Stereoselective synthesis of spirocyclic compounds containing heterocyclic motifs represents a formidable challenge in enantioselective synthesis. Here, we present a cascade reaction between α,β-unsaturated aldehydes and isoxazolones under synergistic catalysis of a chiral secondary amine and a palladium(0) catalyst. This strategy allows access to chiral spiroisoxazolone derivatives with a large substrate scope tolerance and high levels of diastereoselectivity (dr up to 20:1) and enantioselectivity (up to 99% ee). Furthermore, the utility of this methodology is showcased by the transformation of chiral spiroisoxazolones into structurally attractive and enantiomerically enriched cyclopentene carboxylic acids with two stereogenic centers.
- Publication type
- Journal Article MeSH
Herein, we demonstrate an efficient method for multi-deuterium labelling of pirtobrutinib-a Bruton's tyrosine kinase inhibitor recently approved by the FDA-using a straightforward hydrogen isotope exchange (HIE) reaction. A remarkably high level of deuterium incorporation was achieved using an excess of a Kerr-type iridium catalyst. The key factor in the significant deuterium labelling was the decision to employ a deuterium uniformly labelled solvent, chlorobenzene-d5, at an elevated temperature. Virtually, no d0-d3 species were detected, with only traces of d4-d5 isotopomers (< 5%) observable in the mass spectrum of pirtobrutinib-d8, fulfilling requirements for stable isotope-labelled internal standard. The labelled compound-mainly consisting of isotopomers d6-d9 at 82.4% of the total abundance-was isolated in a high yield (73%) and purity (99%). Noteworthy, fluorine group acting as a directing group was observed for the first time. Significant incorporation of deuterium in ortho-positions, exceeding 87%, was observed. Interestingly, chlorinated solvent used in the HIE reactions was non-specifically deuterated yielding up to 0.42 deuterium per chlorobenzene molecule even at an exceptionally low iridium catalyst loading of 4.17 × 10-2 mol%.
- MeSH
- Deuterium * chemistry MeSH
- Isotope Labeling * MeSH
- Piperidines chemistry MeSH
- Pyrimidines chemistry MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Despite advancements in transplant immunology and vascularized composite allotransplantation (VCA), the longevity of allografts remains hindered by the challenge of allograft rejection. The acute-phase response, an immune-inflammatory reaction to ischemia/reperfusion that occurs directly after allogeneic transplantation, serves as a catalyst for graft rejection. This immune response is orchestrated by acute-phase reactants through intricate crosstalk with the mononuclear phagocyte system. OBJECTIVE: C-reactive protein (CRP), a well-known marker of inflammation, possesses pro-inflammatory properties and exacerbates ischemia/reperfusion injury. Thus, we investigated how CRP impacts acute allograft rejection. METHODS: Prompted by clinical observations in facial VCAs, we employed a complex hindlimb transplantation model in rats to investigate the direct impact of CRP on transplant rejection. RESULTS: Our findings demonstrate that CRP expedites allograft rejection and diminishes allograft survival by selectively activating non-classical monocytes. Therapeutic stabilization of CRP abrogates this activating effect on monocytes, thereby attenuating acute allograft rejection. Intravital imagining of graft-infiltrating, recipient-derived monocytes during the early phase of acute rejection corroborated their differential regulation by CRP and their pivotal role in driving the initial stages of graft rejection. CONCLUSION: The differential activation of recipient-derived monocytes by CRP exacerbates the innate immune response and accelerates clinical allograft rejection. Thus, therapeutic targeting of CRP represents a novel and promising strategy for preventing acute allograft rejection and potentially mitigating chronic allograft rejection.
- Publication type
- Journal Article MeSH
The piperidine-based Takemoto catalyst has been successfully employed in a novel asymmetric transfer hydroxymethylation of activated isoindolinones, allowing us to prepare the enantioenriched hydroxymethylated adducts in good to excellent yields (48-96%) and enantiopurities (81:19-97:3 e.r.). To increase the reaction rate without compromising the selectivity, carefully optimized formaldehyde surrogates were employed, providing a convenient source of anhydrous formaldehyde with a base-triggered release. The substrate scope, including 34 entries, showed the considerable generality of the asymmetric transformation, and most entries exhibited complete conversions in 24-48 h. A scale-up experiment and multiple enantioselective downstream transformations were also carried out, suggesting the prospective synthetic utility of the products.
- Publication type
- Journal Article MeSH
Deficit či obtížné dosahování ženského orgazmu je považováno v klasifikačních systémech pohlavních dysfunkcí za poruchu komplikující párovousexualitu. Tato premisa je běžně přijímána, přestože je koitální anorgazmie většinovou statistickou normou a dosažení orgazmu zevní stimulací není u žen tak snadné jako u mužů. Projevy ženského vyvrcholení jsou variabilní a souvisí s mnoha proměnlivými faktory. Některé teorie předpokládají vysokou míru korelace mezi schopností orgastického prožitku, sexuálními postoji a chováním, ale také souvislosti s reprodukčním potenciálem či stabilitou partnerských vztahů. Ženský orgazmus je mnohdy vnímán jako diskriminační mechanizmus determinující postoje k sexualitě nebo je dokonce považován za jakýsi katalyzátor plodnosti. Konsenzus o jeho významu neexistuje. Relevantní studie vyvracejí teorie o jeho pozitivních partnerských adaptačních funkcích i o vlivu na fertilitu. Orgazmus je u žen, pravděpodobně, vedlejším evolučním produktem jeho mužské varianty, neboť klitoris i penis mají identický embryonální základ. Ženská anorgazmie by neměla být považována za jednoznačnou diagnózu, natož za paradigma psychiatrického konstruktu působící frustrace či jiné problémy.
A deficit or problematic achievement of female orgasm is often classified as a sexual disorder that creates complications in the sex life of couples. This assumption is generally accepted, even though vaginal anorgasmia is an accepted statistical norm and non-coital methods of generating female orgasm are not as easy as they are for men. Female orgasms manifest themselves in different ways; they are variable and can be dependent on a number of variable factors. Some theories suggest a high degree of correlation between the capacity for orgasmic experience, sexual attitudes and behaviour, but also with reproductive potential or the stability of the given couple’s relationship. Female orgasm is often seen as a discriminatory mechanism influencing attitudes towards sexuality or even as a kind of fertility catalyst. There is no consensus on the importance of female orgasm. The results of some relevant studies refute theories about the female orgasm’s positive influence on adaptive functions of the couple’s relationship, as well as its influence on fertility. The orgasm in women is most likely an evolutionary by-product of its male variant, since the clitoris and penis have an identical embryonic basis of development. Female anorgasmia should not be considered an unquestioned diagnosis, let alone a psychiatric construct leading to a paradigm in which anorgasmia is categorically the cause of frustration or other problems.
- MeSH
- Clitoris physiology MeSH
- Humans MeSH
- Orgasm * MeSH
- Reproduction physiology MeSH
- Sexual Behavior * physiology MeSH
- Sexual Dysfunction, Physiological etiology MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Review MeSH
Anionic cyclopentadienyl (Cp) and its pentamethyl-substituted derivative (Cp*) serve as crucial ligands for creating stable π-coordinated materials, including catalysts. From a structural perspective, the π-extended analog of Cp, known as an N-fused porphyrin (NFP), is recognized as an intriguing 18π aromatic chromophore, offering near-infrared (NIR) optical properties that can be fine-tuned through metal complexation. When coordinated with rhodium at the central NFP core, it forms a sandwich binuclear rhodium(III) complex along with terminal and bridging chloride ligands, denoted as Rh-1, and its bromo derivative, Rh-1-Br. In contrast to the bis-NFP complex of iron(II) reported previously by our team, both Rh-1 and Rh-1-Br complexes exhibit strong NIR optical properties and narrow HOMO-LUMO energy gaps, attributed to minimal orbital interactions between the two co-facial NFP ligands. Leveraging these NIR absorption properties, we assessed the photothermal conversion properties of Rh-1 and ligand 1, revealing high conversion efficiency. This suggests their potential application as photothermal agents for use in photothermal therapy.
... proteins 33 -- 3.2.1 Proteins as structural components of cells and tissues 33 -- 3.2.2 Proteins as catalysts ...
1st edition 268 stran : ilustrace ; 30 cm
- Conspectus
- Biochemie. Molekulární biologie. Biofyzika
- Učební osnovy. Vyučovací předměty. Učebnice
- NML Fields
- biologie
- NML Publication type
- učebnice vysokých škol
Lignins are the most abundant biopolymers that consist of aromatic units. Lignins are obtained by fractionation of lignocellulose in the form of "technical lignins". The depolymerization (conversion) of lignin and the treatment of depolymerized lignin are challenging processes due to the complexity and resistance of lignins. Progress toward mild work-up of lignins has been discussed in numerous reviews. The next step in the valorization of lignin is the conversion of lignin-based monomers, which are limited in number, into a wider range of bulk and fine chemicals. These reactions may need chemicals, catalysts, solvents, or energy from fossil resources. This is counterintuitive to green, sustainable chemistry. Therefore, in this review, we focus on biocatalyzed reactions of lignin monomers, e.g., vanillin, vanillic acid, syringaldehyde, guaiacols, (iso)eugenol, ferulic acid, p-coumaric acid, and alkylphenols. For each monomer, its production from lignin or lignocellulose is summarized, and, mainly, its biotransformations that provide useful chemicals are discussed. The technological maturity of these processes is characterized based on, e.g., scale, volumetric productivities, or isolated yields. The biocatalyzed reactions are compared with their chemically catalyzed counterparts if the latter are available.
Nitroalkane oxidases (NAOs) are flavoenzymes that catalyse the oxidation of nitroalkanes to their corresponding carbonyl compounds while producing nitrite anions. Herein, we present an artificial catalytic system using flavins or ethylene-bridged flavinium salts that works via an NAO-like process. Under conditions optimised in terms of solvent, base, temperature and oxygen pressure, primary nitroalkanes were transformed to aldehydes. In our system, aldehydes immediately reacted with other nitroalkane molecules to form β-nitroalcohols. The reduced flavin catalyst was re-oxidised by oxygen. An alternative mechanism towards β-nitroalcohols via 5-(2-nitrobutyl)-1,5-dihydroflavin was suggested through quantum chemical calculations and by trapping and characterising this dihydroflavin intermediate. Interestingly, 5-(2-nitrobutyl)-1,5-dihydroflavin is an analogue of the flavin adenine dinucleotide adduct previously observed in an NAO X-ray structure. In both mechanistic pathways, flavin-5-iminium species is formed by nitroalkanide addition to flavin. This process represents flavin-based umpolung of an original donor to an acceptor.
- Publication type
- Journal Article MeSH
Structured catalytic membranes with high porosity and a low pressure drop are particularly suitable for industrial processes carried out at high space velocities. One of these processes is the catalytic total oxidation of volatile organic compounds, which is an economically feasible and environmentally friendly way of emission abatement. Noble metal catalysts are typically preferred due to high activity and stability. In this paper, the preparation of a thermally stable polybenzimidazole electrospun membrane, which can be used as a support for a platinum catalyst applicable in the total oxidation of volatile organic compounds, is reported for the first time. In contrast to commercial pelletized catalysts, high porosity of the membrane allowed for easy accessibility of the platinum active sites to the reactants and the catalytic bed exhibited a low pressure drop. We have shown that the preparation conditions can be tuned in order to obtain catalysts with a desired platinum particle size. In the gas-phase oxidation of ethanol, acetone, and toluene, the catalysts with Pt particle sizes 2.1 nm and 26 nm exhibited a lower catalytic activity than that with a Pt particle size of 12 nm. Catalysts with a Pt particle size of 2.1 nm and 12 nm were prepared by equilibrium adsorption, and the higher catalytic activity of the latter catalyst was ascribed to more reactive adsorbed oxygen species on larger Pt nanoparticles. On the other hand, the catalyst with a Pt particle size of 26 nm was prepared by a solvent evaporation method and contained less active polycrystalline platinum. Last but not least, the catalyst containing only 0.08 wt.% of platinum achieved high conversion (90%) of all the model volatile organic compounds at moderate temperatures (lower than 335 °C), which is important for reducing the costs of the abatement technology.
- Publication type
- Journal Article MeSH
