286846-65-9

Upstream product

• 3042-21-5 2-methyl-5-phenyl-1H-pyrrole 
• 583-05-1 1-phenylpentane-1,4-dione 
• 98-86-2 acetophenone 

Downstream Products

• 1357391-22-0 (2S,5R)-2-methyl-5-phenylpyrrolidine 
• 1357391-22-0 (2S,5S)-2-methyl-5-phenylpyrrolidine 

Relevant academic research and scientific papers

Development of a: Corynebacterium glutamicum bio-factory for self-sufficient transaminase reactions

The development of biocatalytic routes for the synthesis of chiral amines starting from achiral building blocks is highly desirable. Here, we report a self-sufficient whole-cell system for the conversion of a model ketone to the corresponding cyclic imine, in good isolated yield (42%) and excellent enantioselectivity (>99% ee). The Corynebacterium glutamicum host produces the transaminase biocatalyst, cofactor and 'smart' amine donor (cadaverine or putrescine) in vivo, and highlights the potential for producing high-value chemicals from readily available building blocks. The report represents the first example of the application of a metabolically engineered organism for the production of smart diamine donors and their application in a transaminase biotransformation.

Synthesis of 2,5-Disubstituted Pyrrolidine Alkaloids via A One-Pot Cascade Using Transaminase and Reductive Aminase Biocatalysts

A multi-enzymatic cascade process involving transaminases (TAs) and reductive aminases (RedAms) to produce enantiomerically pure 2,5-disubstituted pyrrolidine alkaloids from their respective 1,4-diketones is reported. Several TAs were screened and the best results for diketone monoamination were obtained with an R-selective TA from Mycobacterium chlorophenicum and with an S-selective TA from Bacillus megaterium. Pyrroline reduction was best performed by a reductive aminase from Ajellomyces dermatitidis (AdRedAm). Finally, a biocatalytic one-pot cascade was implemented using the aforementioned enzymes and a variety of 2-methyl-5-alkylpyrrolidines were produced with high (>99 %) conversion, diastereomeric and enantiomeric excess values.

One-Pot Cascade Synthesis of Mono- and Disubstituted Piperidines and Pyrrolidines using Carboxylic Acid Reductase (CAR), ω-Transaminase (ω-TA), and Imine Reductase (IRED) Biocatalysts

Access to enantiomerically pure chiral mono- and disubstituted piperidines and pyrrolidines has been achieved using a biocatalytic cascade involving carboxylic acid reductase (CAR), ω-transaminase (ω-TA), and imine reductase (IRED) enzymes. Starting from keto acids or keto aldehydes, substituted piperidine or pyrrolidine frameworks can be generated in high conversion, ee, and de in one pot, with each biocatalyst exhibiting chemo-, regio-, and/or stereoselectivity during catalysis. The study also includes a systematic investigation of the effect of the position of a methyl group ring substituent on the IRED-catalyzed reduction of a chiral imine. Analysis of the selectivity observed in these reactions revealed an interesting balance between substrate versus enzyme control; the configurations of the products obtained were rationalized on the basis of minimizing 1,3- or 1,2-steric interactions with incoming NADPH.

A regio- and stereoselective ω-transaminase/monoamine oxidase cascade for the synthesis of chiral 2,5-disubstituted pyrrolidines

Biocatalytic approaches to the synthesis of optically pure chiral amines, starting from simple achiral building blocks, are highly desirable because such motifs are present in a wide variety of important natural products and pharmaceutical compounds. Herein, a novel one-pot ω-transaminase (TA)/monoamine oxidase (MAO-N) cascade process for the synthesis of chiral 2,5-disubstituted pyrrolidines is reported. The reactions proceeded with excellent enantio- and diastereoselectivity (>94 % ee; >98 % de) and can be performed on a preparative scale. This methodology exploits the complementary regio- and stereoselectivity displayed by both enzymes, which ensures that the stereogenic center established by the transaminase is not affected by the monoamine oxidase, and highlights the potential of this multienzyme cascade for the efficient synthesis of chiral building blocks. Mirror mirror on the wall: A ω-transaminase (ω-TA)/monoamine oxidase (MAO-N) cascade process for the asymmetric synthesis of chiral 2,5-disubstituted pyrrolidines is reported. The methodology exploits the complementary regio- and stereoselectivity displayed by both enzymes, which ensures that the stereogenic center established by the TA reaction is not affected by the MAO-N catalyzed step. Copyright

Highly enantioselective partial hydrogenation of simple pyrroles: A facile access to chiral 1-pyrrolines

A highly enantioselective Pd-catalyzed partial hydrogenation of simple 2,5-disubstituted pyrroles with a Bronsted acid as an activator has been successfully developed, providing chiral 2,5-disubstituted 1-pyrrolines with up to 92% ee.