Chemical conversion of nocathiacin I to nocathiacin II and a lactone analogue of glycothiohexide alpha.
Nocathiacin I (1) was converted to its deoxy indole analogue, nocathiacin II (2), another natural product, by a unique and facile chemical process. This process was applied to nocathiacin IV (4), generating the lactone analogue of glycothiohexide alpha (5), which was also prepared from nocathiacin II by a mild hydrolytic process. In contrast to glycothiohexide alpha (3), this lactone analogue (5) was found to exhibit in vivo antibacterial efficacy in an animal (mouse) infection model.
Connolly
Timothy P
TP
Pharmaceutical Research Institute, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, Connecticut 06492, USA.
Regueiro-Ren
Alicia
A
Leet
John E
JE
Springer
Dane M
DM
Goodrich
Jason
J
Huang
Xiaohua Stella
XS
Pucci
Michael J
MJ
Clark
Junius M
JM
Bronson
Joanne J
JJ
Ueda
Yasutsugu
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D004195:Disease Models, Animal; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D010456:Peptides, Cyclic; D013844:Thiazoles; C089609:glycothiohexide alpha; C463319:nocathiacin I; C500764:nocathiacin II; C473548:nocathiacin IV