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Issue 28, 2015
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An investigation of nitrile transforming enzymes in the chemo-enzymatic synthesis of the taxol sidechain

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Abstract

Paclitaxel (taxol) is an antimicrotubule agent widely used in the treatment of cancer. Taxol is prepared in a semisynthetic route by coupling the N-benzoyl-(2R,3S)-3-phenylisoserine sidechain to the baccatin III core structure. Precursors of the taxol sidechain have previously been prepared in chemoenzymatic approaches using acylases, lipases, and reductases, mostly featuring the enantioselective, enzymatic step early in the reaction pathway. Here, nitrile hydrolysing enzymes, namely nitrile hydratases and nitrilases, are investigated for the enzymatic hydrolysis of two different sidechain precursors. Both sidechain precursors, an openchain α-hydroxy-β-amino nitrile and a cyanodihydrooxazole, are suitable for coupling to baccatin III directly after the enzymatic step. An extensive set of nitrilases and nitrile hydratases was screened towards their activity and selectivity in the hydrolysis of two taxol sidechain precursors and their epimers. A number of nitrilases and nitrile hydratases converted both sidechain precursors and their epimers.

Graphical abstract: An investigation of nitrile transforming enzymes in the chemo-enzymatic synthesis of the taxol sidechain

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Publication details

The article was received on 11 Jun 2015, accepted on 17 Jun 2015 and first published on 24 Jun 2015


Article type: Paper
DOI: 10.1039/C5OB01191D
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Citation: Org. Biomol. Chem., 2015,13, 7803-7812
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    An investigation of nitrile transforming enzymes in the chemo-enzymatic synthesis of the taxol sidechain

    B. Wilding, A. B. Veselá, J. J. B. Perry, G. W. Black, M. Zhang, L. Martínková and N. Klempier, Org. Biomol. Chem., 2015, 13, 7803
    DOI: 10.1039/C5OB01191D

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