Natural Products Chemistry, Merck Research Laboratories, 126 E Lincoln Avenue, Rahway, New Jersey 07065, USA.
J Nat Prod. 2009 May 22;72(5):841-7. doi: 10.1021/np800783b.
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.
噻唑肽是一类高度刚性的三大环化合物，由不同但数量众多的噻唑环组成。需要新的抗菌剂来治疗耐药菌引起的感染，这促使人们重新研究这一类化合物，导致以前分离出噻唑肽，即噻唑霉素（5）和噻唑霉素 A（6），是 nocathiacins（1-4）的同系物。持续的化学筛选导致分离出六个新的噻唑肽同系物（8-13），其中三个具有缺少吲哚残基的截断结构。其中，化合物 8 表现出与噻唑霉素相似的活性。两种化合物（9 和 10）表现出中等活性，而三个截断化合物（11-13）基本上没有活性。截断化合物的发现揭示了活性的最小结构要求，并暗示了更高级化合物的可能生物合成途径。本文描述了噻唑霉素的分离、结构阐明、抗菌活性和可能的生物发生。
