Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

The first synthesis of 2-amino-3,4-dihydroxycyclooctane-1-carboxylic acid, methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10-yl)carbamate, and 10-amino-6-hydroxy-8-oxabicyclo[5.2.1]decan-9-one starting from cis-9-azabicyclo[6.2.0]dec-6-en-10-one is described. cis-9-Azabicyclo[6.2.0]dec-6-en-10-one was transformed into the corresponding amino ester and its protected amine. Oxidation of the double bond in the N-Boc-protected methyl 2-aminocyclooct-3-ene-1-carboxylate then delivered the targeted amino acid and its derivatives. Density-functional theory (DFT) computations were used to explain the reaction mechanism for the ring opening of the epoxide and the formation of five-membered lactones. The stereochemistry of the synthesized compounds was determined by 1D and 2D NMR spectroscopy. The configuration of methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10-yl)carbamate was confirmed by X-ray diffraction.

Visible Light-driven Metal-free C–H Functionalization: Access to New Bioactive Tetrahydroisoquinoline-Butenolide Hybrids via Domino Amine Oxidation/Vinylogous Mannich Reaction

An efficient metal-free visible light-driven two-step domino reaction towards new bioactive tetrahydroisoquinoline-butenolide hybrid compounds was developed for the first time. Combination of fluorescein as photosensitizer and thiourea as an additive was found to be the most effective way to promote an aerobic amine oxidation/vinylogous Mannich domino reaction sequence with yields up to 97% for a broad substrate scope. While fluorescein without thiourea additive gave product in 84% yield, it was even observed that thiourea in absence of fluorescein is also able to promote formation of product with good yield of 75%, which is explained by a potential role of thiourea as an electron-transfer mediator in light-induced amine oxidation. Both experimental and computational evidence supported the crucial role of singlet oxygen in the developed C–H functionalization reaction. In addition, in vitro studies of tetrahydroisoquinoline-butenolide hybrid compounds demonstrated their high antischistosomal and anti-cancer activities.

Green Oxidation of Amines by a Novel Cold-Adapted Monoamine Oxidase MAO P3 from Psychrophilic Fungi Pseudogymnoascus sp. P3

The use of monoamine oxidases (MAOs) in amine oxidation is a great example of how biocatalysis can be applied in the agricultural or pharmaceutical industry and manufacturing of fine chemicals to make a shift from traditional chemical synthesis towards more sustainable green chemistry. This article reports the screening of fourteen Antarctic fungi strains for MAO activity and the discovery of a novel psychrozyme MAOP3 isolated from the Pseudogymnoascus sp. P3. The activity of the native enzyme was 1350 ± 10.5 U/L towards a primary (n-butylamine) amine, and 1470 ± 10.6 U/L towards a secondary (6,6-dimethyl-3-azabicyclohexane) amine. MAO P3 has the potential for applications in biotransformations due to its wide substrate specificity (aliphatic and cyclic amines, pyrrolidine derivatives). The psychrozyme operates at an optimal temperature of 30 °C, retains 75% of activity at 20 °C, and is rather thermolabile, which is beneficial for a reduction in the overall costs of a bioprocess and offers a convenient way of heat inactivation. The reported biocatalyst is the first psychrophilic MAO; its unique biochemical properties, substrate specificity, and effectiveness predispose MAO P3 for use in environmentally friendly, low-emission biotransformations.

Novel Facet of an Old Dietary Molecule? Direct Influence of Caffeine on Glucose and Biogenic Amine Handling by Human Adipocytes

Caffeine is a plant alkaloid present in food and beverages consumed worldwide. It has high lipid solubility with recognized actions in the central nervous system and in peripheral tissues, notably the adipose depots. However, the literature is scant regarding caffeine’s influence on adipocyte functions other than lipolysis, such as glucose incorporation into lipids (lipogenesis) and amine oxidation. The objective of this study was to explore the direct effects of caffeine and of isobutylmethylxanthine (IBMX) on these adipocyte functions. Glucose transport into fat cells freshly isolated from mice, rats, or humans was monitored by determining [3H]-2-deoxyglucose (2-DG) uptake, while the incorporation of radiolabeled glucose into cell lipids was used as an index of lipogenic activity. Oxidation of benzylamine by primary amine oxidase (PrAO) was inhibited by increasing doses of caffeine in human adipose tissue preparations with an inhibition constant (Ki) in the millimolar range. Caffeine inhibited basal and insulin-stimulated glucose transport as well as lipogenesis in rodent adipose cells. The antilipogenic action of caffeine was also observed in adipocytes from mice genetically invalidated for PrAO activity, indicating that PrAO activity was not required for lipogenesis inhibition. These caffeine inhibitory properties were extended to human adipocytes: relative to basal 2-DG uptake, set at 1.0 ± 0.2 for 6 individuals, 0.1 mM caffeine tended to reduce uptake to 0.83 ± 0.08. Insulin increased uptake by 3.86 ± 1.11 fold when tested alone at 100 nM, and by 3.21 ± 0.80 when combined with caffeine. Our results reinforce the recommendation of caffeine’s potential in the treatment or prevention of obesity complications.

Ozone-Mediated Amine Oxidation and Beyond: A Solvent Free, Flow-Chemistry Approach

Ozone is a powerful oxidant, most commonly used for oxidation of alkenes to carbonyls. The synthetic utility of other ozone-mediated reactions is hindered by its high reactivity and propensity to over-oxidize organic molecules, including most solvents. This challenge can largely be mitigated by adsorbing both substrate and ozone onto silica gel, providing a solvent-free oxidation method. In this manuscript, a flow-based packed bed reactor approach is described that provides exceptional control of reaction temperature and time of this reaction to achieve improved control and chemoselectivity over this challenging reaction. A powerful method to oxidize primary amines into nitroalkanes is achieved. Examples of pyridine, C–H bond, and arene oxidations are also demonstrated, confirming the system is generalizable to diverse ozone-mediated processes.<br>

Ozone-Mediated Amine Oxidation and Beyond: A Solvent Free, Flow-Chemistry Approach

Ozone is a powerful oxidant, most commonly used for oxidation of alkenes to carbonyls. The synthetic utility of other ozone-mediated reactions is hindered by its high reactivity and propensity to over-oxidize organic molecules, including most solvents. This challenge can largely be mitigated by adsorbing both substrate and ozone onto silica gel, providing a solvent-free oxidation method. In this manuscript, a flow-based packed bed reactor approach is described that provides exceptional control of reaction temperature and time of this reaction to achieve improved control and chemoselectivity over this challenging reaction. A powerful method to oxidize primary amines into nitroalkanes is achieved. Examples of pyridine, C–H bond, and arene oxidations are also demonstrated, confirming the system is generalizable to diverse ozone-mediated processes.<br>

Synthesis of Chiral Amines by C–C Bond Formation with Photoredox Catalysis

Chiral amines are key substructures of biologically active natural products and drug candidates. The advent of photoredox catalysis has changed the way synthetic chemists think about building these substructures, opening new pathways that were previously unavailable. New developments in this area are reviewed, with an emphasis on C–C bond constructions involving radical intermediates generated through photoredox processes.1 Introduction2 Radical–Radical Coupling of α-Amino Radicals2.1 Radical–Radical Coupling Involving Amine Oxidation2.2 Radical–Radical Coupling Involving Imine Reduction2.3 Couplings Involving both Amine Oxidation and Imine Reduction3 Addition Reactions of α-Amino Radicals3.1 Conjugate Additions of α-Amino Radicals3.2 Addition of α-Amino Radicals to Heteroaromatic Systems3.3 Cross Coupling via Additions to Transition Metal Complexes4 Radical Addition to C=N Bonds Using Photoredox Catalysis4.1 Intramolecular Radical Addition to C=N Bonds4.2 Intermolecular Radical Addition to C=N Bonds5 Conclusion

Aerobic primary and secondary amine oxidation cascade by a copper amine oxidase inspired catalyst

A CAO inspired catalyst catalyzed the cascade aerobic oxidation of primary and secondary amines for the synthesis of quinazolin-4(3H)-one core in high yields. Like the natural CAOs, a copper ion improves the o-quinone cofactor's catalytic activity.