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 coupling
