalized cyclopentane and dioxolane derivatives. The continued development of methodology for the efficient and stereoselective synthesis of these ring systems is proposed. This methodology is based on the free radical mediated addition of functionalized olefins or related species across the carbon-carbon bond of suitably activated vinylcyclopropanes to afford directly the cyclopentane units. Emphasis is placed on enhancing current levels of dia- stereoselectivity and enantioselectivity upon bond formation. Further, the development of novel free radical-based annelation/isomerization reactions for the construction of highly functionalized cyclopentanol species is planned. Finally, diastereoselective remote (Gamma) functionalization of secondary alcohols will be explored. Syntheses of the antitumor antibiotic brefeldin A and The antileukemic agent rocaglamide, which each utilize intramolecular variants of the cyclo- pentannelation process, will be investigated. Successful completion of these syntheses will afford the targets (or analogs) in the most efficient manner to date.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037681-07
Application #
2178888
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1987-01-01
Project End
1996-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
7
Fiscal Year
1995
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