Synlett 2013; 24(3): 369-374
DOI: 10.1055/s-0032-1318114
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© Georg Thieme Verlag Stuttgart · New York

Total Synthesis of Dihydrocodeine and Hydrocodone via a Double Claisen Rearrangement and C-10/C-11 Closure Strategy

Vimal Varghese
Chemistry Department and Centre for Biotechnology, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario L2S 3A1, Canada   Fax: +1(905)9844841   Email: thudlicky@brocku.ca
,
Tomas Hudlicky*
Chemistry Department and Centre for Biotechnology, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario L2S 3A1, Canada   Fax: +1(905)9844841   Email: thudlicky@brocku.ca
› Author Affiliations
Further Information

Publication History

Received: 06 December 2012

Accepted after revision: 04 January 2013

Publication Date:
21 January 2013 (online)


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Abstract

Dihydrocodeine and hydrocodone were synthesized from bromobenzene in 16 and 17 transformations, respectively. The key steps involved the toluene dioxygenase-mediated dihydroxy­lation of bromobenzene by whole-cell fermentation with E. coli JM109(pDTG601A), Kazmaier–Claisen rearrangement of glycinate ester, Claisen rearrangement to set the C-13 quaternary center, and C-10–C-11 closure. Experimental procedures are provided for the key steps.