Efficient methodology to produce a duloxetine precursor using whole cells of Rhodotorula rubra

Different types of yeasts were employed as biocatalysts in the reduction of β-ketonitriles. The red microorganism, Rhodotorula rubra, was selected as the best performing catalyst in the reduction of different substituted ketonitriles giving total stereoselectivity in most cases (90–99% ee). In particular, its use as fresh and lyophilised cells was expanded to a semi-preparative scale for the production of the duloxetine precursor 1a. R. rubra was screened in the reduction of alkylation products in comparison with Pichia henricii for assignment of configuration of products 2a and 11a after derivatisation with S-MPA.

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(S)-3-Hydroxy-3-(thiophen-2-yl)propanenitrileC7H7NOSEe = 99% from HPLC[α]D20 = −42.1 (c 0.8, CHCl3)Source of chirality: Rhodotorula rubraAbsolute configuration: (S)