Monoamine oxidases pyrrolidines

Improved efficiency in the synthesis of 24 was ultimately achieved via an enzymatic desymmetrization approach (Scheme 7). In the key step of this route, an asymmetric oxidation of achiral amine 41 promoted by monoamine oxidase (MAON) under an oxygen atmosphere afforded intermediate 42. In this streamlined process, sodium bisulfite was included in the enzymatic oxidation mixture to effect direct conversion to sulfonate 44. Treatment of 44 with sodium cyanide provided the trans-nitrile 43 as a single diastereomer in approximately 90% yield from pyrrolidine 41. As in the second-generation synthesis, the nitrile is hydrolyzed to the methyl ester under Pinner conditions (HCI, methanol). In the manufacturing process, the product was converted to its free base using NaOH, then crystallized as the HCI salt from i-propanol and methyl t-... 

This case discusses the preparation of 2,5-disubstituted pyrrolidines via TA/monoamine oxidase [85], Disubstituted pyrrolidines are important scaffolds in pharmaceutical compounds, such as (-F)-anatoxin-a [86] and are also common intermediates for the synthesis of many drug candidates [87,88]. In addition, disubstituted pyrrolidines are... 

Chemoenzymatic synthesis of 2,5-disubstituted pyrrolidines involving co-TA and monoamine oxidase [85]. 

E. O Reilly, C. Iglesias, D. Ghislieri, I. Hopwood, I.L. Galman, R.C. Lloyd, N.I. Turner, A regio-and stereoselective w-transaminase/monoamine oxidase cascade for the synthesis of chiral 2,5-disubstituted pyrrolidines, Angew. Chem. Int. Edit 53 (9) (2014) 2447-2450. 

Turner s group demonstrated that a variety of 3,4-substituted mcso-pyrrolidines can be enantioselectively oxidized by the monoamine oxidase (MAO) mutant. The -p3UToline products were converted to amino acids through the corresponding nitriles. In another application, the chiral A -pyrrolines were directly used to prepare prolyl peptides in an Ugj reaction. This reaction has been applied to an efficient synthesis of Telaprevir. The directed evolution of MAO from Aspergillus niger provided variant with a broadened substrate specificity and high enanhoselectivity for several a-methyl amines. In further enzyme evolution, an improved variant was identified for secondary amines [165,166]. 

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