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A desymmetrization-based approach to morphinans: application in the total synthesis of oxycodone
Kun Ho Kenny Park1, David Y-K Chen
1Department of Chemistry, Seoul National University, Gwanak-1 Gwanak-ro, Gwanak-gu, Seoul 08826, South Korea. davidchen@snu.ac.kr.
Abstract:
Here we report a total synthesis of the pharmacologically significant morphinan alkaloid, oxycodone. The centerpiece of the developed strategy features the first application of the Rovis desymmetrization of peroxyquinol in target-oriented total synthesis to access an optically active phenanthrene framework shared by the morphinans. A Stork-Ueno radical cyclization under photoredox conditions installed the all-carbon quaternary stereocenter, and a late-stage reductive detosylation with concomitant piperidine formation secured the core structure of the target molecule.
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