scholarly journals N-Phenylputrescine (NPP): A Natural Product Inspired Amine Donor for Biocatalysis

2021 ◽  
Author(s):  
Catherine McKenna ◽  
Mária Štiblariková ◽  
Irene De Silvestro ◽  
Dominic Campopiano ◽  
Andrew Lawrence
Keyword(s):  
Chemical Synthesis ◽  
Natural Product ◽  
Driving Forces ◽  
Enzyme Engineering ◽  
Chiral Amines ◽  
Reaction Conditions ◽  
Fine Chemical ◽  
Donor Acceptor ◽  
Prochiral Ketones

The synthesis of chiral amines in enantioenriched form is a keystone reaction in applied chemical synthesis. There is a strong push to develop greener and more sustainable alternatives to the metal-catalysed methods currently used in the pharmaceutical, agrochemical and fine chemical industries. A biocatalytic approach using transaminase (TA or ATA) enzymes to convert prochiral ketones to chiral amines with unparalleled levels of enantioselectivity is highly appealing. However, the use of TA enzymes in synthesis is severely hampered by the unfavourable thermodynamics associated with the amine donor/acceptor equilibrium. Several ‘smart’ amine donors have been developed that leverage chemical and physical driving forces to overcome this challenging equilibrium. Alongside this strategy, enzyme engineering is typically required to develop TAs compatible with these non-physiological amine donors and the unnatural reaction conditions they require. We herein disclose N-phenylputrescine (NPP) as a readily accessible amine donor, inspired by the biosynthesis of the dipyrroloquinoline alkaloids. NPP is compatible with a broad range of synthetically useful TA biocatalysts and performs across an unparalleled variety of reaction conditions (pH and temperature). Synthetic applicability has been demonstrated through the synthesis of the anti-diabetic drug sitagliptin, delivering the product in excellent enantiopurity using just two equivalents of NPP<br>

scholarly journals N-Phenylputrescine (NPP): A Natural Product Inspired Amine Donor for Biocatalysis

2021 ◽  
Author(s):  
Catherine McKenna ◽  
Mária Štiblariková ◽  
Irene De Silvestro ◽  
Dominic Campopiano ◽  
Andrew Lawrence
Keyword(s):  
Chemical Synthesis ◽  
Natural Product ◽  
Driving Forces ◽  
Enzyme Engineering ◽  
Chiral Amines ◽  
Reaction Conditions ◽  
Fine Chemical ◽  
Donor Acceptor ◽  
Prochiral Ketones

The synthesis of chiral amines in enantioenriched form is a keystone reaction in applied chemical synthesis. There is a strong push to develop greener and more sustainable alternatives to the metal-catalysed methods currently used in the pharmaceutical, agrochemical and fine chemical industries. A biocatalytic approach using transaminase (TA or ATA) enzymes to convert prochiral ketones to chiral amines with unparalleled levels of enantioselectivity is highly appealing. However, the use of TA enzymes in synthesis is severely hampered by the unfavourable thermodynamics associated with the amine donor/acceptor equilibrium. Several ‘smart’ amine donors have been developed that leverage chemical and physical driving forces to overcome this challenging equilibrium. Alongside this strategy, enzyme engineering is typically required to develop TAs compatible with these non-physiological amine donors and the unnatural reaction conditions they require. We herein disclose N-phenylputrescine (NPP) as a readily accessible amine donor, inspired by the biosynthesis of the dipyrroloquinoline alkaloids. NPP is compatible with a broad range of synthetically useful TA biocatalysts and performs across an unparalleled variety of reaction conditions (pH and temperature). Synthetic applicability has been demonstrated through the synthesis of the anti-diabetic drug sitagliptin, delivering the product in excellent enantiopurity using just two equivalents of NPP<br>

scholarly journals N-Phenylputrescine (NPP): A Natural Product Inspired Amine Donor for Biocatalysis.

2021 ◽  
Author(s):  
Catherine A McKenna ◽  
Maria Stiblarikova ◽  
Irene De Silvestro ◽  
Dominic James Campopiano ◽  
Andrew L Lawrence
Keyword(s):  
Chemical Synthesis ◽  
Natural Product ◽  
Chiral Amines

The synthesis of chiral amines in enantioenriched form is a keystone reaction in applied chemical synthesis. There is a strong push to develop greener and more sustainable alternatives to the...

scholarly journals Applications of the Horner-Wadsworth-Emmons olefination in modern natural product synthesis

Synthesis ◽  
2021 ◽  
Author(s):  
Dávid Roman ◽  
Maria Sauer ◽  
Christine Beemelmanns
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Natural Product Synthesis ◽  
Reaction Conditions ◽  
Comprehensive Review ◽  
Modern Natural ◽  
Key Steps ◽  
Synthetic Approaches

Here, we have summarized more than 30 representative natural product syntheses published in 2015 to 2020 that employ one or more Horner-Wadsworth-Emmons (HWE) reactions. We comprehensively describe the applied phosphonate reagents, HWE reaction conditions and key steps of the total synthetic approaches. Our comprehensive review will support future synthetic approaches and serve as guideline to find the best HWE conditions for the most complicated natural products known

scholarly journals Intermolecular 3+3 Ring Expansion of Aziridines to Dehydropiperidines through the Intermediacy of Aziridinium Ylides

2019 ◽  
Author(s):  
Jennifer Schomaker ◽  
Josephine Eshon ◽  
Kate A. Nicastri ◽  
Steven C. Schmid ◽  
William T. Raskopf ◽  
...  
Keyword(s):  
Natural Product ◽  
Functional Group ◽  
Ring Expansion ◽  
Sigmatropic Rearrangement ◽  
Reactive Intermediate ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Complex Molecules ◽  
Form Complex ◽  
Reaction Proceeds

Bicyclic aziridines undergo formal [3+3] ring expansion reactions when exposed to rhodium-bound vinyl carbenes to form complex dehydropiperidines in a highly stereocontrolled rearrangement. Mechanistic studies and DFT computations indicate the reaction proceeds through the formation of a vinyl aziridinium ylide; this reactive intermediate undergoes a concerted, asynchronous, pseudo-[1,4]- sigmatropic rearrangement to directly furnish the heterocyclic products with net retention at the new C-C bond. In combination with an asymmetric silver-catalyzed aziridination developed in our group, this method quickly delivers enantioenriched scaffolds with up to three contiguous stereocenters. The mild reaction conditions, functional group tolerance, and high stereochemical retention of this method are especially well-suited for appending piperidine motifs to natural product and complex molecules. Ultimately, our work establishes the value of underutilized aziridinium ylides as key intermediates in strategies to convert small, strained rings to larger N-heterocycles.

scholarly journals Application of enzyme engineering in pharmacy

2020 ◽  
Vol 9 (2) ◽  
Author(s):  
Qiaole Li ◽  
Yanhong Li ◽  
Haoran Niu
Keyword(s):  
High Efficiency ◽  
Development Trend ◽  
Enzyme Engineering ◽  
Reaction Conditions ◽  
Important Method ◽  
Reaction Specificity ◽  
Prevention And Treatment ◽  
Modern Biotechnology ◽  
Catalytic Functions ◽  
The Development Trend

Enzyme engineering is an important part of modern biotechnology. Due to its high reaction specificity, high efficiency, mild reaction conditions, and low pollution, it is also an important method widely used in the pharmaceutical field. The application of enzymes in medicine is diverse, such as: diagnosis, prevention and treatment of diseases with enzymes, manufacture of various drugs with enzymes, etc., mainly through manual operations, to obtain enzymes required by the pharmaceutical industry, and through various means Enzymes perform their catalytic functions. This article mainly introduces the application of enzyme engineering in the pharmaceutical field, and also prospects the development trend of enzyme engineering in the pharmaceutical field.

Nanostructured Mg–Al Hydrotalcite as Catalyst for Fine Chemical Synthesis

2014 ◽  
Vol 14 (2) ◽  
pp. 1931-1946 ◽  
Author(s):  
Sulaiman N. Basahel ◽  
Shaeel A. Al-Thabaiti ◽  
Katabathini Narasimharao ◽  
Nesreen S. Ahmed ◽  
Mohamed Mokhtar
Keyword(s):  
Chemical Synthesis ◽  
Fine Chemical

Recent Applications of Alkene Metathesis in Fine Chemical Synthesis

2010 ◽  
pp. 207-274 ◽  
Author(s):  
Dario Bicchielli ◽  
Yannick Borguet ◽  
Lionel Delaude ◽  
Albert Demonceau ◽  
Ileana Dragutan ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Fine Chemical

scholarly journals Enzymatic Bioreactors: An Electrochemical Perspective

Catalysts ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1232
Author(s):  
Simin Arshi ◽  
Mehran Nozari-Asbemarz ◽  
Edmond Magner
Keyword(s):  
Direct Electron Transfer ◽  
High Surface ◽  
High Surface Area ◽  
Enzyme Engineering ◽  
Future Perspective ◽  
Enzymatic System ◽  
Reaction Conditions ◽  
Flow Reactors ◽  
Recent Developments ◽  
Enzyme Cascades

Biocatalysts provide a number of advantages such as high selectivity, the ability to operate under mild reaction conditions and availability from renewable resources that are of interest in the development of bioreactors for applications in the pharmaceutical and other sectors. The use of oxidoreductases in biocatalytic reactors is primarily focused on the use of NAD(P)-dependent enzymes, with the recycling of the cofactor occurring via an additional enzymatic system. The use of electrochemically based systems has been limited. This review focuses on the development of electrochemically based biocatalytic reactors. The mechanisms of mediated and direct electron transfer together with methods of immobilising enzymes are briefly reviewed. The use of electrochemically based batch and flow reactors is reviewed in detail with a focus on recent developments in the use of high surface area electrodes, enzyme engineering and enzyme cascades. A future perspective on electrochemically based bioreactors is presented.

scholarly journals Parallel Interconnected Kinetic Asymmetric Transformation (PIKAT) with an Immobilized ω-Transaminase in Neat Organic Solvent

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2140 ◽  
Author(s):  
Wesley Böhmer ◽  
Lucien Koenekoop ◽  
Timothée Simon ◽  
Francesco G. Mutti
Keyword(s):  
Kinetic Resolution ◽  
Enantiomeric Excess ◽  
Molar Ratio ◽  
Chiral Amines ◽  
Aqueous Environment ◽  
Chiral Amine ◽  
Parallel Kinetic Resolution ◽  
Pharmaceutical Manufacture ◽  
Prochiral Ketones ◽  
Asymmetric Transformation

Comprising approximately 40% of the commercially available optically active drugs, α-chiral amines are pivotal for pharmaceutical manufacture. In this context, the enzymatic asymmetric amination of ketones represents a more sustainable alternative than traditional chemical procedures for chiral amine synthesis. Notable advantages are higher atom-economy and selectivity, shorter synthesis routes, milder reaction conditions and the elimination of toxic catalysts. A parallel interconnected kinetic asymmetric transformation (PIKAT) is a cascade in which one or two enzymes use the same cofactor to convert two reagents into more useful products. Herein, we describe a PIKAT catalyzed by an immobilized ω-transaminase (ωTA) in neat toluene, which concurrently combines an asymmetric transamination of a ketone with an anti-parallel kinetic resolution of an amine racemate. The applicability of the PIKAT was tested on a set of prochiral ketones and racemic α-chiral amines in a 1:2 molar ratio, which yielded elevated conversions (up to >99%) and enantiomeric excess (ee, up to >99%) for the desired products. The progress of the conversion and ee was also monitored in a selected case. This is the first report of a PIKAT using an immobilized ωTA in a non-aqueous environment.

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