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Synthesis 2004(17): 2905-2909  
DOI: 10.1055/s-2004-831245
PAPER
© Georg Thieme Verlag Stuttgart · New York

Convergent Diastereoselective Synthesis of Isopilocarpine by One-Pot Michael-Addition-Alkylation Reaction

Manfred Braun*a, Corinna Bühnea, Dimitrula Cougalia, Klaus Schapera, Walter Frankb
a Institut für Organische Chemie und Makromolekulare Chemie, Universität Düsseldorf, 40225 Düsseldorf, Germany
Fax: +49(211)8115079; e-Mail: braunm@uni-duesseldorf.de;
b Institut für Anorganische Chemie und Strukturchemie, Universität Düsseldorf, 40225 Düsseldorf, Germany
Further Information

Publication History

Received 19 July 2004
Publication Date:
29 September 2004 (online)

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Abstract

The metalated dithiane 7b available from imidazole aldehyde 6 is reacted with furanone 4 and ethyl iodide to give the lactone 8, which forms diastereoselectively. Its configuration is determined to be trans by means of a crystal structure analysis. The desulfurization of 8 leads to the alkaloid isopilocarpine 2 in three steps and 25% overall yield. The relative energies of the diastereomeric alkaloids 1 and 2 have been calculated.

Key words

alkaloids - diastereoselectivity - drugs - lactones - metalations

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Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC 249730. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44(1223)336033 or e-mail: deposit@ccdc.cam.ac.uk).