Chemoenzymatic Formal Total Synthesis of ent‐Codeine and Other Morphinans via Nitrone Cycloadditions and/or Radical Cyclizations. Comparison of Strategies for Control of C‐9/C‐14 Stereogenic Centers. Issue 2 (7th February 2014)

• Record Type: Journal Article
• Authors: Endoma‐Arias, Mary Ann A.; Hudlicky, Jason Reed; Simionescu, Razvan; Hudlicky, Tomas
• Is Part Of: Advanced synthesis & catalysis. Volume 356:Issue 2/3(2014)
• Page Start: 333
• Page End: 339
• Publication Date: 2014-02-07
• Subjects: Catalysis -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Chemistry -- Periodicals; Chemistry, Technical -- Periodicals; Chemistry -- Periodicals; Catalysis -- Periodicals; Technology, Pharmaceutical -- Periodicals; 547.2
• DOI: 10.1002/adsc.201400016
• Languages: English
• ISSNs: 1615-4150

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Formal total syntheses of <italic>ent</italic>‐codeine and other morphinans were accomplished from 1‐phenyl‐2‐acetoxyethane, which was subjected to enzymatic dihydroxylation by toluene dioxygenase overexpressed in <italic>Eschericia coli</italic> JM109 (pDTG601A). The resulting <italic>cis</italic>‐dihydroarenediol was coupled with a phenol derived from bromoisovanillin and a subsequent Heck reaction was used to establish the C‐13 quaternary center. Two strategies were employed to set the C‐14 center: nitrone and nitrile oxide cycloadditions to the C‐8/C‐14 olefin and a radical cyclization of an aldehyde to C‐14. Both strategies yielded tetracyclic products that were converted to known intermediates for the synthesis of <italic>ent</italic>‐codeine, <italic>ent</italic>‐codeinone, and <italic>ent</italic>‐hydrocodone. Experimental and spectral data are provided for all new compounds.</p> <p> <boxed-text content-type="graphic" position="anchor" orientation="portrait"> <graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg4sr7r5mg" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /> </boxed-text> </p> </abstract>