Abstract

A renewal of our program directed toward the synthesis of potential antibiotics is sought. We hope to achieve the total synthesis and chemical characterization of pre-tyrosine, the immediate precursor of the aromatic amino acids, phenylalanine and tyrosine. This is a logical extension of our work in the prephenate field which would enable us to probe relationship of structural modifications and aromatase enzymic recognition in detail. A related program involves the synthesis of L-Dopa from glutamate in a fashion which preserves the optical integrity of the S-amino and chiral center. Analogs of prephenate and pretyrosine will be synthesized. Two new total synthesis efforts are envisioned. The first deals with the gram negative antibiotic, bicyclomycin. The other addresses the interesting quinonoid antibiotic naphthyridinomycin.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI016943-06
Application #
3126913
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1980-03-01
Project End
1989-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Type
Schools of Arts and Sciences
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code

  Publications

Carcache, David A; Cho, Young Shin; Hua, Zihao et al. (2006) Total synthesis of (+/-)-jiadifenin and studies directed to understanding its SAR: probing mechanistic and stereochemical issues in palladium-mediated allylation of enolate-like structures. J Am Chem Soc 128:1016-22
Hua, Zihao; Carcache, David A; Tian, Yuan et al. (2005) The synthesis and preliminary biological evaluation of a novel steroid with neurotrophic activity: NGA0187. J Org Chem 70:9849-56
Keding, Stacy J; Danishefsky, Samuel J (2004) Prospects for total synthesis: a vision for a totally synthetic vaccine targeting epithelial tumors. Proc Natl Acad Sci U S A 101:11937-42
Cho, Young Shin; Carcache, David A; Tian, Yuan et al. (2004) Total synthesis of (+/-)-jiadifenin, a non-peptidyl neurotrophic modulator. J Am Chem Soc 126:14358-9
Dudkin, Vadim Y; Miller, Justin S; Danishefsky, Samuel J (2004) Chemical synthesis of normal and transformed PSA glycopeptides. J Am Chem Soc 126:736-8
Krug, Lee M; Ragupathi, Govind; Hood, Chandra et al. (2004) Vaccination of patients with small-cell lung cancer with synthetic fucosyl GM-1 conjugated to keyhole limpet hemocyanin. Clin Cancer Res 10:6094-100
Warren, J David; Miller, Justin S; Keding, Stacy J et al. (2004) Toward fully synthetic glycoproteins by ultimately convergent routes: a solution to a long-standing problem. J Am Chem Soc 126:6576-8
Gaul, Christoph; Njardarson, Jon T; Danishefsky, Samuel J (2003) The total synthesis of (+)-migrastatin. J Am Chem Soc 125:6042-3
Miller, Justin S; Dudkin, Vadim Y; Lyon, Gholson J et al. (2003) Toward fully synthetic N-linked glycoproteins. Angew Chem Int Ed Engl 42:431-4
Coltart, Don M; Royyuru, Ajay K; Williams, Lawrence J et al. (2002) Principles of mucin architecture: structural studies on synthetic glycopeptides bearing clustered mono-, di-, tri-, and hexasaccharide glycodomains. J Am Chem Soc 124:9833-44

Showing the most recent 10 out of 26 publications