Published January 2009
| Supplemental Material + Accepted Version
Journal Article
Open
Chemo-enzymatic fluorination of unactivated organic compounds
Abstract
Fluorination has gained an increasingly important role in drug discovery and development. Here we describe a versatile strategy that combines cytochrome P450–catalyzed oxygenation with deoxofluorination to achieve mono- and polyfluorination of nonreactive sites in a variety of organic scaffolds. This procedure was applied for the rapid identification of fluorinated drug derivatives with enhanced membrane permeability.
Additional Information
© 2009 Nature Publishing Group. Received 11 August 2008; Accepted 27 October 2008; Published online 16 November 2008. We are grateful to M. Shahgholi for assistance with the LC-MS and HRMS analyses. This work was supported by US National Institutes of Health grant GM068664 and US Department of Agriculture grant 2006-35505-16660 to F.H.A. and by the Jacobs Institute (Caltech). A.R. acknowledges the Deutsche Forschungsgemeinschaft for financial support. Author contributions: R.F. and F.H.A. conceived the project; R.F. and A.R. performed the experiments; all authors discussed the results; R.F. wrote the paper with help and edits from F.H.A. and A.R. Declaration: R.F. and F.H.A. filed an international patent application (WO/2008/016709) entitled "Methods and systems for selective fluorination of organic molecules." Some of the P450 enzymes described in this work are available commercially from Codexis, Inc. F.H.A. is a minor shareholder of Codexis and serves on the Codexis Science Advisory Board.Attached Files
Accepted Version - nihms99645.pdf
Supplemental Material - RENncb09.cdx
Supplemental Material - RENncb09supp.pdf
Files
nihms99645.pdf
Additional details
- PMCID
- PMC2713661
- Eprint ID
- 13053
- Resolver ID
- CaltechAUTHORS:RENncb09
- GM068664
- NIH
- 2006-35505-16660
- Department of Agriculture (USDA)
- Jacobs Institute of Molecular Engineering for Medicine
- Deutsche Forschungsgemeinschaft (DFG)
- Created
-
2009-01-17Created from EPrint's datestamp field
- Updated
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2021-11-08Created from EPrint's last_modified field
- Caltech groups
- Jacobs Institute for Molecular Engineering for Medicine