☆ 4.8 Article

Total Synthesis of (+)-Mutilin: A Transannular [2+2] Cycloaddition/Fragmentation Approach

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2022)

Journal

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Volume -, Issue -, Pages -

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AMER CHEMICAL SOC

DOI: 10.1021/jacs.2c06934

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Chemistry, Multidisciplinary

Funding

National Natural Science Foundation of China [31521004, 21672011, 21822101]
Lige-Zhaoning Youth Research Fund for Life Sciences, Ministry of Science and Technology [2017YFA0104000]
College of Chemistry and Molecular Engineering, Peking University
Peking Tsinghua Center for Life Sciences
Beijing National Laboratory for Molecular Sciences

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Abstract

A new and enantioselective total synthesis of the diterpenoid (+)-mutilin is described, which involves the Claisen rearrangement, transannular [2+2] photocycloaddition, ring-opening reaction, and subsequent late-stage alkylations and reduction to forge the characteristic skeleton.

A new and enantioselective total synthesis of the diterpenoid (+)-mutilin is described. Following a Claisen rearrangement approach to construct the 6,9-bicycle, a transannular [2+2] photocycloaddition and the ensuing ring-opening reaction were implemented to forge the characteristic 5-6-8 propellane-like skeleton. Subsequent late-stage alkylations and reduction completed the synthesis.

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