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. 2022 Jun 15;144(23):10174-10179.
doi: 10.1021/jacs.2c04708. Epub 2022 Jun 2.

Synthesis of Pleuromutilin

Nicholas J Foy  1 , Sergey V Pronin  1
Affiliations

Synthesis of Pleuromutilin

Nicholas J Foy et al. J Am Chem Soc. .

Abstract

Synthesis of a potent inhibitor of bacterial protein synthesis, pleuromutilin, is described. Assembly of the critical cyclooctane fragment relies on an oxidative ring-expansion, and complete stereochemical relay in the synthetic sequence is enabled by the judicious choice of tactics. The requisite connectivity pattern of the perhydroindanone motif is rapidly established in a sequence of cycloaddition and radical cyclization events. Application of this strategy allows for preparation of the target natural product in 16 steps from commercially available material.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Representative mutilin antibiotics and our approach to the shared tricyclic motif.
Figure 2.
Figure 2.
Computed lowest energy conformations of enols 21 and 22. Computations were performed at the ωB97X-D/6-31G(d) level of theory.
Scheme 1.
Scheme 1.
Synthesis of Tricyclic Diketone 9
Scheme 2.
Scheme 2.
Synthesis of Pleuromutilin (1)
See this image and copyright information in PMC

References

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