Oxindole-containing drug synthesis

The process chemists developed an ingenious route to couple 5-fluorooxindole with the pyrrole-containing right-hand piece. As shown below, pyrrole was added to a solution of the Vilsmeier reagent in acetonitrile at room temperature. Following the completion of the formylation reaction, the resulting intermediate was treated with 5-fluorooxindole and pulverized KOH, which led to precipitation of the desired product. Filtration of the reaction mixture afforded the sunitinib free base in 74% yield. 

In a later synthesis of the regioisomers of ropinirole, the isatin was formed from cyclization of a hydrazone under strong acidic conditions. After removal of the ketone functionality via hydrogenolysis and removal of the protective group, reductive amination afforded the regioisomer of ropinirole. 

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Batch reactors based on peroxidases are mainly applied for degradation purposes (see Chap. 8). LiP, manganese peroxidase (MnP), HRP, SBP, and CPO were used for the oxidation of phenolic compounds [3, 6, 7, 9, 20, 38, 74, 75, 95], decoloriza-tion of dye-containing effluents [5, 22], and pulp biobleaching [59]. In the field of synthesis, CPO is the most versatile and promising of the peroxidases (see Chap. 6). It was applied in discontinuous operation for epoxidations [78,79], enantioselective oxidations of alcohols to aldehydes [14,48], halogenations [77,80], hydroxylations, and oxidation of indole to oxindole, which is an important drug precursor [96]. 

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