Biocatalytic synthesis towards both antipodes of 3-hydroxy-3-phenylpropanitrile a precursor to fluoxetine, atomoxetine and nisoxetine

Recent progress in biocatalysis for asymmetric oxidation and reduction

“…A library of 20 baker's yeast reductases over-expressed in E. coli was also screened against reduction of 3-oxo-3-phenylpropanenitrile for the synthesis of precursors for both antipodes of fluoxetine, atomoxetine, and nisoxetine, popular serotonin/norepinephrine reuptake inhibitors. 27 Four enzymes were found to reduce this substrate, and by changing the enzyme both enantiomers of 3-hydroxy-3-phenylpropanitrile could be prepared with a high ee as shown in Figure 18. In addition, the E. coli whole-cell system was optimized (a nitrogen-deficient media was used) to decrease the competing alkylating product (2Et-PPN) to 4-6% while the reduction with baker's yeast gave 90% yield of 2Et-PPN.…”

“…10 For the reduction of aromatic b-ketonitriles catalyzed by whole-cell biocatalysts over-expressing CMCR (yeast or E. coli whole cell), a-Ethylation concomitantly occurred. 27 Use of isolated CMCR with a catalytic amount of NADPH recycled by D-glucose and glucose dehydrogenase has completely eliminated this competing reaction, and (R)-b-hydroxy nitriles (97-99% ee) were successfully obtained. The products were further converted to (R)-bhydroxy carboxylic acids via a nitrilase-catalyzed hydrolysis.…”

A new convenient synthesis of some novel 2,6-disubstituted-pyridine derivatives

“…They provide miscellaneous building blocks in the synthesis of several types of heterocyclic ring systems based on a wide range of condensation and cyclization reactions. [1][2][3][4][5][6][7][8][9] On the other hand, a great deal of interest has been focused on the synthesis of the functionalized pyridine derivatives due to their biological activities. 10,11 For example, some 2-pyridine radicals are incorporated into the structures of cardiotonic agents such as milrinone 12 and HIV-1 specific transcriptase inhibitors.…”

Yeast‐Mediated Stereoselective Synthesis

“…Since the baker's yeast reduction of 3-oxo-3-phenylpropanenitrile has been difficult to achieve, a library of baker's yeast reductases was screened. As a result, this approach allowed the synthesis of both antipodes of antidepressants fluoxetine, atomoxetine, and nisoxetine [128]. Synthesis of (S)-1-(4-bromophenyl)-ethane-1,4-diol (11).…”