Synthesis and antimicrobial activity of binaphthyl-based, functionalized oxazole and thiazole peptidomimetics.
Thirty two new binaphthyl-based, functionalized oxazole and thiazole peptidomimetics and over thirty five novel leucine-containing intermediate oxazoles and thiazoles were prepared in this study. This includes the first examples of the direct C-5 arylation of an amino acid dipeptide-derived oxazole. Moderate to excellent antibacterial activity was observed for all new compounds across Gram positive isolates with MICs ranging from 1-16 μg mL(-1). Results for Gram negative E. coli and A. baumannii were more variable, but MICs as low as 4 μg mL(-1) were returned for two examples. Significantly, the in vitro results with a fluoromethyl-oxazole derivative collectively represent the best obtained to date for a member of our binaphthyl peptide antimicrobials.
School of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia. keller@uow.edu.au spyne@uow.edu.au.
Steven M
SM
Wales
Katherine A
KA
Hammer
Kittiya
K
Somphol
Isabell
I
Kemker
David C
DC
Schröder
Andrew J
AJ
Tague
Zinka
Z
Brkic
Amy M
AM
King
Dena
D
Lyras
Thomas V
TV
Riley
John B
JB
Bremner
Paul A
PA
Keller
Stephen G
SG
Pyne
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy; D006801:Humans; D008826:Microbial Sensitivity Tests; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D009281:Naphthalenes; D010080:Oxazoles; D057786:Peptidomimetics; D013844:Thiazoles; C412330:1,1'-binaphthyl