Unknown

Dataset Information

0

A modular and enantioselective synthesis of the pleuromutilin antibiotics.


ABSTRACT: The tricyclic diterpene fungal metabolite (+)-pleuromutilin has served as a starting point for antibiotic development. Semisynthetic modification of its glycolic acid subunit at C14 provided the first analogs fit for human use, and derivatization at C12 led to 12-epi-pleuromutilins with extended-spectrum antibacterial activity, including activity against Gram-negative pathogens. Given the inherent limitations of semisynthesis, however, accessing derivatives of (+)-pleuromutilin with full control over their structure presents an opportunity to develop derivatives with improved antibacterial activities. Here we disclose a modular synthesis of pleuromutilins by the convergent union of an enimide with a bifunctional iodoether. We illustrate our approach through synthesis of (+)-12-epi-mutilin, (+)-11,12-di-epi-mutilin, (+)-12-epi-pleuromutilin, (+)-11,12-di-epi-pleuromutilin, and (+)-pleuromutilin itself in 17 to 20 steps.

SUBMITTER: Murphy SK 

PROVIDER: S-EPMC7001679 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications

A modular and enantioselective synthesis of the pleuromutilin antibiotics.

Murphy Stephen K SK   Zeng Mingshuo M   Herzon Seth B SB  

Science (New York, N.Y.) 20170601 6341


The tricyclic diterpene fungal metabolite (+)-pleuromutilin has served as a starting point for antibiotic development. Semisynthetic modification of its glycolic acid subunit at C14 provided the first analogs fit for human use, and derivatization at C12 led to 12-<i>epi</i>-pleuromutilins with extended-spectrum antibacterial activity, including activity against Gram-negative pathogens. Given the inherent limitations of semisynthesis, however, accessing derivatives of (+)-pleuromutilin with full  ...[more]

Similar Datasets

| S-EPMC9633427 | biostudies-literature
| S-EPMC3160647 | biostudies-literature
| S-EPMC5727219 | biostudies-literature
| S-EPMC7001007 | biostudies-literature
| S-EPMC7146891 | biostudies-literature
| S-EPMC5988231 | biostudies-literature
| S-EPMC7145359 | biostudies-literature
| S-EPMC8193914 | biostudies-literature
| S-EPMC8576787 | biostudies-literature
| S-EPMC7024634 | biostudies-literature