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

Vimal Varghese; Tomas Hudlicky

doi:10.1055/s-0032-1318114

Synlett, Table of Contents

Synlett 2013; 24(3): 369-374
DOI: 10.1055/s-0032-1318114

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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

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Abstract

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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.

Key words

enzymatic dihydroxylation of arenes - whole-cell fermentation - Kazmaier–Claisen rearrangement - hydrocodone - dihydrocodeine - morphine alkaloids

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References

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