Published January 31, 2018
| Accepted Version + Supplemental Material
Journal Article
Open
Total Synthesis of (+)-Pleuromutilin
Abstract
An 18-step synthesis of the antibiotic (+)-pleuromutilin is disclosed. The key steps of the synthesis include a highly stereoselective SmI2-mediated cyclization to establish the eight-membered ring and a stereospecific transannular [1,5]-hydrogen atom transfer to set the C10 stereocenter. This strategy was also used to prepare (+)-12-epi-pleuromutilin. The chemistry described here will enable efforts to prepare new mutilin antibiotics.
Additional Information
© 2018 American Chemical Society. Received: December 15, 2017; Published: January 11, 2018. We thank Dr. Michael Takase and Larry Henling for X-ray data collection, Ms. Julie Hofstra for X-ray data refinement, Dr. David VanderVelde for assistance with NMR structure determination, Dr. Scott Virgil for assistance with crystallization of 26, and the Caltech 3CS for access to analytical equipment. Fellowship support was provided by the NIH (E.P.F., Grant 1F32GM117764) and NSF (S.S.F., DGE-1144469). Financial support from the Heritage Medical Research Institute is gratefully acknowledged. The authors declare no competing financial interest.Attached Files
Accepted Version - nihms969583.pdf
Supplemental Material - ja7b13260_si_001.pdf
Supplemental Material - ja7b13260_si_002.zip
Files
ja7b13260_si_001.pdf
Additional details
- PMCID
- PMC5988231
- Eprint ID
- 84305
- Resolver ID
- CaltechAUTHORS:20180112-131323403
- F32GM117764
- NIH Postdoctoral Fellowship
- DGE-1144469
- NSF Graduate Research Fellowship
- Heritage Medical Research Institute
- Created
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2018-01-16Created from EPrint's datestamp field
- Updated
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2022-03-18Created from EPrint's last_modified field
- Caltech groups
- Heritage Medical Research Institute