Total Synthesis of Leukotrienes from Butadiene

Authors

  • Ana Rodríguez,

    1. Department of Cell Biology, University of Medicine and Dentistry of New Jersey, SOM, 2, Medical Center Drive, Stratford, NJ 08084, USA, Fax: (internat.) +1-856/566-6195
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  • Miguel Nomen,

    1. Department of Cell Biology, University of Medicine and Dentistry of New Jersey, SOM, 2, Medical Center Drive, Stratford, NJ 08084, USA, Fax: (internat.) +1-856/566-6195
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  • Bernd W. Spur,

    1. Department of Cell Biology, University of Medicine and Dentistry of New Jersey, SOM, 2, Medical Center Drive, Stratford, NJ 08084, USA, Fax: (internat.) +1-856/566-6195
    2. Department of Respiratory Medicine and Allergy, King’s College London, Guy’s Hospital, London SE1 9RT, UK
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  • Jean-Jacques Godfroid,

    1. Laboratorie de Pharmacochimie Moléculaire, Université Paris 7, Paris 75251, France
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  • Tak H. Lee

    1. Department of Respiratory Medicine and Allergy, King’s College London, Guy’s Hospital, London SE1 9RT, UK
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  • Deceased September 26, 1997

Abstract

The total synthesis of leukotrienes has been achieved starting from butadiene by a palladium-catalyzed telomerization at room temperature. A Sharpless catalytic asymmetric epoxidation generated the asymmetric centers with >94% ee. Simple transformations of the key intermediate 15 produced the leukotrienes LTA4 methyl ester (4), LTC4 (1), LTD4 (2) and LTE4 (3), as well as (14S,15S)-LTA4 methyl ester (24) and the novel [2H2]-LTA4 methyl ester (28). The use of the opposite chiral director in the Sharpless catalytic asymmetric epoxidation gave the key intermediate 15a that has been used in the synthesis of the double epimers of the leukotrienes as well as LTB4.

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