Tandem One-Pot Biocatalytic Oxidation and Wittig Reaction in Water.

We explore biocatalytic aldehyde generation under aqueous conditions, concomitantly delivering access to a one-pot Wittig reaction using stabilized phosphoranes and granting diverse alkene products. Using a recombinant choline oxidase mutant, we first undertake biocatalytic alcohol oxidation across a range of functional aliphatic primary alcohols, demonstrating a remarkable substrate tolerance for this enzyme, including chloride, bromide, azide, -methyl, and alkynyl groups. Following this, we extend capability and deliver a practicable milligram-scale one-pot Wittig reaction in water.

Accessing Active Fragments for Drug Discovery Utilising Nitroreductase Biocatalysis.

Biocatalysis has played a limited role in the early stages of drug discovery. This is often attributed to the limited substrate scope of enzymes not affording access to vast areas of novel chemical space. Here, we have shown a promiscuous nitroreductase enzyme (NR-55) can be used to produce a panel of functionalised anilines from a diverse panel of aryl nitro starting materials.

Harnessing a Biocatalyst to Bioremediate the Purification of Alkylglycosides.

As the world moves towards net-zero carbon emissions, the development of sustainable chemical manufacturing processes is essential. Within manufacturing, purification by distillation is often used, however this process is energy intensive and methods that could obviate or reduce its use are desirable. Developed herein is an alternative, oxidative biocatalytic approach that enables purification of alkyl monoglucosides (essential bio-based surfactant components).

RetroBioCat Database: A Platform for Collaborative Curation and Automated Meta-Analysis of Biocatalysis Data.

Despite the increasing use of biocatalysis for organic synthesis, there are currently no databases that adequately capture synthetic biotransformations. The lack of a biocatalysis database prevents accelerating biocatalyst characterization efforts from being leveraged to quickly identify candidate enzymes for reactions or cascades, slowing their development. The RetroBioCat Database (available at retrobiocat.

Realizing the Continuous Chemoenzymatic Synthesis of Anilines Using an Immobilized Nitroreductase.

The use of biocatalysis for classically synthetic transformations has seen an increase in recent years, driven by the sustainability credentials bio-based approaches can offer the chemical industry. Despite this, the biocatalytic reduction of aromatic nitro compounds using nitroreductase biocatalysts has not received significant attention in the context of synthetic chemistry. Herein, a nitroreductase (NR-55) is demonstrated to complete aromatic nitro reduction in a continuous packed-bed reactor for the first time.

One-Pot Chemoenzymatic Cascade for the Enantioselective C(1)-Allylation of Tetrahydroisoquinolines.

Herein, we report a one-pot, chemoenzymatic process for the synthesis of enantioenriched C(1)-allylated tetrahydroisoquinolines. This transformation couples a monoamine oxidase (MAO-N)-catalyzed oxidation with a metal catalyzed allylboration, followed by a biocatalytic deracemization to afford allylic amine derivatives in both high yields and good to high enantiomeric excess. The cascade is operationally simple, with all components added at the start of the reaction and can be used to generate key building blocks for further elaboration.

Biocatalytic Approaches to Building Blocks for Enzymatic and Chemical Glycan Synthesis.

While the field of biocatalysis has bloomed over the past 20-30 years, advances in the understanding and improvement of carbohydrate-active enzymes, in particular, the sugar nucleotides involved in glycan building block biosynthesis, have progressed relatively more slowly. This perspective highlights the need for further insight into substrate promiscuity and the use of biocatalysis fundamentals (rational design, directed evolution, immobilization) to expand substrate scopes toward such carbohydrate building block syntheses and/or to improve enzyme stability, kinetics, or turnover. Further, it explores the growing premise of using biocatalysis to provide simple, cost-effective access to stereochemically defined carbohydrate materials, which can undergo late-stage chemical functionalization or automated glycan synthesis/polymerization.

Oxidase enzymes as sustainable oxidation catalysts.

Oxidation is one of the most important processes used by the chemical industry. However, many of the methods that are used pose significant sustainability and environmental issues. Biocatalytic oxidation offers an alternative to these methods, with a now significant enzymatic oxidation toolbox on offer to chemists.

Advances in biocatalytic and chemoenzymatic synthesis of nucleoside analogues.

Introduction: Nucleoside analogues represent a cornerstone of achievement in drug discovery, rising to prominence particularly in the fields of antiviral and anticancer discovery over the last 60 years. Traditionally accessed using chemical synthesis, a paradigm shift to include the use of biocatalytic synthesis is now apparent.

Areas Covered: Herein, the authors discuss the recent advances using this technology to access nucleoside analogues.

Reaching New Biocatalytic Reactivity Using Continuous Flow Reactors.

The use of flow reactors in biocatalysis has increased significantly in recent years. Chemists have begun to design flow systems that even allow new biocatalytic reactions to take place. This concept article will focus on the design of flow systems that have allowed enzymes to go beyond their limits in batch.

Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases.

Chiral primary amines are important intermediates in the synthesis of pharmaceutical compounds. Fungal reductive aminases (RedAms) are NADPH-dependent dehydrogenases that catalyse reductive amination of a range of ketones with short-chain primary amines supplied in an equimolar ratio to give corresponding secondary amines. Herein we describe structural and biochemical characterisation as well as synthetic applications of two RedAms from spp.

Is it time for biocatalysis in fragment-based drug discovery?

The use of biocatalysts for fragment-based drug discovery has yet to be fully investigated, despite the promise enzymes hold for the synthesis of poly-functional, non-protected small molecules. Here we analyze products of the biocatalysis literature to demonstrate the potential for not only fragment generation, but also the enzyme-mediated elaboration of these fragments. Our analysis demonstrates that biocatalytic products can readily populate 3D chemical space, offering diverse catalytic approaches to help generate new, bioactive molecules.

One-Pot Synthesis of Chiral N-Arylamines by Combining Biocatalytic Aminations with Buchwald-Hartwig N-Arylation.

The combination of biocatalysis and chemo-catalysis increasingly offers chemists access to more diverse chemical architectures. Here, we describe the combination of a toolbox of chiral-amine-producing biocatalysts with a Buchwald-Hartwig cross-coupling reaction, affording a variety of α-chiral aniline derivatives. The use of a surfactant allowed reactions to be performed sequentially in the same flask, preventing the palladium catalyst from being inhibited by the high concentrations of ammonia, salts, or buffers present in the aqueous media in most cases.

Natural heterogeneous catalysis with immobilised oxidase biocatalysts.

The generation of immobilised oxidase biocatalysts allowing multifunctional oxidation of valuable chemicals using molecular oxygen is described. Engineered galactose oxidase (GOase) variants M and M, an engineered choline oxidase (AcCO6) and monoamine oxidase (MAO-N D9) displayed long-term stability and reusability over several weeks when covalently attached on a solid support, outperforming their free counterparts in terms of stability (more than 20 fold), resistance to heat at 60 °C, and tolerance to neat organic solvents such as hexane and toluene. These robust heterogenous oxidation catalysts can be recovered after each reaction and be reused multiple times for the oxidation of different substrates.

Radical-mediated direct C-H amination of arenes with secondary amines.

Aryl dialkyl amines, valuable subunits of a wide range of effect chemicals, are accessed by intramolecular amination of aromatic C-H bonds employing UV photolysis of -chloroamines. The reactions show good functional group tolerance and allow access to a range of fused and bridged polycyclic structures. The homogeneous reaction conditions allow for the one-pot conversion of secondary amines to their arylated derivatives.

Imine Reductases, Reductive Aminases, and Amine Oxidases for the Synthesis of Chiral Amines: Discovery, Characterization, and Synthetic Applications.

Synthesis of the chiral amine moiety is a key challenge for synthetic organic chemistry due to its prevalence in many biologically active molecules. Imine reductase and amine oxidase enzymes have enabled the biocatalytic synthesis of a host of chiral amine compounds. In this chapter, procedures for the synthesis of chiral amines using imine reductases (IREDs), the recently discovered IRED homologues reductive aminases, and amine oxidases (AOs) are described.

Highly Productive Oxidative Biocatalysis in Continuous Flow by Enhancing the Aqueous Equilibrium Solubility of Oxygen.

We report a simple, mild, and synthetically clean approach to accelerate the rate of enzymatic oxidation reactions by a factor of up to 100 when compared to conventional batch gas/liquid systems. Biocatalytic decomposition of H O is used to produce a soluble source of O directly in reaction media, thereby enabling the concentration of aqueous O to be increased beyond equilibrium solubility under safe and practical conditions. To best exploit this method, a novel flow reactor was developed to maximize productivity (g product L  h ).

Synthesis and organogelating behaviour of amino acid-functionalised triphenylenes.

Four novel amino acid-functionalised triphenylenes have been prepared with glycine, l-alanine, l-phenylalanine and l-tryptophan ethyl ester side-chains. The glycine derivative is a good gelator of chloroform, the alanine derivative gels ethanol and toluene, and the phenylalanine derivative gels benzene and toluene. The tryptophan derivative does not gel any of the solvents tested, most probably due to its more bulky structure, but forms microspheres by evaporation-induced self-assembly.