Synthesis of four isotopically labeled forms of a proteasome inhibitor, bortezomib

Authors

  • Yuexian Li,

    Corresponding author
    1. Department of Drug Metabolism and Pharmacokinetics, Millennium Pharmaceuticals, Inc., 35 Landsdowne Street, Cambridge, MA 02139, USA
    • Department of Drug Metabolism and Pharmacokinetics, Millennium Pharmaceuticals, Inc., 35 Landsdowne Street, Cambridge, MA 02139, USA
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  • Mihaela Plesescu,

    1. Department of Drug Metabolism and Pharmacokinetics, Millennium Pharmaceuticals, Inc., 35 Landsdowne Street, Cambridge, MA 02139, USA
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  • Patrick Sheehan,

    1. Suffolk University, 8 Ashburton Place, Boston, MA 02108, USA
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  • J. Scott Daniels,

    1. Pharmacokinetics, Dynamics and Metabolism, Pfizer, Inc., St. Louis, MO 63017, USA
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  • Shimoga R. Prakash

    1. Department of Drug Metabolism and Pharmacokinetics, Millennium Pharmaceuticals, Inc., 35 Landsdowne Street, Cambridge, MA 02139, USA
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  • Proceedings of the Ninth International Symposium on the Synthesis and Applications of Isotopically Labelled Compounds, Edinburgh, 16–20 July 2006.

Abstract

[D2](1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]-amino]butyl] boronic acid ([D2]bortezomib), a proteasome inhibitor, was synthesized in 11 steps from isobutyryl chloride. Key steps in the synthesis included formation of the isobutyryl boronic acid via Grignard reaction and preparation of the chiral chloride using Matteson reaction. [13C9]bortezomib, [D5]bortezomib, and [D1]bortezomib were similarly synthesized from appropriate labeled precursors. Copyright © 2007 John Wiley & Sons, Ltd.

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