Synthesis and antibacterial activity of nocathiacin I analogues

B Narasimhulu Naidu; Margaret E Sorenson; John D Matiskella; Wenying Li; Justin B Sausker; Yunhui Zhang; Timothy P Connolly; Kin S Lam; Joanne J Bronson; Michael J Pucci; Hyekyung Yang; Yasutsugu Ueda

doi:10.1016/j.bmcl.2006.03.079

Synthesis and antibacterial activity of nocathiacin I analogues

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3545-9. doi: 10.1016/j.bmcl.2006.03.079. Epub 2006 Apr 18.

Authors

B Narasimhulu Naidu¹, Margaret E Sorenson, John D Matiskella, Wenying Li, Justin B Sausker, Yunhui Zhang, Timothy P Connolly, Kin S Lam, Joanne J Bronson, Michael J Pucci, Hyekyung Yang, Yasutsugu Ueda

Affiliation

¹ The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. [email protected]

PMID: 16621551
DOI: 10.1016/j.bmcl.2006.03.079

Abstract

Stereoselective reduction of dehydroalanine double bond in nocathiacin I afforded the primary amide 2. Enzymatic hydrolysis of the amide 2 provided the carboxylic acid 3, which upon coupling with a variety of amines furnished amides 4-32. Some of these semi-synthetic derivatives have retained very good antibacterial activity and have improved aqueous solubility.

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Enterococcus faecalis / drug effects*
In Vitro Techniques
Intercellular Signaling Peptides and Proteins
Microbial Sensitivity Tests
Molecular Structure
Peptides / chemical synthesis*
Peptides / chemistry
Peptides / pharmacology*
Solubility
Staphylococcus aureus / drug effects*
Stereoisomerism
Streptococcus pneumoniae / drug effects*
Structure-Activity Relationship
Water / chemistry

Substances

Anti-Bacterial Agents
Intercellular Signaling Peptides and Proteins
Peptides
nocathiacin I
Water