Elsevier

Tetrahedron Letters

Volume 47, Issue 41, 9 October 2006, Pages 7285-7287
Tetrahedron Letters

Expanding the medicinal chemistry toolbox: stereospecific generation of methyl group-containing propylene linkers

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Abstract

Use of alkyl substituted propylene linkers as a strategy for fine-tuning the biological activity of medicinal agents requires ready access to these substrates. Herein, a general strategy is described for stereospecifically generating 18 chiral mono- and di-methylpropylene linkers. All twelve vicinal 1,2-propylene targets were generated from methyl-3-hydroxybutanoate and all 1,3-disubstituted targets from pentane-2,4-diol.

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Acknowledgements

We are grateful to Jotham W. Coe and Professor Steven V. Ley for stimulating discussions.

References and notes (12)

  • B. Falkiewicz et al.

    Tetrahedron

    (2001)
    B.R. Castro

    Org. React.

    (1983)
    D.L. Hughes

    Org. Prep. Proced. Int.

    (1996)
    B.K. Shull et al.

    J. Org. Chem.

    (1997)
  • K. Hagiya et al.

    Tetrahedron: Asymmetry

    (2004)
    H. Brunner et al.

    Organometallics

    (1989)
  • T. Hintermann et al.

    Eur. J. Org. Chem.

    (1998)
    J.L. Matthews et al.

    Liebigs Annalen/Recueil

    (1997)
  • Ibuki, T.; Sugihara, T.; Kawakubo, H.; Sone, T. U.S. 4,533,731;...
  • C. Najera et al.

    Helv. Chim. Acta

    (1984)
There are more references available in the full text version of this article.

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