CC BY-ND-NC 4.0 · Synthesis 2019; 51(01): 225-232
DOI: 10.1055/s-0037-1611335
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Chemoenzymatic Total Synthesis of (+)-Oxycodone from Phenethyl Acetate

Mary Ann A. Endoma-Arias
,
Mariia Makarova
,
Helen E. Dela Paz
,
Chemistry Department and Centre for Biotechnology, Brock University, 1812 Sir Isaac Brock Way St. Catharines, Ontario, L2S 3A1, Canada   Email: thudlicky@brocku.ca
› Author Affiliations
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 (eFirst)

  

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.

Supporting Information

 
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