Lincolnenins A-D：来自. 的同系物杀菌双蒽

Lincolnenins A-D: Isomeric Bactericidal Bianthracenes from .

机构信息

Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

出版信息

J Org Chem. 2021 Aug 20;86(16):11011-11018. doi: 10.1021/acs.joc.0c02492. Epub 2020 Dec 15.

DOI:10.1021/acs.joc.0c02492

PMID:33320674

Abstract

Cultivation profiling followed by chemical analysis of yielded four new isomeric bianthracenes, lincolnenins A-D (-), with relative stereostructures assigned on the basis of detailed spectroscopic analysis. Lincolnenins A () and B () exhibit restricted rotation about alternate bianthracene 9-9' and 9-8' bridges, respectively, and exist as single atropisomers, whereas C () and D () are thermally interconvertible atropisomers sharing a common 8-8' bianthracene bridge. Absolute configurations were assigned to - on the basis of diagnostic ROESY correlations and ECD calculations, whereas acid-mediated dehydration of led to formation and revision of the absolute configuration of the biosynthetically related known antibiotic, setomimycin (). Lincolnenin A () exhibited significant bactericidal activity against multiple susceptible and drug-resistant Gram-positive pathogens (MIC < 2.0 μM), including H37Ra (MIC = 0.9 μM).

摘要

通过培养分析和化学分析，从中得到了四个新的同型蒽并菲异构体，lincolnenins A-D (-)，基于详细的光谱分析确定了相对立体结构。Lincolnenins A () 和 B () 分别在交替的蒽并菲 9-9' 和 9-8' 桥处呈现受限旋转，并且作为单个非对映异构体存在，而 C () 和 D () 是热互变非对映异构体，共享一个共同的 8-8' 蒽并菲桥。根据诊断性 ROESY 相关和 ECD 计算，- 的绝对构型被分配，而酸介导的脱水导致生物合成相关的已知抗生素 setomimycin () 的绝对构型的形成和修订。Lincolnenin A () 对多种敏感和耐药革兰氏阳性病原体（MIC < 2.0 μM）表现出显著的杀菌活性，包括 H37Ra（MIC = 0.9 μM）。