Synthesis of Enantiomerically Pure Ring-Substituted <scp>l</scp>-Pyridylalanines by Biocatalytic Hydroamination

Ahmed, Syed Thouheed; Parmeggiani, Fabio; Weise, Nicholas J.; Flitsch, Sabine L.; Turner, Nicholas J.

doi:10.1021/acs.orglett.6b02559

Cited by 23 publications

(22 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, in our recent effort to prepare a broad panel of arylalanines from arylaldehydes, [24] exploiting the AvPAL-mediated hydroamination as a key step, the same behaviour was observed. For several of the pyridylacrylic acids tested, albeit under different conditions than those reported in this study, an additional amino acid product was apparent from the NMR analysis after prolonged incubation with the biocatalyst, reaching in some cases a consistent proportion of the crude mixture (see ESM).…”

Section: Resultssupporting

confidence: 52%

Discovery and Investigation of Mutase-like Activity in a Phenylalanine Ammonia Lyase from Anabaena variabilis

et al. 2018

Self Cite

View full text Add to dashboard Cite

The effect of extended reaction times on the regio-and enantioselectivity of the phenylalanine ammonia lyase (PAL)-catalysed amination of a subset of cinnamate derivatives was investigated. This was done using a PAL from the cyanobacterium Anabaena variabilis and incubation in a concentrated ammonia buffer. Whilst early time point analyses revealed excellent selectivities to give mostly the well-documented (S)-α-amino acid products, subsequent accumulation of other regio-/stereo-isomers was seen. For many para-substituted substrates, the β-regioisomer, a previously-unreported product with this enzyme class, was found to become more abundant than the α-, after sufficient incubation, with slight preference for the (R)-enantiomer. Although attempts to tune the selectivity of the PAL toward any of the three side products were largely unsuccessful, the results provide insight into the evolutionary history of this class of enzymes and reinforce the prominence of the toolbox of specific and selective cinnamate-aminating enzymes.

show abstract

Section: Resultssupporting

confidence: 52%

Discovery and Investigation of Mutase-like Activity in a Phenylalanine Ammonia Lyase from Anabaena variabilis

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cycles are versatile and important structural moieties present in organic molecules, which act as good modifiers of properties and biological activities . Functionalization of amino acids with cycles is a subject of great interest, leading to a diversity of useful noncanonical amino acids with broad applications . Here we report the asymmetric synthesis of various N ‐cycloalkyl‐substituted L‐aspartic acids using MAL‐Q73A and EDDS lyase as biocatalysts.…”

Section: Methodsmentioning

confidence: 99%

“…[23][24][25][26] Functionalization of amino acids with cycles is a subject of great interest, leading to a diversity of useful noncanonical amino acids with broad applications. [27][28][29] Here we report the asymmetric synthesis of various Ncycloalkyl-substituted L-aspartic acids using MAL-Q73A and EDDS lyase as biocatalysts. This biocatalytic methodology provides an alternative synthetic choice to prepare difficult N-cycloalkyl-substituted amino acids.…”

mentioning

confidence: 99%

Biocatalytic Enantioselective Hydroaminations for Production of N‐Cycloalkyl‐Substituted L‐Aspartic Acids Using Two C−N Lyases

Zhang

Tepper

et al. 2019

Adv Synth Catal

View full text Add to dashboard Cite

N-cycloalkyl-substituted amino acids have wide-ranging applications in pharma-and nutraceutical fields. Here we report the asymmetric synthesis of various N-cycloalkyl-substituted laspartic acids using ethylenediamine-N,N'-disuccinic acid lyase (EDDS lyase) and a previously engineered variant of methylaspartate ammonia lyase (MAL-Q73A) as biocatalysts. Particularly, EDDS lyase shows broad non-natural substrate promiscuity and excellent enantioselectivity, allowing the selective addition of homo-and heterocycloalkyl amines (comprising four-, five-and sixmembered rings) to fumarate, giving the corresponding N-cycloalkyl-substituted l-aspartic acids with > 99% e.e. This biocatalytic methodology offers an alternative synthetic choice to prepare difficult N-cycloalkyl-substituted amino acids. Given its very broad amine scope, EDDS lyase is an exceptionally powerful synthetic tool that nicely complements the rapidly expanding toolbox of biocatalysts for asymmetric synthesis of noncanonical amino acids.

show abstract

“…In general, excellent conversions and enantioselectivities up to >99% were achieved, although the products were recovered in 32-60% isolated yield after column chromatography (Ahmed 2016). The substrates that displayed a worse enantioselectivity were submitted to an additional step of deracemisation cascade employing an aminoacid acid oxidase (DAAO) coupled with ammonia-borane, thus obtaining the desired products with >99% ee in every case.…”

Section: Scheme 28 Enzymatic Hydroxylation Of Testosterone With a Pementioning

confidence: 99%

Stereoselective biocatalysis: A mature technology for the asymmetric synthesis of pharmaceutical building blocks

Albarrán-Velo

González‐Martínez

Gotor‐Fernández

2017

Biocatalysis and Biotransformation

View full text Add to dashboard Cite

Biocatalysis is gaining increasing attention in the academic and industrial sector due to the possibility of developing highly stereoselective transformations in a sustainable manner. The creation of stereogenic centers in organic synthesis is not trivial and multiple approaches have been disclosed based on 2 organometallic and organocatalytic methods with the use of day by day more complex catalysts to induce asymmetry in selected transformations. The intrinsic chirality of enzymes makes them powerful tools for the development of stereoselective transformations, catalysing a wide range of chemical reactions due to the high abundance and diversity of enzymes in nature. In addition, the enormous advances in rational design and molecular biology methods have opened up the possibility to create more robust and versatile biocatalysts, which have improved the initial activities displayed by wild-type enzymes. Therefore, their applicability has been widely increased in terms of reaction conditions, substrate specificity, activity and selectivity among others. All these properties have attracted the industrial sector, which has taken advantage of the enzyme selectivities in multiple scenarios. Herein, the focus has been put in recent developments of stereoselective transformations for the synthesis of valuable building blocks towards the production of pharmaceuticals and biologically active natural products.

show abstract

Synthesis of Enantiomerically Pure Ring-Substituted l-Pyridylalanines by Biocatalytic Hydroamination

Cited by 23 publications

References 28 publications

Discovery and Investigation of Mutase-like Activity in a Phenylalanine Ammonia Lyase from Anabaena variabilis

Discovery and Investigation of Mutase-like Activity in a Phenylalanine Ammonia Lyase from Anabaena variabilis

Biocatalytic Enantioselective Hydroaminations for Production of N‐Cycloalkyl‐Substituted L‐Aspartic Acids Using Two C−N Lyases

Stereoselective biocatalysis: A mature technology for the asymmetric synthesis of pharmaceutical building blocks

Contact Info

Product

Resources

About