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12-Aza-Epothilones

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Signposts to Chiral Drugs

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Abstract

Biological target: 12-Aza-epothilones (azathilones) induce tubulin polymerization, thereby disturbing microtubule function and inhibiting mitosis and cell growth at nM concentrations. They show low susceptibility to P-glycoprotein-mediated efflux and are thus active on multidrug resistant cells.

Therapeutic profile: The compounds are potential anticancer agents.

Synthetic highlights: Natural macrocyclic compounds have been subjected to both extensive and peripheral structural modifications in the search for new lead compounds. An example of the former is the antibiotic azithromycin, whereas 12-aza-epothilones must be approached by total synthesis. This total synthesis of epothilones involves ring closure metathesis using heteroleptic complexes as catalysts and has proved to be an efficient approach to “non-natural, macrocyclic natural products”. In one of the critical steps of this pathway to azathilones, creative site-selective diimide reduction of an allylic C=C bond was applied.

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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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Šunjić, V., Parnham, M.J. (2011). 12-Aza-Epothilones. In: Signposts to Chiral Drugs. Springer, Basel. https://doi.org/10.1007/978-3-0348-0125-6_16

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