Total synthesis and preliminary SAR study of (±)-merochlorins A and B.
A modular synthesis of merochlorins A and B, two naturally occurring antibiotics, has been achieved concisely from readily available building blocks in 4-6 steps. The key steps include the bio-inspired tandem phenol oxidative dearomatization/[5 + 2] and [3 + 2] cycloadditions to construct the tricyclic cores of the targets, and the intermolecular Diels-Alder reaction followed by dehydrogenative aromatization to assemble the remaining aromatic units. The antibacterial activities of merochlorins A, B and some advanced synthetic intermediates were also evaluated, which provided valuable information on the structure-activity relationship (SAR) of this class of new antibiotics.
The Comprehensive AIDS Research Center, and Department of Pharmacology & Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, P.R. China. yefengtang@tsinghua.edu.cn.
Hongzhi
H
Yang
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China.
Xue
X
Liu
The Comprehensive AIDS Research Center, and Department of Pharmacology & Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, P.R. China. yefengtang@tsinghua.edu.cn.
Qingong
Q
Li
The Comprehensive AIDS Research Center, and Department of Pharmacology & Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, P.R. China. yefengtang@tsinghua.edu.cn.
Longbo
L
Li
Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China and Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Jing-Ren
JR
Zhang
The Comprehensive AIDS Research Center, and Department of Pharmacology & Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, P.R. China. yefengtang@tsinghua.edu.cn and Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Yefeng
Y
Tang
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D054830:Sesterterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D054830:Sesterterpenes; C573231:merochlorin A; C576411:merochlorin B