Synthesis and antibacterial activity of nocathiacin I analogues.
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.
Naidu
B Narasimhulu
BN
The Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492, USA. b.narasimhulunaidu@bms.com
Sorenson
Margaret E
ME
Matiskella
John D
JD
Li
Wenying
W
Sausker
Justin B
JB
Zhang
Yunhui
Y
Connolly
Timothy P
TP
Lam
Kin S
KS
Bronson
Joanne J
JJ
Pucci
Michael J
MJ
Yang
Hyekyung
H
Ueda
Yasutsugu
Y
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects*; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013211:Staphylococcus aureus / Q000187:drug effects*; D013237:Stereoisomerism; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D000900:Anti-Bacterial Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C463319:nocathiacin I; D014867:Water