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Chemoenzymatic Total Synthesis of (+)-10-Keto-Oxycodone from Phenethyl Acetate.

ABSTRACT: The total synthesis of (+)-10-keto-oxycodone was attained from phenethyl acetate in a stereoselective manner. Absolute stereochemistry was established via enzymatic dihydroxylation of phenethyl acetate with the recombinant strain JM109 (pDTG601A) that furnished the corresponding cis-cyclohexadienediol whose configuration corresponds to the absolute stereochemistry of the ring C of (+)-10-keto-oxycodone. Intramolecular Heck reaction was utilized to establish the quaternary carbon at C-13, along with the dibenzodihydrofuran functionality. The C-14 hydroxyl and C-10 ketone were installed via SmI2-mediated radical cyclization, and oxidation of a benzylic alcohol (obtained from an intermediate nitrate azide), respectively. The synthesis of (+)-10-keto-oxycodone was completed in a total of 14 operations (21 steps) and an overall yield of ~2%. Experimental and spectral data are provided for key intermediates and new compounds.

SUBMITTER: Endoma-Arias MA

PROVIDER: S-EPMC6804203 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Chemoenzymatic Total Synthesis of (+)-10-Keto-Oxycodone from Phenethyl Acetate.

Endoma-Arias Mary Ann MA Dela Paz Helen H Hudlicky Tomas T

Molecules (Basel, Switzerland) 20190925 19

The total synthesis of (+)-10-keto-oxycodone was attained from phenethyl acetate in a stereoselective manner. Absolute stereochemistry was established via enzymatic dihydroxylation of phenethyl acetate with the recombinant strain JM109 (pDTG601A) that furnished the corresponding <i>cis</i>-cyclohexadienediol whose configuration corresponds to the absolute stereochemistry of the ring C of (+)-10-keto-oxycodone. Intramolecular Heck reaction was utilized to establish the quaternary carbon at C-13, ...[more]

PMID: 31557873

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