Structures, Reactivities, and Antibiotic Properties of the Marinopyrroles A−F

Cultivation of actinomycete strain CNQ-418, retrieved from a deep ocean sediment sample off the coast of La Jolla, CA, has provided marinopyrroles A−F. Sharing just 98% 16S rRNA gene sequence identity with S. sannurensis, the strain likely represents a new Streptomyces species. The metabolites contain an unusual 1,3′-bipyrrole core decorated with several chlorine and bromine substituents and possess marked antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The congested N,C-biaryl bond establishes an axis of chirality that, for marinopyrroles A−E, is configurationally stable at room temperature. Moreover, the natural products are fashioned strictly in the M-configuration. The Paal−Knorr condensation was adapted for the synthesis of the 1,3′-bipyrrole core. Halogenation of this material with N-bromosuccinimide cleanly furnished the 4,4′,5,5′-tetrahalogenated core that characterizes this class of marine-derived metabolites.

从加利福尼亚州拉霍亚外海深海沉积物样本中分离得到的放线菌菌株CNQ-418，其培养实验成功获得了marinopyrroles A−F。该菌株与S. sannurensis的16S rRNA基因序列同源性仅为98%，推测其为链霉菌属（Streptomyces）的一个新物种。其代谢产物含有一种罕见的1,3′-二吡咯核心结构，该核心带有多个氯、溴取代基，且对耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus, MRSA）具有显著的抗菌活性。该拥挤的N,C-联芳键形成了一个手性轴，对于marinopyrroles A−E而言，其在室温下构型稳定。此外，这类天然产物严格以M构型存在。研究人员将Paal−Knorr缩合反应（Paal−Knorr condensation）用于1,3′-二吡咯核心结构的合成。以N-溴代琥珀酰亚胺（N-bromosuccinimide，NBS）对该核心结构进行卤代反应，可高效得到该类海洋来源代谢产物所特有的4,4′,5,5′-四卤代核心结构。