An investigation of nitrile transforming enzymes in the chemo-enzymatic synthesis of the taxol sidechainElectronic supplementary information (ESI) available: NMR spectra of all compounds, experimental procedures for acid and amide reference materials, representative HPLC chromatograms of biotransformation reactions from non-chiral and chiral HPLC measurements, biotransformations with cosolvents, information on commercial enzyme preparations. See DOI: 10.1039/c5ob01191d

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-(2 R ,3 S )-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. Nitrile transforming enzymes, namely nitrilases and nitrile hydratases, are investigated for the enzymatic hydrolysis of two taxol sidechain precursors, an openchain α-hydroxy-β-amino nitrile and a cyanodihydrooxazole.