Challenges in the synthesis of a unique mono-carboxylic acid antibiotic, (+)-zincophorin.
(+)-Zincophorin, also referred to as M144255 or griseocholin, is a polyoxygenated ionophoric antibiotic that was isolated from Streptomyces griseus in 1984. It possesses strong in vivo activity against Gram-positive bacteria and Clostridium coelchii. Its methyl ester was reported in a patent as having strong inhibitory properties against influenza WSN/virus with reduced toxicity for the host cell. Its ability to strongly bind with Zn2+, which is also present in its X-ray structure, is the basis for its name. Over the last two decades, (+)-zincophorin has attracted an impressive array of synthetic efforts including Danishefsky's first total synthesis, along with two recent elegant total syntheses reported by Cossy and Miyashita as well as our own formal total synthesis. This review provides a comparison of the different synthetic efforts on this novel mono-carboxylic acid antibiotic and documents its interesting isolation, structure determination, and biological activities.
Song
Zhenlei
Z
Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy, West China Hospital, Sichuan University, Chengdu 610041, PR China. zhenleisong@scu.edu.cn
Lohse
Andrew G
AG
Hsung
Richard P
RP
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011422:Propionates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013305:Streptomyces griseus / Q000737:chemistry
D000900:Anti-Bacterial Agents; D011422:Propionates; C043279:zincophorin