Conformational Locking through Allylic Strain as a Device for Stereocontrol—Total Synthesis of Grandisine A

Authors

  • David J. Maloney Dr.,

    1. Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
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  • Samuel J. Danishefsky Prof.

    1. Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 106, New York, NY 10021, USA, Fax: (+1) 212-772-8691
    2. Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, USA
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  • This work was supported by the National Institutes of Health (grant CA103823). We are especially thankful to Julie Grinstead and Rebecca Lambert for assistance in the preparation of the manuscript and Dr. Brendan Crowley, Dr. Jeremy May, and Dr. Emile Velthuisen for helpful discussions during the course of this work.

Abstract

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Kontrollierte Fusion: Mit einer seco-Ring-D-Vorstufe für die Kontrolle der Stereochemie der entscheidenden Cycloaddition mit Acetaldehyd und der Richtung der Protonierung des resultierenden Silylenolethercycloaddukts gelang die Totalsynthese von Grandisin A, das eine vielversprechende Selektivität für die Bindung an den δ-Opioidrezeptor zeigt. Der Ring D wird zum Schluss aufgebaut (siehe Schema, LA=Lewis-Säure).

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