Abstract

The total synthesis of a number of marine natural products in the polyketide and diterpene families will be undertaken. The targeted compounds exhibit high levels of growth inhibition against various human tumor cell lines but they are generally not readily available from natural sources in quantities amenable to their evaluation as drug candidates. In addition, we will synthesize analogues of some of the more active compounds that will be tested for differential cytotoxicity against tumor vs. normal human cell lines by Professor F. Valeriote at the Josephine Ford Cancer Center in Detroit. The main chemical issues to be addressed include the control of stereochemistry by means of chiral organometal chemistry and the design of new and efficient routes to structurally novel natural products.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA090383-02
Application #
6514951
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Lees, Robert G
Project Start
2001-03-01
Project End
2005-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
2
Fiscal Year
2002
Total Cost
$230,508
Indirect Cost

  Institution

Name
University of Virginia
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Marshall, James A; Schaaf, Gregory; Nolting, Andrew (2005) Synthesis of the C6-C21 segment of amphidinolide E. Org Lett 7:5331-3
Marshall, James A; Mulhearn, James J (2005) Synthesis of a C20-C26 segment of superstolide a by addition of a chiral allenylzinc reagent to (R)-N-boc alaninal. Org Lett 7:1593-6
Marshall, James A; Sabatini, Jesse J (2005) Synthesis of cis- and trans-2,5-disubstituted tetrahydrofurans by a tandem dihydroxylation-SN2 cyclization sequence. Org Lett 7:4819-22
Marshall, James A; Eidam, Patrick (2004) Diastereoselective additions of chiral vinylzinc reagents to alpha-chiral aldehydes. Org Lett 6:445-8
Marshall, James A; Bourbeau, Matthew P (2003) Synthesis of enantioenriched propargylic alcohols related to polyketide natural products. A comparison of methodologies. Org Lett 5:3197-9
Marshall, James A; Chobanian, Harry R (2003) Synthesis of 2,5-disubstituted tetrahydrofurans by stereospecific elimination-cyclization of 1-iodomethyl-1,5-bis-epoxides. Org Lett 5:1931-3
Marshall, James A; Ellis, Keith C (2003) Total synthesis of (-)- and (+)-membrenone C. Org Lett 5:1729-32
Marshall, James A; Schaaf, Gregory M (2003) Total synthesis and structure confirmation of leptofuranin D. J Org Chem 68:7428-32
Marshall, James A; Bourbeau, Matthew P (2002) Second-generation synthesis of the polypropionate subunit of callystatin A based on regioselective internal alkyne hydrostannation. Org Lett 4:3931-4
Marshall, James A; Adams, Nicholas D (2002) Total synthesis of bafilomycin V(1): a methanolysis product of the macrolide bafilomycin C(2). J Org Chem 67:733-40

Showing the most recent 10 out of 14 publications