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CC BY-ND-NC 4.0 · Synthesis 2019; 51(01): 225-232
DOI: 10.1055/s-0037-1611335
DOI: 10.1055/s-0037-1611335
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Chemoenzymatic Total Synthesis of (+)-Oxycodone from Phenethyl Acetate
The authors are grateful to the following agencies for financial support of this work: Natural Sciences and Engineering Research Council of Canada (NSERC) (Idea to Innovation and Discovery Grants), Canada Research Chair Program, Canada Foundation for Innovation (CFI), TDC Research, Inc., TDC Research Foundation, the Ontario Partnership for Innovation and Commercialization (OPIC), Noramco, Inc., and The Advanced Biomanufacturing Centre (Brock University).Further Information
Publication History
Received: 29 October 2018
Accepted: 31 October 2018
Publication Date:
20 November 2018 (online)
Abstract
The stereoselective total synthesis of unnatural (+)-oxycodone from phenethyl acetate is described. Absolute stereochemistry was established via microbial dihydroxylation of phenethyl acetate with the recombinant strain JM109 (pDTG601A) to the corresponding cis-cyclohexadienediol whose configuration provides for the absolute stereochemistry of the ring C of (+)-oxycodone. Intramolecular Heck cyclization was employed to establish the quaternary carbon at C-13, along with the dibenzodihydrofuran functionality. The C-14 hydroxyl was installed via SmI2-mediated radical cyclization. The synthesis of (+)-oxycodone was completed in a total of 13 steps and an overall yield of 1.5%. Experimental and spectral data are provided for all new compounds.
Key words
enzymatic dihydroxylation - total synthesis - oxycodone - Parker’s hydroamination - pinacol-type couplingSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611335. Included are spectral data for compounds 2, 3, 4, 6, 11, 12, 13, 14, ent-(1), 16.
- Supporting Information
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For use of these metabolites in synthesis, see: