title: Thiazomycins, thiazolyl peptide antibiotics from Amycolatopsis fastidiosa.
abstract: Thiazolyl peptides are a class of highly rigid trimacrocyclic compounds consisting of varying but large numbers of thiazole rings. The need for new antibacterial agents to treat infections caused by resistant bacteria prompted a reinvestigation of this class, leading to the previous isolation of thiazolyl peptides, namely, thiazomycin (5) and thiazomycin A (6), congeners of nocathiacins (1-4). Continued chemical screening led to the isolation of six new thiazolyl peptide congeners (8-13), of which three had truncated structures lacking an indole residue. From these, compound 8 showed activity similar to thiazomycin. Two compounds (9 and 10) showed intermediate activities, and the three truncated compounds (11-13) were essentially inactive. The discovery of the truncated compounds revealed the minimal structural requirements for activity and suggested probable biosynthetic pathways for more advanced compounds. The isolation, structure elucidation, antibacterial activity, and proposed biogenesis of thiazomycins are herein described.
authors.affiliation: Natural Products Chemistry, Merck Research Laboratories, 126 E Lincoln Avenue, Rahway, New Jersey 07065, USA.
authors.forename: Chaowei
authors.initials: C
authors.lastname: Zhang
authors.forename: Kithsiri
authors.initials: K
authors.lastname: Herath
authors.forename: Hiranthi
authors.initials: H
authors.lastname: Jayasuriya
authors.forename: John G
authors.initials: JG
authors.lastname: Ondeyka
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Zink
authors.forename: James
authors.initials: J
authors.lastname: Occi
authors.forename: Gwyneth
authors.initials: G
authors.lastname: Birdsall
authors.forename: Jayashree
authors.initials: J
authors.lastname: Venugopal
authors.forename: Misti
authors.initials: M
authors.lastname: Ushio
authors.forename: Bruce
authors.initials: B
authors.lastname: Burgess
authors.forename: Prakash
authors.initials: P
authors.lastname: Masurekar
authors.forename: John F
authors.initials: JF
authors.lastname: Barrett
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh