Monoamine oxidases -enantiomer

Monoamine oxidases are enzymes that catalyze the racemization of ot-amino acids 186). Both l- and D-selective monoamine oxidases are known (i.e., they catalyze the racemization of either S)- or (R)-enantiomers of amino acids). This property has been exploited to obtain enantiomerically pure (R) and S) amino acids by using an appropriate achiral reducing agent such as NaBH4, NaB(CN)H3, or H3N BH3 in combination with an l- or D-selective monoamine oxidase 187). 

The group of Turner has reported the deracemization of amines [79]. The wild type of Type II monoamine oxidase from Aspergillus niger possesses very low but measurable activity toward the oxidation of L-a-methylbenzylamine. The oxidation of the D enantiomer is even slower. In vitro evolution led to the identification of a mutant with enhanced enantioselectivity, showing high E values (>100) for a variety of primary and secondary amines. An example is shown in Scheme 5.39. 

Tranylcypromine is a chiral monoamine oxidase inhibitor used in the treatment of depression. The drug is similar to mefloquine in that it is contains a diastereomeric structure but is only administered as the 50 50 combination of the (- -)-lS,2R and (—)-lR,2S species. The enantiomers possess differences in their pharmacological properties in that (-I-) tranylcypromine is much more effective than its antipode in MAO inhibition, but the (—) enantiomer causes greater diminution of catecholamine reuptake and release than (-I-) enantiomer [147]. With respect to its pharmacokinetics (Table 1), the (-I-) enantiomer seemed to be cleared via the oral route 4 to 8 times more rapidly than antipode based on significantly... 

The method has been applied to study the enantiomer recognition of the protein monoamine oxidase (MAO), which has been used for affinity liquid chromatography. A mutant preparation method has been described using D-amino acid oxidase (DAO). The optimized structure of the docked complex between a protein and a substrate is obtained by performing molecular mechanics calculations, and the data indicates the degree of complex tightness. 

The reactions were highly regioselective and only minor side products were formed (4-10% yields) under the established conditions. In addition, this reaction could also be carried out on a 500 mg scale under mild conditions. Recently, Kroutil and co-workers developed a novel chemo-en matic derace-mization reaction, which involves two enantioselective oxidation steps and one non-stereoselective reduction step. This concept combines stereoinversion of one substrate enantiomer with a kinetic resolution to transform a racemic substrate to an optically pure product. By using this method, dera-cemization of benzylisoquinolines rac-39 to berbines (S)-41 via the cascade transformation using monoamine oxidase (MAO), BBE, and morpholine-bo-rane concurrently gave optically pure product [S]-41 (>97% ee, HPLC) in up to 88% isolated yield (Scheme 2.14c). 

Turner et al. first reported engineered S-stereoselective flavin-dependent monoamine oxidase variants bom Aspergillus niger for the deracemization of racemic amines producing the S-enantiomers of primary, secondary, and tertiary amines (Figure 19.8) [35]. On the other hand, Leisch et al. showed that wild-type cyclohexy-lamine oxidase from Brevibacterium oxydans IH-35A, which had been isolated and characterized by Hasegawa et al., oxidized the S-enantiomer of amines and successfully synthesized (f )-amine through a deracemization reaction [37]. 

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