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Amino acids are a class of compounds with wide-ranging applications. The synthesis of amino acids from biomass-derived α-keto acids and ammonia is a sustainable way but the unstable primary imine intermediates (R-C=NH) easily form oligomers. Herein, targeting this problem, alkaline modified mesoporous silica was employed as a support for ruthenium (Ru/M-MCM-41), which could be used as a bifunctional catalyst in the reductive amination of α-keto acids to synthesize α-amino acids. The incorporation of Sr improved the dispersion of Ru nanoparticles and enhanced metal-support interactions via electron transfer from Sr to Ru, and the active Ru sites could efficiently hydrogenate primary imine intermediates to α-amino acids, thus prohibiting the formation of oligomers. Moreover, the Sr-dopant introduces base sites that could catalyze the hydrolysis of oligomers back to primary imine intermediates and finally hydrogenated to α-amino acids. As a result, >99 % yield of glycine was achieved from glyoxylic acid over Ru/Sr-MCM-41, which is nearly three times that achieved over Ru/MCM-41 (32.2 %)., (© 2024 Wiley-VCH GmbH.)

The access to the enantiopure noncanonical amino acid l-phosphinothricin (l-PPT) by applying biocatalysts is highly appealing in organic chemistry. In this study, a NADH-dependent glutamate dehydrogenase from Lachnospiraceae bacterium ( Lb GluDH) was chosen for the asymmetric synthesis of l-PPT. Three flexible loops undergoing big conformational shifts during the catalysis were identified and rationally engineered following the initial mutagenesis. The enzyme's specific activity toward the key precursor of l-PPT, 2-oxo-4-[(hydroxy) (methyl) phosphinyl] butyric acid (PPO), was improved from negligible to 9 U/mg, and the K m value was reduced to 17 mM. The computational analysis showed that the modified loops broadened the enzyme's narrow tunnels, allowing the substrate to access the binding pocket and get closer to the crucial residue D165, thereby enhancing the catalytic process. Utilizing the variant as the catalyst, the preparation of l-PPT achieved a 100% conversion rate within 60 min, coupled with a stereoselectivity exceeding 99.9%, demonstrating its practical capacity for industrial application. Similar enhancement in catalytic activity was obtained applying the same strategy to a typical NADH-dependent GluDH from Pyrobaculum islandicum ( Pis GluDH), indicating the effectiveness of our strategy for the protein engineering of GluDHs targeted to the biosynthesis of unnatural compounds.

During the deamination and amination processes of meso-diaminopimelate dehydrogenase (meso-DAPDH) from Symbiobacterium thermophilum (StDAPDH), residue R71 was observed to display distinct functions. H154 has been proposed as a basic residue that facilitates water molecules to attack the D-chiral carbon of meso-DAP during deamination. Inspired by the phenomenon of R71, the effects of H154 during deamination and amination were investigated in this study with the goal of enhancing the amination activities of StDAPDH. Single site saturation mutagenesis indicated that almost all of the H154 mutants completely lost their deamination activity towards meso-DAP. However, some H154 variants showed enhanced k cat /K m values towards pyruvic acid and other bulky 2-keto acids, such as 2-oxovaleric acid, 4-methyl-2-oxopentanoic acid, 2-ketobutyric acid, and 3-methyl-2-oxobutanoic acid. When combined with the previously reported W121L/H227I mutant, triple mutants with significantly improved k cat /K m values (2.4-, 2.5-, 2.5-, and 4.0-fold) towards these 2-keto acids were obtained. Despite previous attempts, mutations at the H154 site did not yield the desired results. Moreover, this study not only recognizes the distinctive impact of H154 on both the deamination and amination reactions, but also provides guidance for further high-throughput screening in protein engineering and understanding the catalytic mechanism of StDAPDH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Earth abundant metal-based heterogeneous catalysts with highly active and at the same time stable isolated metal sites constitute a key factor for the advancement of sustainable and cost-effective chemical synthesis. In particular, the development of more practical, and durable iron-based materials is of central interest for organic synthesis, especially for the preparation of chemical products related to life science applications. Here, we report the preparation of Fe-single atom catalysts (Fe-SACs) entrapped in N-doped mesoporous carbon support with unprecedented potential in the preparation of different kinds of amines, which represent privileged class of organic compounds and find increasing application in daily life. The optimal Fe-SACs allow for the reductive amination of a broad range of aldehydes and ketones with ammonia and amines to produce diverse primary, secondary, and tertiary amines including N-methylated products as well as drugs, agrochemicals, and other biomolecules (amino acid esters and amides) utilizing green hydrogen., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The reductive amination of 1,6-hexanediol with ammonia is one of the most promising green routes for synthesis of 1,6-hexanediamine. Herein, we developed a phosphorous modified Ni catalyst of Ni-P/Al 2 O 3 . It presented satisfactory improved selectivity to 1,6-hexanediamine in the reductive amination of 1,6-hexanediol compared to the Ni/Al 2 O 3 catalyst. The phosphorous tended to interact with Al 2 O 3 to form AlPO x species, induced Ni nanoparticle to be flatter, and the decrease of strong acid sites, the new-formed Ni-AlPO x -Al 2 O 3 interface and the flatter Ni nanoparticle were the key to switch the dominating product from hexamethyleneimine to 1,6-hexanediamine. This work develops an efficient catalyst for production of 1,6-hexanediamine from the reductive amination of 1,6-hexanediol, and provides a point of view about designing selective non-noble metal catalysts for producing primary diamines via reductive amination of diols., (© 2024 Wiley-VCH GmbH.)

The carbonyl functionality of natural organic matter (NOM) is poorly constrained. Here, we treated Suwannee River NOM (SRNOM) with ammonium acetate and sodium cyanoborohydride to convert ketone-containing compounds by reductive amination to their corresponding primary amines. The total dissolved nitrogen content increased by up to 275% after amination. Up to 30% of the molecular formulas of SRNOM contained isomers with ketone functionalities as detected by ultrahigh-resolution mass spectrometry. Most of these isomers contained one or two keto groups. At least 3.5% of the oxygen in SRNOM was bound in ketone moieties. The conversion of reacted compounds increased linearly with O/H values of molecular formulas and was predictable from the elemental composition. The mean conversion rate of reacted compounds nearly followed a log-normal distribution. This distribution and the predictability of the proportion of ketone-containing isomers solely based on the molecular formula indicated a stochastic distribution of ketones across SRNOM compounds. We obtained isotopically labeled amines by using 15 N-labeled ammonium acetate, facilitating the identification of reaction products and enabling NMR spectroscopic analysis. 1 H, 15 N HSQC NMR experiments of derivatized samples containing less than 20 μg of nitrogen confirmed the predominant formation of primary amines, as expected from the reaction pathway.

Enzymatic processes play an increasing role in synthetic organic chemistry which requires the access to a broad and diverse set of enzymes. Metagenome mining is a valuable and efficient way to discover novel enzymes with unique properties for biotechnological applications. Here, we report the discovery and biocatalytic characterization of six novel metagenomic opine dehydrogenases from a hot spring environment (mODHs) (EC 1.5.1.X). These enzymes catalyze the asymmetric reductive amination between an amino acid and a keto acid resulting in opines which have defined biochemical roles and represent promising building blocks for pharmaceutical applications. The newly identified enzymes exhibit unique substrate specificity and higher thermostability compared to known examples. The feature that they preferably utilize negatively charged polar amino acids is so far unprecedented for opine dehydrogenases. We have identified two spatially correlated positions in their active sites that govern this substrate specificity and demonstrated a switch of substrate preference by site-directed mutagenesis. While they still suffer from a relatively narrow substrate scope, their enhanced thermostability and the orthogonality of their substrate preference make them a valuable addition to the toolbox of enzymes for reductive aminations. Importantly, enzymatic reductive aminations with highly polar amines are very rare in the literature. Thus, the preparative-scale enzymatic production, purification, and characterization of three highly functionalized chiral secondary amines lend a special significance to our work in filling this gap. KEY POINTS: • Six new opine dehydrogenases have been discovered from a hot spring metagenome • The newly identified enzymes display a unique substrate scope • Substrate specificity is governed by two correlated active-site residues., (© 2024. The Author(s).)

Enzymatic functionalization of oligosaccharides is a useful and environmentally friendly way to expand their structural chemical space and access to a wider range of applications in the health, food, feed, cosmetics and other sectors. In this work, we first tested the laccase/TEMPO system to generate oxidized forms of cellobiose and methyl β-D-cellobiose, and obtained high yields of novel anionic disaccharides (>60 %) at pH 6.0. Laccase/TEMPO system was then applied to a mix of cellooligosaccharides and to pure D-cellopentaose. The occurrence of carbonyl and carboxyl groups in the oxidation products was shown by LC-HRMS, MALDI-TOF and reductive amination of the carbonyl groups was attempted with p-toluidine a low molar mass amine to form the Schiff base, then reduced by 2-picoline borane to generate a more stable amine bond. The new grafted products were characterized by LC-HRMS, LC-UV-MS/MS and covalent grafting was evidenced. Next, the same procedure was adopted to successfully graft a dye, the rhodamine 123, larger in size than toluidine. This two-step chemo-enzymatic approach, never reported before, for functionalization of oligosaccharides, offers attractive opportunities to anionic cellooligosaccharides and derived glucoconjugates of interest for biomedical or neutraceutical applications. It also paves the way for more environmentally-friendly cellulose fabric staining procedures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Catalyst development for upgrading bio-based chemicals towards primary amines has increasingly attracted owing to their applications in the pharmaceutical and polymer industries. The surface acidic sites in metal oxide-based catalysts play a key role in the reductive amination of aldehydes/ketones involving H 2 and NH 3 ; however, the crucial role of the type of surface acidic species and their strength remains unclear. Herein, this study exhibits the catalytic reductive amination of furfural (FUR) to furfurylamine (FUA) with Ru supported on tetragonal (Ru/T-ZrO 2 ) and monoclinic (Ru/M-ZrO 2 ) ZrO 2 . Ru/T-ZrO 2 exhibited an 11.8-fold higher rate of reductive amination than Ru/M-ZrO 2 , giving a quantitative yield of FUA (99 %) at 80 °C in 2.5 h and is recyclable up to four runs. Catalyst surface investigation using spectroscopic techniques, like X-ray photoelectron, electron paramagnetic resonance, and Raman, confirm higher oxygen vacancy sites (1.6 times) on the surface of Ru/T-ZrO 2 compared to Ru/M-ZrO 2 . Moreover, in-situ NH 3 -diffuse reflectance infrared Fourier transform spectroscopy studies display that Ru/T-ZrO 2 has more moderate Bronsted acidic sites (surface H-bonded hydroxyl groups) than Ru/M-ZrO 2 . Further, the controlled experiments and poisoning studies with KSCN and 2,6-lutidine suggest the crucial role of O v sites (Lewis acidic sites) and surface hydroxyl groups (Bronsted acidic sites) for selective FUA formation., (© 2024 Wiley-VCH GmbH.)

Polysaccharide-based nanogels offer a wide range of chemical compositions and are of great interest due to their biodegradability, biocompatibility, non-toxicity, and their ability to display pH, temperature, or enzymatic response. In this work, we synthesized monodisperse and tunable pH-sensitive nanogels by crosslinking, through reductive amination, chitosan and partially oxidized maltodextrins, by keeping the concentration of chitosan close to its overlap concentration, i.e. in the dilute and semi-dilute regime. The chitosan/maltodextrin nanogels presented sizes ranging from 63 ± 9 to 279 ± 16 nm, showed quasi-spherical and cauliflower-like morphology, reached a ζ-potential of +36 ± 2 mV and maintained a colloidal stability for up to 7 weeks. It was found that the size and surface charge of nanogels depended both on the oxidation degree of maltodextrins and chitosan concentration, as well as on its degree of acetylation and protonation, the latter tuned by pH. The pH-responsiveness of the nanogels was evidenced by an increased size, owed to swelling, and ζ-potential when pH was lowered. Finally, maltodextrin-chitosan biocompatible nanogels were assessed by cell viability assay performed using the HEK293T cell line., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

1,4-Diazepane-6-amine (DAZA) can be alkylated with three 2-hydroxybenzyl pendant arms, resulting in hexadentate chelators suitable for coordination of radiometals like 68 Ga. These chelators, N ,1,4-tri(alkoxy-2-hydroxybenzyl)-DAZA, can be produced via a one-pot synthesis, with the first step being a carbonyl amine condensation of DAZA with two respective 4-alkoxy-2-hydroxybenzaldehydes, followed by reductive amination with sodium borohydride. While the first step of this reaction is predictable, the subsequent reductive amination can result in either mono-, di- or tri(alkoxy-hydroxybenzyl)-DAZA compounds. Seeking to identify dependencies that might allow a specific reaction control towards the formation of either of the three possible products, and particularly towards the favoured trialkylated DAZA compounds, a variety of synthesis trials were performed. Additionally, computational methods were employed to evaluate the underlying reaction mechanism. Synthesis trials verified that the trialkylated DAZA compounds are formed via direct reductive amination of the dialkylated DAZA compounds. Subsequently, a synthetic method was established, leading to an increase in the percentage of the trialkylated DAZA compounds, which allowed the successful isolation of those hexadentate chelators. Additionally, an alternative pathway proceeding via aminal C-N bond insertion of an attacking third carbonyl moiety was evaluated by means of quantum chemical calculations but so far remains entirely hypothetical., Competing Interests: M.F. and J.G. hold a patent on liver-specific chelators for radiometal nuclides based on the DAZA derivatives described in this article. All other authors declare no conflicts of interest., (© 2024 The Authors.)

Nitrogen-containing molecules are used for the synthesis of polymers, surfactants, agrochemicals, and dyes. In the context of green chemistry, it is important to form such compounds from bioresource. Short-chain primary amines are of interest for the polymer industry, like 2-aminopropanol, 1-aminopropan-2-ol, and 1,2-diaminopropane. These amines can be formed through the amination of oxygenated substrates, preferably in aqueous phase. This is possible with heterogeneous catalysts, however, effective systems that allow reactions under mild conditions are lacking. We report an efficient catalyst Ru-Ni/AC for the reductive amination of hydroxyacetone into 2-aminopropanol. The catalyst has been reused during 3 cycles demonstrating a good stability. As a prospective study, extension to the reactivity of (poly)carbohydrates has been realized. Despite a lesser efficiency, 2-aminopropanol (9 % yield of amines) has been formed from fructose, the first example from a carbohydrate. This was possible using a 7.5 %Ru-36 %W x C/AC catalyst, composition allowing a one-pot retro-aldol cleavage into hydroxyacetone and reductive amination. The transformation of cellulose through sequential reactions with a combination of 30 %W 2 C/AC and 7.5 %Ru-36 %W x C/AC system gave 2 % of 2-aminopropanol, corresponding to the first example of the formation of this amine from cellulose with heterogeneous catalysts., (© 2024 Wiley-VCH GmbH.)

N -aryl-substituted pyrrolidines are important moieties widely found in bioactive substances and drugs. Herein, we present a practical reductive amination of diketones with anilines for the synthesis of N -aryl-substituted pyrrolidines in good to excellent yields. In this process, the N -aryl-substituted pyrrolidines were furnished via successive reductive amination of diketones via iridium-catalyzed transfer hydrogenation. The scale-up performance, water as a solvent, simple operation, as well as derivation of drug molecules showcased the potential application in organic synthesis.

A series of 23 novel benzylamines was synthesized by reductive amination from halogen-substituted 3- and 4-benzyloxybenzaldehyde derivatives and 6-methylhept-2-yl amine or n-octylamine. The antimycotic activity of the resulting amines was evaluated in a microdilution assay against the apathogenic yeast Yarrowia lipolytica as test microorganism. Promising compounds were also tested against human pathogenic Candida species. The influence of halogen substituents at the benzyl ether side chain was studied in this screening, as well as the influence of the branched side chain of (±)-6-methylhept-2-yl amine in comparison with the n-octyl side chain., (© 2024 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

DNA-encoded libraries (DELs) have become a leading technology for hit identification in drug discovery projects as large, diverse libraries can be generated. DELs are commonly synthesised via split-and-pool methodology; thus, chemical transformations utilised must be highly efficient, proceeding with high conversions. Reactions performed in DEL synthesis also require a broad substrate scope to produce diverse, drug-like libraries. Many pharmaceutical compounds incorporate multiple C-N bonds, over a quarter of which are synthesised via reductive aminations. However, few on-DNA reductive amination procedures have been developed. Herein is reported the application of the micelle-forming surfactant, TPGS-750-M, to the on-DNA reductive amination of DNA-conjugated amines, yielding highly efficient conversions with a broad range of aldehydes, including medicinally relevant heterocyclic and aliphatic substrates. The procedure is compatible with DNA amplification and sequencing, demonstrating its applicability to DEL synthesis., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Peptide drugs have disadvantages such as low stability, short half-life and side effects, which limit their widespread use in clinical practice. Therefore, peptide drugs can be modified to improve these disadvantages. Numerous studies have shown that alkyl-modified peptide drugs can self-assemble to prolong the duration of efficacy and/or reduce side effects. However, the commonly used solid-phase synthesis method for alkyl-modified peptides is time-consuming. To overcome this, a simple reductive amination reaction was employed, which can directly graft the alkyl chain to the peptide sequence and effectively avoid stepwise synthesis from C- to N-terminal with amino acids. In this study, ω-conotoxin MVIIA was used as the peptide drug, while myristic aldehyde was used as the alkylating agent. To obtain the maximum productivity of modified peptides, the molar ratio of peptide MVIIA to myristic aldehyde in the reductive amination reaction was optimized. Furthermore, the peptide modification sites in this reaction were confirmed by secondary mass spectrometry analysis. Besides, alkyl-modified peptide MVIIA was able to form micelles by self-assembly and improved stability in serum, which was related to our previous work where myristoylated peptide MVIIA micelles can improve the drug stability. Finally, this study was intended to provide a methodological basis for modifying the alkyl chain of peptide drugs., (© 2024. The Author(s).)

DNA encoded library (DEL) synthesis represents a convenient means to produce, annotate and store large collections of compounds in a small volume. While DELs are well suited for drug discovery campaigns, the chemistry used in their production must be compatible with the DNA tag, which can limit compound class accessibility. As a result, most DELs are heavily populated with peptidomimetic and sp 2 -rich molecules. Herein, we show that sp 3 -rich mono- and bicyclic heterocycles can be made on DNA from ketochlorohydrin aldol products through a reductive amination and cyclization process. The resulting hydroxypyrrolidines possess structural features that are desirable for DELs and target a distinct region of pharmaceutically relevant chemical space., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

( R )-Homobenzylic amines are key structural motifs present in ( R )-selegiline, a drug indicated for the treatment of early-stage Parkinson's disease. Herein, we report a new short chemoenzymatic approach (in 2 steps) towards the synthesis of ( R )-selegiline via stereoselective biocatalytic reductive amination as the key step. The imine reductase IR36-M5 mutant showed high conversion (97%) and stereoselectivity (97%) toward the phenylacetone and propargyl amine substrates, offering valuable biocatalysts for synthesizing alkylated homobenzylic amines.

Catalytic hydrogenation of nitriles represents an efficient and sustainable one-step synthesis of valuable bulk and fine chemicals. We report herein a molecular cobalt electrocatalyst for selective hydrogenative coupling of nitriles with amines using protons as the hydrogen source. The key to success for this reductive reaction is the use of an electrocatalytic approach for efficient cobalt-hydride generation through a sequence of cathodic reduction and protonation. As only electrons (e - ) and protons (H + ) as the redox equivalent and hydrogen source, this general electrohydrogenation protocol is showcased by highly selective and straightforward synthesis of various functionalized and structurally diverse amines, as well as deuterium isotope labeling applications. Mechanistic studies reveal that the electrogenerated cobalt-hydride transfer to nitrile process is the rate-determining step., (© 2023 Wiley-VCH GmbH.)

Formamides are important feedstocks for the manufacture of many fine chemicals. State-of-the-art synthesis of formamides relies on the use of an excess amount of reagents, giving copious waste and thus poor atom-economy. Here, we report the first example of direct synthesis of N-formamides by coupling two challenging reactions, namely reductive amination of carbonyl compounds, particularly biomass-derived aldehydes and ketones, and fixation of CO 2 in the presence of H 2 over a metal-organic framework supported ruthenium catalyst, Ru/MFM-300(Cr). Highly selective production of N-formamides has been observed for a wide range of carbonyl compounds. Synchrotron X-ray powder diffraction reveals the presence of strong host-guest binding interactions via hydrogen bonding and parallel-displaced π⋅⋅⋅π interactions between the catalyst and adsorbed substrates facilitating the activation of substrates and promoting selectivity to formamides. The use of multifunctional porous catalysts to integrate CO 2 utilisation in the synthesis of formamide products will have a significant impact in the sustainable synthesis of feedstock chemicals., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Cell therapy using endothelial cells (ECs) has great potential for the treatment of congenital disorders, such as hemophilia A. Cell sheet technology utilizing a thermoresponsive culture dish is a promising approach to efficiently transplant donor cells. In this study, a new method to prepare terminus-selective heparin-immobilized thermoresponsive culture surfaces is developed to facilitate the preparation of EC sheets. Alkynes are introduced to the reducing terminus of heparin via reductive amination. Cu-catalyzed azide-alkyne cycloaddition (CuAAC) facilitates efficient immobilization of the terminus of heparin on a thermoresponsive surface, resulting in a higher amount of immobilized heparin while preserving its function. Heparin-immobilized thermoresponsive surfaces prepared using CuAAC exhibit good adhesion to human endothelial colony-forming cells (ECFCs). In addition, upon further binding to basic fibroblast growth factor (bFGF) on heparin-immobilized surfaces, increased proliferation of ECFCs on the surface is observed. The confluent ECFC monolayer cultured on bFGF-bound heparin-immobilized thermoresponsive surfaces exhibits relatively high fibronectin accumulation and cell number and detaches at 22 °C while maintaining the sheet-like structure. Because heparin has an affinity for several types of bioactive molecules, the proposed method can be applied to facilitate efficient cultures and sheet formations of various cell types., (© 2023 Wiley-VCH GmbH.)

Valorization of biomass-derived polyols into high-value-added ethanolamines and ethylenediamines is highly attractive. Herein, we report a one-step photocatalytic protocol to convert bio-polyols into a 60 % yield of ethanolamines and ethylenediamines over a multifunctional Cu/TiO 2 catalyst. This catalyst enables a tandem process of photocatalytic polyol C-C bond cleavage and reductive amination in one pot at room temperature, and also allows the selective conversion of various bio-polyols and amines. Mechanistic studies revealed that photogenerated holes in TiO 2 promote the retro-aldol C-C bond cleavage or oxidative dehydrogenation of polyols, and photogenerated electrons accumulate on small-sized Cu clusters, which facilitate the reductive amination via hydrogen transfer and prevent the H 2 generation. This strategy provides new opportunities for the development of non-noble metal photocatalysts and methods of biomass conversion under mild conditions., (© 2023 Wiley-VCH GmbH.)

The large variety and high concentration of O-glycans are characteristic properties of mucins and play a crucial role in their unique functions. Analyzing the O-glycans of mucins is essential for investigating the functions of mucins. Eliminative oximation is an aqueous reaction that can be used to obtain O-glycan oximes from mucins. Using diazabicyclo undec-7ene (DBU) as a base, an organic superbase that can be removed with an organic solvent during solid-phase extraction, and adding hydroxylamine to the reaction mixture in advance, the O-glycans released from the mucin are immediately converted to the corresponding glycan oximes. The glycan oxime can then be fluorescently labeled with a fluorescent labeling reagent and 2-picoline borane via reductive amination. O-glycans that have been fluorescently labeled can be analyzed using conventional HPLC techniques., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Reductive amination is a relatively simple and convenient strategy for coupling purified polysaccharides to carrier proteins. Following their synthesis, glycoconjugates can be used to assess the protective capacity of specific microbial polysaccharides in animal models of infection and/or to produce polyclonal antiserum and monoclonal antibodies for a variety of immune assays. Here, we describe a reproducible method for chemically activating the 6-deoxyheptan capsular polysaccharide (CPS) from Burkholderia pseudomallei and covalently linking it to recombinant CRM197 diphtheria toxin mutant (CRM197) to produce the glycoconjugate, CPS-CRM197. Similar approaches can also be used to couple other types of polysaccharides to CRM197 with little to no modification of the protocol., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The piperazine moiety is often found in drugs or in bioactive molecules. This widespread presence is due to different possible roles depending on the position in the molecule and on the therapeutic class, but it also depends on the chemical reactivity of piperazine-based synthons, which facilitate its insertion into the molecule. In this paper, we take into consideration the piperazine-containing drugs approved by the Food and Drug Administration between January 2011 and June 2023, and the synthetic methodologies used to prepare the compounds in the discovery and process chemistry are reviewed.

Nowadays, the field of biomass conversion is gradually moving towards an encouraging stage. The preparation of nitrogen-containing chemicals using various biomass resources instead of fossil resources do not only reduce carbon emissions, but also diversify the products of biomass conversion, thus increasing the economic competitiveness of biomass refining systems. Levulinic acid (LA) can be used as a promising intermediate in biomass conversion for further synthesis of pyrrolidone via reductive amination. However, there are still many critical issues to be solved. Particularly, the specific effects of catalysts on the performance of LA reductive amination have not been sufficiently revealed, and the potential impacts of key conditional factors have not been clearly elucidated. In view of this, this review attempts to provide theoretical insights through an in-depth interpretation of the above key issues. The contribution of catalysts to the reductive amination of LA as well as the catalyst structural preferences for improving catalytic performance are discussed. In addition, the role of key conditional factors is discussed. The insights presented in this review will contribute to the design of catalyst nanostructures and the rational configuration of green reaction conditions, which may provide inspiration to facilitate the nitrogen-related transformation of more biomass platform molecules., (© 2023 Wiley-VCH GmbH.)

Opines and opine-type chemicals are valuable natural products with diverse biochemical roles, and potential synthetic building blocks of bioactive compounds. Their synthesis involves reductive amination of ketoacids with amino acids. This transformation has high synthetic potential in producing enantiopure secondary amines. Nature has evolved opine dehydrogenases for this chemistry. To date, only one enzyme has been used as biocatalyst, however, analysis of the available sequence space suggests more enzymes to be exploited in synthetic organic chemistry. This review summarizes the current knowledge of this underexplored enzyme class, highlights key molecular, structural, and catalytic features with the aim to provide a comprehensive general description of opine dehydrogenases, thereby supporting future enzyme discovery and protein engineering studies., (© 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Certified reference materials (CRM) of amphetamine derivatives were produced through a simple, rapid and efficient synthesis in both batch and continuous-flow conditions, accompanied by the development of a comprehensive certification protocol for this class of substances. Our chemistry enabled the synthesis of MDA, MDMA, PMA and PMMA in two steps from safrole and estragole with overall yields of 38-61 % in 48 hours under batch conditions and 61-65 % in 65 minutes under continuous-flow conditions, followed by the development of a certification protocol for these materials through identity checking, homogeneity, stability, and characterization studies. Furthermore, as result of this work, a very pure CRM of MDA.HCl with 99.1±1.4 g/100 g of certified characterization value was produced. Considering the importance of supplying amphetamine calibrants for public security efforts in Forensic Chemistry, the potential therapeutical applications, and responding to the rising demand for the synthesis of CRM, this work presents a pioneering approach for the production of amphetamine and related compounds., (© 2023 Wiley-VCH GmbH.)

The reductive amination of carbonyl compounds is one of the most straightforward protocols to construct C-N bonds, but highly desires active and selective catalysts. Herein, Pd/MoO 3-x catalysts are proposed for furfural amination, in which the interactions between Pd nanoparticles and MoO 3-x supports can be easily ameliorated by varying the preparation temperature toward efficient catalytic turnover. Thanks to the synergistic cooperation of Mo V -rich MoO 3-x and highly dispersed Pd, the optimal catalysts afford the high yield of furfurylamine (84 %) at 80 °C. Thereinto, Mo V species not only acts as the acidic promoter to facilitate the activation of carbonyl groups, but also interacts with Pd nanoparticles to promote the subsequent hydrogenolysis of Schiff base N-furfurylidenefurfurylamine and its germinal diamine. The good efficiency of Pd/MoO 3-x within a broad substrate scope further highlights the key contribution of metal-support interactions to the refinery of biomass feedstocks., (© 2023 Wiley-VCH GmbH.)

Homoallylic amines prepared via addition of allylsilanes often require preformed imine substrates, metal catalysts, fluoride activators, or use of protected amines. In this metal-free, air- and water-tolerant procedure, aromatic aldehyde and aniline substrates undergo direct alkylative amination using easily accessible 1-allylsilatrane., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Chiral amines are broadly used compounds in pharmaceutical industry and organic synthesis, and reductive amination reactions have been the most appreciated methods for their syntheses. However, one-step transfer hydrogenative direct asymmetric reductive amination (THDARA) that could expand the scope, simplify the operation and eliminate the use of additives has been challenging. In this work, based on the Xiao's racemic transfer hydrogenative reductive amination in 2010 and our recent work in novel chiral pyridine ligands, chiral half-sandwich iridium catalysts were rationally designed and synthesized. Using the optimized catalyst and azeotropic mixture of formic acid and triethylamine as the hydrogen source, a broad range of α-chiral (hetero)aryl amines, including various polar functional groups and heterocycles, were prepared in generally high yield and enantioselectivity under mild and operationally simple conditions. Density functional theory (DFT) calculation of the catalytically active Ir-H species and the key hydride transfer step supported the chiral pyridine-induced stereospecific generation of the iridium center, and the enantioselection by taming the highly flexible key transition structure with multiple attractive non-covalent interactions. This work introduced a type of effective chiral catalysts for simplified approach to medicinally important chiral amines, as well as a rare example of robust enantioselective transition-metal catalysis., (© 2023 Wiley-VCH GmbH.)

The atom- and step-efficient synthesis of chiral fused tricyclic lactams from readily available ketoesters using cheap ammonium salts as the nitrogen source is reported. This ruthenium-catalyzed system operates through an efficient tandem dynamic kinetic asymmetric reductive amination (ARA)/lactamization and produces chiral fused tricyclic lactams in high yields with excellent diastereo- and enantioselectivity (up to >99 % ee, >20 : 1 dr and 98 % yield). The robust method was also applied to the concise synthesis of key intermediates in the synthesis of rivastigmine analogues and chiral N-heterocyclic carbene catalysts., (© 2023 Wiley-VCH GmbH.)

Herein, we used isotopic formaldehyde and sodium cyanoborohydride via reductive amination to label two methyl groups on primary amine to arrange the standards ( h 2 -formaldehyde-modified) and internal standards (ISs, d 2 -formaldehyde-modified) of tryptophan and its metabolites, such as serotonin (5-hydroxytryptamine) and 5-hydroxytryptophan. These derivatized reactions with a high yield are very satisfactory for manufacturing standards and ISs. This strategy will generate one or two methyl groups on amine to create different mass unit shifts with 14 vs. 16 or 28 vs. 32 in individual compounds for biomolecules with amine groups. In other words, multiples of two mass units shift are created using this derivatized method with isotopic formaldehyde. Serotonin, 5-hydroxytryptophan, and tryptophan were used as examples to demonstrate isotopic formaldehyde-generating standards and ISs. h 2 -formaldehyde-modified serotonin, 5-hydroxytryptophan, and tryptophan are standards to construct calibration curves, and d 2 -formaldehyde-modified analogs such as ISs spike into samples to normalize the signal of each detection. We utilized multiple reaction monitoring modes and triple quadrupole mass spectrometry to demonstrate the derivatized method suitable for these three nervous biomolecules. The derivatized method demonstrated a linearity range of the coefficient of determinations between 0.9938 to 0.9969. The limits of detection and quantification ranged from 1.39 to 15.36 ng/mL.

Utilization of N,N-dimethylformamide (DMF) as an amine source and reductant for synthesizing tertiary amines is a promising way to replace the substrates formaldehyde and dimethylamine, and it is desirable to seek porous acid-resistant catalysts for heterogeneous catalysis of this reaction. Herein, a robust metal-organic framework (MOF) {[Th 6 O 4 (OH) 4 (H 2 O) 6 (BCP) 3 ]⋅10 DMF} n (1) containing stacked nanocages with a diameter of 1.55 nm was constructed. Compound 1 can maintain its single-crystal structure even kept in air at 400 °C for 3 h, and in DMF or water at 200 °C for 7 days. Density functional theory (DFT) calculations suggested that the high interaction energy between the [Th 6 O 4 (OH) 4 (H 2 O) 6 ] 12+ clusters and ligands was responsible for the excellent stability of 1. Catalytic investigations revealed that 1 can effectively and size-selectively catalyze the reductive amination of aldehydes with DMF, and it can be reused at least five times without obvious loss in catalytic activity., (© 2023 Wiley-VCH GmbH.)

Photodynamic therapy (PDT) has been used as an alternative or as a complement of conventional approaches for cancer treatment. In PDT, the reactive oxygen species (ROS) produced from the interaction between the photosensitizer (PS), visible light and molecular oxygen, kill malignant cells by triggering a cascade of cytotoxic reactions. In this process, the PS plays an extremely important role in the effectiveness of the therapy. In the present work, a new photoimmunoconjugate (PIC), based on cetuximab and the known third generation PS-glycophthalocyanine ZnPcGal 4, was synthesized via reductive amination. The rationale behind this was the simultaneous cancer-associated specific targeting of PIC and photosensitization of targeted receptor positive cells. Varied reaction parameters and photodynamic conditions, such as PS concentrations and both type and intensities of light, were optimized. ZnPcGal 4 showed significant photoactivity against EGFR expressing A431, EGFR-transfected HCT116 and HT29 cells when irradiated with white light of stronger intensity (38 mW/cm 2 ). Similarly, the synthesized PICs-T1 and T2 also demonstrated photoactivity with high intensity white light. The best optimized PIC: sample 28 showed no precipitation and aggregation when inspected visually and analyzed through SE-HPLC. Fluorescence excitation of sample 28 and 125 I-sample 28 radioconjugate ( 125 I-PIC, 125 I-radiolabeling yield ≥95%, determined with ITLC) at 660 nm showed presence of appended ZnPcGal 4 . In addition, simultaneous fluorescence and radioactivity detection of the 125 I-PIC in serum and PBS (pH 7.4) for the longest incubated time point of 72 h, respectively, and superimposed signals thereof demonstrated ≥99% of loading and/or labeling yield, assuring overall stability of the PIC and corresponding PIC-radioconjugate w.r.t. both the appended ZnPcGal 4 and bound- 125 I. Moreover, real-time binding analyses on EGFR-transfected HCT116 cells showed specific binding of 125 I-PIC, suggesting no alternation in the binding kinetics of the mAb after appending it with ZnPcGal 4 . These results suggest dual potential applications of synthesized PICs both for PDT and radio-immunotherapy of cancer., Competing Interests: Declaration of Competing Interest The authors have no relevant conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Direct asymmetric reductive amination of bio-based levulinic acid (LA) to the enantioenriched 5-methylpyrrolidinone is achieved by using a readily available chiral Ru/bisphosphine catalyst with excellent enantioselectivity (up to 96 % ee) and high isolated yield (up to 89 %). Methyl levulinate (ML), a byproduct from the industrial production of 2,5-furandicarboxylic acid (FDCA), can be used instead of LA with similar reactivity and selectivity. Mass spectrometry and isotope labelling studies indicate that the chiral lactam is formed via imine-enamine tautomerization/cyclization followed by asymmetric hydrogenation of the cyclic enamide., (© 2023 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Carbonyl compounds are mainly analysed by HPLC with ultraviolet detection after reaction with DNPH, yielding carbonyl-hydrazones. The presence of geometrical isomers whose relative abundance is dependent on the reaction condition introduces analytical errors and increases the complexity of the chromatograms. In this work, a simple, fast, and robust method for determining pyruvic acid, acetaldehyde, and α-ketobutyric acid in Port wines, dry table wines, and wine spirits by reductive amination of aldehyde 2,4-dinitrophenylhydrazones using cyanoborohydride followed by HPLC-DAD was developed, optimised and validated. The developed method was simple and showed good performance in several parameters such as linearity (0.025-200 mg/L), detection limits (0.0043-0.0097 mg/L), quantification (0.014-0.032 mg/L), precision (1.1-4.2 %) and accuracy (99.02 %). The method was applied to five different wine matrices, White, Tawny, and Ruby Port wines, white and red table wines, and wine spirits. The quantification of these carbonyl compounds simultaneously was achieved in Port wines for the first time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Simple unhindered aldimines tend to hydrolyze or oligomerize and are therefore spectroscopically not well characterized. Herein we report the formation and spectroscopic characterization of the simplest imino acid, namely glycine imine, by cryogenic matrix isolation IR and UV/Vis spectroscopy. Glycine imine forms after UV irradiation of 2-azidoacetic acid by N 2 extrusion in anti-(E,E)- and anti-(Z,Z)-conformation that can be photochemically interconverted. In matrix isolation pyrolysis experiments with 2-azidoacetic acid, glycine imine cannot be trapped as it further decarboxylates to aminomethylene. In aqueous solution glycine imine is hydrolyzed to hydroxy glycine and hydrated glyoxylic acid. At higher concentrations or in the presence of Fe II SO 4 as a reducing agent glycine imine undergoes self-reduction by oxidative decarboxylation chemistry. Glycine imine may be seen as one of the key reaction intermediates connecting prebiotic amino acid and sugar formation chemistry., (© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Microwave (MW)-assisted reductive aminations of aldehydes and ketones were carried out in the presence of commercial and homemade heterogeneous Rh-based catalysts. Ultrasound (US) was used to improve dispersion and stability of metal nanoparticles, while commercial activated carbon and carbon nanofibers were used as supports. Moreover, various bio-derived molecules were selected as substrates, and aqueous ammonia was used as a cheap and non-toxic reagent. MW combined with heterogeneous Rh catalysts gave a 98.2 % yield in benzylamine at 80 °C with 10 bar H 2 for 1 h; and a 43.3 % yield in phenylethylamine at 80 °C and 5 bar H 2 for 2 h. Carbon nanofibers proved to be a better support for the metal active phase than simple activated carbon, since a limited yield in benzylamine (10.6 %) but a high selectivity for the reductive amination of ketones was obtained. Thus, raspberry ketone was converted to raspberry amine in a 63.0 % yield., (© 2023 The Authors. ChemPlusChem published by Wiley-VCH GmbH.)

The design, synthesis, and initial study of amino-functionalized porphyrins as a new class of bifunctional catalysts for asymmetric organophotocatalysis is described. Two new types of amine-porphyrin hybrids derived from 5,10,15,20-tetraphenylporphyrin (TPPH 2 ), in which a cyclic secondary amine moiety is covalently linked either to a β-pyrrolic position (Type A) or to the p -position of one of the meso phenyl groups (Type B), were prepared by condensation, reductive amination, or amidation reactions from the suitable porphyrins (either formyl or methanamine derivatives) with readily available chiral amines. A preliminary study of the possible use of Type A amine-porphyrin hybrids as asymmetric, bifunctional organophotocatalysts was performed using the chiral, imidazolidinone-catalyzed Diels-Alder cycloaddition between cyclopentadiene 28 and trans -cinnamaldehyde 29 as a benchmark reaction. The yield and the stereochemical outcome of this process, obtained under purely organocatalytic conditions, under dual organophocatalysis, and under bifunctional organophotocatalysis, were compared.

N-(2-thioethyl)-2-aminobenzamide (TEAB), a novel glycan auxiliary, was synthesized and its utility was evaluated. The auxiliary was conjugated to glycans by reductive amination with the water-stable reagent 2-picoline borane complex. Glycan products, which ranged from 1 to 7 linked hexoses, were all isolated in yields ranging from 60% to 90% after purification by reverse-phase chromatography. The novel conjugate introduces a convenient, shelf-stable thiol directly onto the desired free glycans with purification advantages and direct modification with efficient reactions through alkenes, halides, epoxides, disulfides, and carboxylates in yields of 49% to 93%. Subsequently, a thiol-selective modification of the BSA protein was used to generate a neoglycoprotein with a bifunctional PEG-maleimide linker. To further illustrate the utility of a thiol motif, 2-thiopyridine activation of a thiol-containing support facilitated the covalent chromatographic purification of labeled glycans in yields up to 63%. Finally, initial proof of concept of implementation in a light printed microarray was explored and validated through FITC-labeled concanavalin A binding. In conclusion, the thiol-functionalized glycans produced greatly expand the diversity of bioconjugation tools that can be developed with glycans and enable a variety of biological investigations.

Imine reductases (IREDs) are NADPH-dependent enzymes with significant biocatalytic potential for the synthesis of primary, secondary, and tertiary chiral amines. Their applications include the reduction of cyclic imines and the reductive amination of prochiral ketones. In this study, twenty-nine novel IREDs were revealed through genome mining. Imine reductase activities were screened at pH 7 and 9 and in presence of either NADPH or NADH; some IREDs showed good activities at both pHs and were able to accept both cofactors. IREDs with Asn and Glu at the key 187 residue showed preference for NADH. IREDs were also screened against a series of dihydroisoquinolines to synthesise tetrahydroisoquinolines (THIQs), bioactive alkaloids with a wide range of therapeutic properties. Selected IREDs showed high stereoselectivity, as well high THIQ yields (>90 %) when coupled to a glucose-6-phosphate dehydrogenase for NADPH cofactor recycling., Competing Interests: None declared., (© 2022 The Authors. ChemCatChem published by Wiley-VCH GmbH.)

5-Hydroxymethylfurfural (5-HMF) represents a well-known class of lignocellulosic biomass-derived platform molecules. With the presence of many reactive functional groups in the structure, this versatile building block could be valorized into many value-added products. Among well-established catalytic transformations in biorefinery, the reductive amination is of particular interest to provide valuable N-containing compounds. Specifically, the reductive amination of 5-HMF with ammonia (NH 3 ) and molecular hydrogen (H 2 ) offers a straightforward and sustainable access to primary furanic amines [i. e., 5-hydroxymethyl-2-furfuryl amine (HMFA) and 2,5-bis(aminomethyl)furan (BAMF)], which display far-reaching utilities in pharmaceutical, chemical, and polymer industries. In the presence of heterogeneous catalysts contanining monometals (Ni, Co, Ru, Pd, Pt, and Rh) or bimetals (Ni-Cu and Ni-Mn), this elegant pathway enables a high-yielding and chemoselective production of HMFA/BAMF compared to other synthetic routes. This Review aims to present an up-to-date highlight on the supported metal-catalyzed reductive amination of 5-HMF with elaborate studies on the role of metal, solid support, and reaction parameters. Besides, the recyclability/adaptability of catalysts as well as the reaction mechanism are also provided to give valuable insights into this potential 5-HMF valorization strategy., (© 2022 Wiley-VCH GmbH.)

Chitin, the second most abundant biopolymer in the planet after cellulose, represents a renewable carbon and nitrogen source. A thrilling opportunity for the valorization of chitin is focused on the preparation of biomass-derived N -doped carbonaceous materials. In this contribution, chitin-derived N -doped carbons were successfully prepared and functionalized with palladium metal nanoparticles. The physicochemical properties of these nanocomposites were investigated following a multi-technique strategy and their catalytic activity in reductive amination reactions was explored. In particular, a biomass-derived platform molecule, namely furfural, was upgraded to valuable bi-cyclic compounds under continuous flow conditions.

Cobalt (Co) as a substitute of noble-metal catalysts shows high catalytic capability for production of the widely used primary amines through the reductive amination. However, the synthesis of Co catalysts usually involves the introduction of organic compounds and the high-temperature pyrolysis, which is complicated and difficult for large-scale applications. Herein, we demonstrated a facile and efficient strategy for the preparation of Co catalysts through the in situ reconstruction of cobalt borate (CoBO x ) during the reductive amination, delivering a high catalytic activity for production of benzylamine from benzaldehyde and ammonia. Initially, CoBO x was transformed into Co(OH) 2 through the interaction with ammonia and subsequently reduced to Co nanoparticles by H 2 under the reaction environments. The in situ generated Co catalysts exhibited a satisfactory activity and selectivity to the target product, which overmatched the commonly used Co/C, Pt or Raney Ni catalysts. We anticipate that such an in situ reconstruction of CoBO x by reactants during the reaction could provide a new approach for the design and optimization of catalysts to produce primary amines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Zhang and Ma.)

The feasibility of on-capillary derivatization of saccharides by aromatic amine-based fluorescent labeling agents was tested. To avoid the problematic evolution of gaseous hydrogen cyanide, the Schiff base reduction by sodium cyanoborohydride, as the second step of the standard reductive amination protocol, was omitted. Glucose was used as a model analyte and 7-amino-1,3-naphthalenedisulfonic acid as the labeling agent. Our experiments showed that the direct reaction of the saccharide with the labeling agent in 2.5-M acetic acid yields a labeled product that is sufficiently stable to be separated from the labeling agent in 20-mM phosphate buffer, pH 3.5, and detected using UV detection. The glucose and label zones were introduced separately into the capillary and mixed using a negative voltage. Mixing voltage, its duration, the concentration of acetic acid in the reaction zone, and the waiting time between mixing and separation were optimized. To show the applicability of the procedure to a broader range of analytes, a mixture of different types of saccharides, that is, xylose (pentose), fucose (hexose), glucose (hexose), N-acetylglucosamine (N-acetylaminosaccharide), and lactose (disaccharide), was subjected to derivatization and analysis under the optimal conditions. The linearity and repeatability of the process were evaluated as critical parameters for its analytical applications. Six-point calibration dependences in the 1-50 mM range showed excellent determination coefficients of 0.9992 or higher for all five saccharides tested. The repeatability of the labeled saccharide peak areas was between 2.2% and 4.3%., (© 2022 Wiley-VCH GmbH.)

Licensed glycoconjugate vaccines are generally prepared using native or sized polysaccharides coupled to a carrier protein through random linkages along the polysaccharide chain. These polysaccharides must be chemically modified before covalent linking to a carrier protein in order to obtain a more defined polysaccharide structure that leads to a more rational design and safer vaccines. There are classic and new methods for site-selective glycopolysaccharide conjugation, either chemical or enzymatic modification of the polysaccharide length or of specific amino acid residues of the protein carrier. Here, we discuss the state of the art and the advancement of conjugation of S. pneumoniae glycoconjugate vaccines based on pneumococcal capsular polysaccharides to improve existing vaccines.

Amino acid biosynthesis initiates with the reductive amination of α-ketoglutarate with ammonia to produce glutamate. However, the other α-keto acids derived from the glyoxylate and Krebs cycles are converted into amino acids by transamination, rather than by reductive amination. Why is only one amino acid synthesized by reductive amination and not the others? To explore this question, we quantified the inherent reactivities of keto acids in nonenzymatic reduction and reductive amination by using BH 3 CN - as a model nucleophile. Biological α-keto acids were found to show pronounced nonenzymatic reactivity differences for the formation of amino acids (α-ketoglutarate

Herein, we show how the merge of biocatalysis with flow chemistry aided by 3D-printing technologies can facilitate organic synthesis. This concept was exemplified for the reductive amination of benzaldehyde catalysed by co-immobilised amine dehydrogenase and formate dehydrogenase in a continuous flow micro-reactor. For this purpose, we investigated enzyme co-immobilisation by covalent binding, or ion-affinity binding, or entrapment. Entrapment in an agarose hydrogel turned out to be the most promising solution for this biocatalytic reaction. Therefore, we developed a scalable and customisable approach whereby an agarose hydrogel containing the co-entrapped dehydrogenases was cast in a 3D-printed mould. The reactor was applied to the reductive amination of benzaldehyde in continuous flow over 120 h and afforded 47 % analytical yield and a space-time yield of 7.4 g L day -1 using 0.03 mol% biocatalysts loading. This work also exemplifies how rapid prototyping of enzymatic reactions in flow can be achieved through 3D-printing technology., (© 2022 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

A pyridoneimine-catalyzed oxa-Michael addition of protecting groups-free, native mono- and disaccharides with Michael acceptors in aq. solution is reported. Several mono- and disaccharides are reacted with acceptors, namely, methylvinyl ketone, acrylonitrile and tert-butyl acrylate in aq. solution, the addition catalyzed by n-pentylpyridone imine. The addition occurs site-selectively at the anomeric lactol and the remaining hydroxy functionalities are un-affected. The resulting keto-glycopyranoside products are explored in aldol, allylation and oxime product formation, occurring at either α-methyl moiety or at the keto-moiety, with appropriate synthons. In another direction, the keto-glycopyranoside is functionalized further with amino acids through reductive amination in aq. methanol solution. Formation of hemiacetal anion occurs in the presence of pyridoneimine in aq. Solution, enabling subsequent addition to occur with acceptors. Facile reductive amination of the resulting keto-glycoside provides an avenue for conjugations with amino acids in the present work., (Copyright © 2022 Elsevier Ltd. All rights reserved.)