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Signposts to Chiral Drugs pp 179–195Cite as

Paclitaxel

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Abstract

Biological target: Paclitaxel is a natural polysubstituted macrocyclic compound isolated from the bark of the Pacific yew tree (Taxus brevifolia). It binds to β-tubulin, causing polymerisation of the tubulin, thereby disrupting normal microtubule dynamics required for cell division.

Therapeutic profile: Paclitaxel (Taxol ®) is an anticancer agent with a broad spectrum of activity against tumours that are often refractive to other drugs.

Synthetic highlights: The partial synthesis of paclitaxel was necessary to enhance the availability of the drug substance and avoid unsustainable use of yew trees. Many different synthetic routes have been reported and three inventive pathways for the enantioselective or site-selective approaches to various segments of the paclitaxel molecule are described. These are all promoted by organometal catalytic complexes. Reactions presented include use of the intramolecular Heck reaction in the synthetic pathway to baccatine III; the Sharpless reaction and the introduction of a trifunctional catalyst for biomimetic synthesis of chiral diols; synthesis of the paclitaxel side-chain; and use of a Zr-complex catalyst in the reductive N-deacylation of taxanes to primary amine, the key precursor of paclitaxel.

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Authors and Affiliations

  1. Faculty of Natural Sciences and Mathematics Department of Organic Chemistry, University of Zagreb, Horvatovac 102A, HR-10000, Zagreb, Croatia

    Prof. Dr. Vitomir Šunjić

  2. Research and Clinical Immunology Departments, University Hospital for Infectious Diseases “Dr. Fran Mihaljevic”, Mirogojska cesta 8, HR-10000, Zagreb, Croatia

    Prof. Dr. Michael J. Parnham

Authors
  1. Prof. Dr. Vitomir Šunjić
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  2. Prof. Dr. Michael J. Parnham
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Correspondence to Vitomir Šunjić .

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© 2011 Springer Basel AG

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Šunjić, V., Parnham, M.J. (2011). Paclitaxel. In: Signposts to Chiral Drugs. Springer, Basel. https://doi.org/10.1007/978-3-0348-0125-6_14

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