Synlett 2007(18): 2863-2867  
DOI: 10.1055/s-2007-990832
LETTER
© Georg Thieme Verlag Stuttgart · New York

Design for Morphine Alkaloids by Intramolecular Heck Strategy: Chemoenzymatic Synthesis of 10-Hydroxy-14-epi-dihydrocodeinone via C-D-B Ring Construction

Josef Zezulaa, Kenner C. Ricea, Tomas Hudlicky*b
a Drug Design and Synthesis Section, Chemical Biology Research Branch, Building 8, Room B1-23, , National Institute of Drug Abuse, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, 20892-0815, USA
b Department of Chemistry and Centre for Biotechnology, Brock University, 500 Glenridge Ave, St. Catharines, ON, L2S 3A1, Canada
Fax: +1(905)9844841; e-Mail: thudlicky@brocku.ca;
Further Information

Publication History

Received 17 July 2007
Publication Date:
15 October 2007 (online)

Abstract

Enzymatic dihydroxylation of β-bromoethylbenzene provided a homochiral diene diol that served as starting material for the synthesis of the complete morphinan skeleton via an intramolecular Heck cyclization.

19

For the description of model studies see ref. 1a.

25

It is likely that the hydrogenation of neopine-type compounds only proceeds to the natural configuration at C-14 in systems containing the full phenanthrene core, which is not the case with 14 or 15. The scarcity of material precluded us from performing the C-10-C-11 closure prior to hydrogenation.