Abstract

This grant will continue a research program to investigate the fundamental chemistry of recently discovered, bioloically active natural products. Our plans include two major target areas for study. Firstly, our continuing efforts for synthesis of the pseudomonic acids A, B, and C are nearing completion. These studies have led to the development of efficient strategies for prepartion of L-carbohydrates and stereochemically complex oxacyclic systems. The major emphasis of this proposal describes strategies for highly convergent, enantiospecific investigations of the chemistry of the lankacidins. These unique macrocyclic metabolites display considerable antitumor activity against L1210 leukemia, B16 melanoma, and solid lymphosarcoma, in vivo, and are only weakly toxic in mice. They also show strong atimicrobial activities, principally against Gram-positive bacteria, including some strains of clinically resistant isolates.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM041560-09
Application #
3299770
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1982-04-01
Project End
1992-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Indiana University Bloomington
Department
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401

  Publications

Williams, David R; Claeboe, Christopher D; Liang, Bo et al. (2012) A bidirectional S(E)' strategy for 1,5-syn and 1,5-anti stereocontrol toward the synthesis of complex polyols. Org Lett 14:3866-9
Williams, David R; Klein, J Cullen; Chow, Nicholas S C (2011) Studies of intramolecular Diels-Alder reactions of nitroalkenes for the stereocontrolled synthesis of trans-decalin ring systems. Tetrahedron Lett 52:2120-2123
Williams, David R; Walsh, Martin J; Claeboe, Christopher D et al. (2009) Studies for the synthesis of marine natural products. Pure Appl Chem 81:181
Williams, David R; Nag, Partha P; Zorn, Nicolas (2008) Strategies for the synthesis of the novel antitumor agent peloruside A. Curr Opin Drug Discov Devel 11:251-71
Williams, David R; Reeves, Jonathan T; Nag, Partha P et al. (2006) Studies of the generation and pericyclic behavior of cyclic pentadienyl carbanions. Alkylation reactions as an efficient route to functionalized cis-bicyclo[3.3.0]octenes. J Am Chem Soc 128:12339-48
Williams, David R; Morales-Ramos, Angel I; Williams, Catherine M (2006) Reactivity studies of 3,3-bis(trimethylsilyl)-2-methyl-1-propene in Lewis acid-catalyzed allylation reactions. Org Lett 8:4393-6
Williams, David R; Berliner, Martin A; Stroup, Bryan W et al. (2005) Samarium Barbier reactions of alpha-iodomethyloxazoles and thiazoles with aliphatic aldehydes. Org Lett 7:4099-102
Williams, David R; Kammler, David C; Donnell, Andrew F et al. (2005) Total synthesis of (+)-apiosporamide: assignment of relative and absolute configuration. Angew Chem Int Ed Engl 44:6715-8
Williams, David R; Reeves, Jonathan T (2004) Carbolithiation for the generation of cyclooctadienyl anions and tandem electrocyclization/alkylation to functionalized cis-bicyclo[3.3.0]octenes. J Am Chem Soc 126:3434-5
Williams, David R; Kiryanov, Andre A; Emde, Ulrich et al. (2004) Studies of stereocontrolled allylation reactions for the total synthesis of phorboxazole A. Proc Natl Acad Sci U S A 101:12058-63

Showing the most recent 10 out of 20 publications