69605-90-9Relevant articles and documents
Experimental and density functional theory studies on hydroxymethylation of phenylboronic acids with paraformaldehyde over a Rh-PPh3 catalyst
Wang, Kuan,Lan, Jie,He, Zhen-Hong,Cao, Zhe,Wang, Weitao,Yang, Yang,Liu, Zhao-Tie
, (2020/12/01)
The synthesis of benzyl alcohols (BAs) is highly vital for their wide applications in organic synthesis and pharmaceuticals. Herein, BAs was efficiently synthesized via hydroxymethylation of phenylboronic acids (PBAs) and paraformaldehyde over a simple Rh-PPh3 catalyst combined with an inorganic base (NaOH). A variety of BAs with the groups of CH3?, CH3O?, Cl?, Br?, and so on were obtained with moderate to good yields, indicating that the protocol had a good universality. Density functional theory (DFT) calculations proposed the Hayashi-type arylation mechanism involved the arylation step of PBA and Rh(OH)(PPh3)2 catalyst to form Rh(I)-bound aryl intermediates and the hydrolysis step of Rh(I)-bound aryl intermediates and HCHO to generate BA product (the rate-determining step). The present route provides a valuable and direct method for the synthesis of BAs and expands the application range of paraformaldehyde.
AMINOPEPTIDASE A INHIBITORS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
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Page/Page column 54-55, (2020/06/10)
The present invention relates to a novel compound, to a composition comprising the same, to methods for preparing the compound, and the use of this compound in therapy. In particular, the present invention relates to compound that is useful in the treatment and prevention of primary and secondary arterial hypertension, ictus, myocardial ischaemia, cardiac and renal insufficiency, myocardial infarction, peripheral vascular disease, diabetic proteinuria, Syndrome X and glaucoma.
Pd-catalyzed atom-efficient cross-coupling of triarylbismuth reagents with protecting group-free iodophenylmethanols: Synthesis of biarylmethanols
Meka, Suresh,Rao, Maddali L. N.
supporting information, (2020/02/11)
An atom-efficient procedure for the synthesis of functionalized biarylmethanols via the Pd-catalyzed cross-coupling reactions of differently functionalized iodophenylmethanols and triarylbismuth reagents is described. This protecting group-free direct couplings of 2-, 3- or 4-iodophenylmethanols with triarylbismuth reagents afforded biarylmethanols in good to high yields.
Compound, pharmaceutically acceptable salt thereof and medical application thereof
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Paragraph 0256-0261, (2020/07/24)
The invention belongs to the field of medicines, and particularly relates to a compound shown as a formula I or medicinal salt thereof. The invention also relates to application of the compound or themedicinal salt thereof in selectively inhibiting LF activity, resisting anthrax toxin toxicity and preventing or treating anthracnose.
Gold catalysis for selective hydrogenation of aldehydes and valorization of bio-based chemical building blocks
Silva, Rerison J. M.,Fiorio, Jhonatan L.,Vidinha, Pedro,Rossi, Liane M.
, p. 2162 - 2169 (2019/12/30)
Gold catalysts are best known for their selectivity in oxidation reactions, however, there is a promising future for gold in selective hydrogenations. Herein, the hydrogenation of several aldehydes and important bio-based chemical building blocks, namely 5-hydroxymethylfurfural (5-HMF), furfural and vanillin, was performed throughout the combination of Au nanoparticles with Lewis bases. The Au-amine ligand (e.g., 2,4,6-trimethylpyridine) catalytic system could reduce the aldehyde carbonyl group selectively, without reducing alkene moieties or opening the furanic ring that occur on most traditional catalysts. Otherwise, the reduction of nitro group is preferential and the catalytic system was used for the synthesis of furfurylamines, important intermediates in the synthesis of different pharmaceuticals (e.g., furosemide), through the selective reductive amination of furfural starting from nitro-compounds. Moreover, a fully heterogeneous gold catalyst embedded in N-doped carbon (Au@N-doped carbon / TiO2) was able to perform these reactions in successive recycles without the addition of ligands, with impact in the development of a continuous flow process for biomass valorization.
Pd–Ni bimetallic nanoparticles supported on ZrO2 as an efficient catalyst for Suzuki–Miyaura reactions
Zhang, Li-Jie,Yao, Xian,Sun, Ying-xin,Zhang, Jia-wei,Cai, Chun
, p. 419 - 423 (2018/09/12)
Pd–Ni bimetallic nanoparticles (BMNPs) supported on ZrO2 were prepared by an impregnation–reduction method. The BMNPs showed excellent catalytic performance in Suzuki carbon–carbon cross-coupling reactions and almost quantitative conversion of the substrates was obtained under mild conditions in the absence of ligand. The excellent catalytic performance of the bimetallic catalyst could be a result of the synergistic effect between the two metal components. The catalyst showed outstanding recyclability during the reaction process; no obvious decrease in catalytic performance was observed after five cycles.
URIDINE NUCLEOSIDE DERIVATIVES, COMPOSITIONS AND METHODS OF USE
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Paragraph 0191; 198; 0236, (2018/04/20)
This disclosure relates to uridine nucleoside derivatives, compositions comprising therapeutically effective amounts of those nucleoside derivatives and methods of using those nucleoside derivatives or compositions in treating disorders that are responsive to compounds, such as agonists, of P2Y6 receptor, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) and traumatic CNS injury, pain, Down Syndrome (DS), glaucoma and inflammatory conditions.
Probing the Hydrophobic Binding Pocket of G-Protein-Coupled Lysophosphatidylserine Receptor GPR34/LPS1 by Docking-Aided Structure-Activity Analysis
Sayama, Misa,Inoue, Asuka,Nakamura, Sho,Jung, Sejin,Ikubo, Masaya,Otani, Yuko,Uwamizu, Akiharu,Kishi, Takayuki,Makide, Kumiko,Aoki, Junken,Hirokawa, Takatsugu,Ohwada, Tomohiko
supporting information, p. 6384 - 6399 (2017/08/02)
The ligands of certain G-protein-coupled receptors (GPCRs) have been identified as endogenous lipids, such as lysophosphatidylserine (LysoPS). Here, we analyzed the molecular basis of the structure-activity relationship of ligands of GPR34, one of the LysoPS receptor subtypes, focusing on recognition of the long-chain fatty acid moiety by the hydrophobic pocket. By introducing benzene ring(s) into the fatty acid moiety of 2-deoxy-LysoPS, we explored the binding site's preference for the hydrophobic shape. A tribenzene-containing fatty acid surrogate with modifications of the terminal aromatic moiety showed potent agonistic activity toward GPR34. Computational docking of these derivatives with a homology modeling/molecular dynamics-based virtual binding site of GPR34 indicated that a kink in the benzene-based lipid surrogates matches the L-shaped hydrophobic pocket of GPR34. A tetrabenzene-based lipid analogue bearing a bulky tert-butyl group at the 4-position of the terminal benzene ring exhibited potent GPR34 agonistic activity, validating the present hydrophobic binding pocket model.
The Oxidation of Hydrophobic Aromatic Substrates by Using a Variant of the P450 Monooxygenase CYP101B1
Sarkar, Md. Raihan,Lee, Joel H. Z.,Bell, Stephen G.
, p. 2119 - 2128 (2017/10/12)
The cytochrome P450 monooxygenase CYP101B1, from a Novosphingobium bacterium is able to bind and oxidise aromatic substrates but at a lower activity and efficiency than norisoprenoids and monoterpenoid esters. Histidine 85 of CYP101B1 aligns with tyrosine 96 of CYP101A1, which, in the latter enzyme forms the only hydrophilic interaction with its substrate, camphor. The histidine residue of CYP101B1 was mutated to phenylalanine with the aim of improving the activity of the enzyme for hydrophobic substrates. The H85F mutant lowered the binding affinity and activity of the enzyme for β-ionone and altered the oxidation selectivity. This variant also showed enhanced affinity and activity towards alkylbenzenes, styrenes and methylnaphthalenes. For example the rate of product formation for acenaphthene oxidation was improved sixfold to 245 nmol per nmol CYP per min. Certain disubstituted naphthalenes and substrates, such as phenylcyclohexane and biphenyls, were oxidised with lower activity by the H85F variant. Variants at H85 (A and G) designed to introduce additional space into the active site so as to accommodate these larger substrates did not improve the oxidation activity. As the H85F mutant of CYP101B1 improved the oxidation of hydrophobic substrates, this residue is likely to be in the substrate binding pocket or the access channel of the enzyme. The side chain of the histidine might interact with the carbonyl groups of the favoured norisoprenoid substrates of CYP101B1.
The selective oxidation of substituted aromatic hydrocarbons and the observation of uncoupling via redox cycling during naphthalene oxidation by the CYP101B1 system
Hall, Emma A.,Sarkar, Md Raihan,Bell, Stephen G.
, p. 1537 - 1548 (2017/06/05)
The cytochrome P450 monooxygenase enzyme CYP101B1, from Novosphingobium aromaticivorans DSM12444, efficiently and selectively oxidised a range of naphthalene and biphenyl derivatives. Methyl substituted naphthalenes were better substrates than ethylnaphthalenes and naphthalene itself. The highest product formation activity for a singly substituted alkylnaphthalene was obtained with 2-methylnaphthalene. The oxidation of alkylnaphthalenes was regioselective for the benzylic methyl or methine C-H bonds. The products from 1- and 2-ethylnaphthalene oxidation were highly enantioselective with a single stereoisomer being generated in significant excess. The disubstituted substrate, 2,7-dimethylnaphthalene, had a higher product formation activity than either 1- and 2-methylnaphthalene. Methyl substituted biphenyls were also better substrates than biphenyl and had similar biocatalytic parameters to 1-methylnaphthalene. CYP101B1 catalysed oxidation of 2- and 3-methylbiphenyl was selective for attack at the methyl C-H bonds. The exception was the turnover of 4-methylbiphenyl which generated 4′-(4-methylphenyl)phenol as the major product (70%) with 4-biphenylmethanol making up the remainder. The drug molecule diclofenac was also regioselectively oxidised to 4′-hydroxydiclofenac by CYP101B1. The activity of the CYP101B1 system with naphthalene was more complex and the rate of NADH oxidation increased over time but very little product, 1-naphthol, was generated. Addition of samples of 1-naphthol and 2-naphthol and low concentrations of 1,4-naphthoquinone induced rapid NADH oxidation activity in the in vitro turnovers in both the presence and absence of the cytochrome P450 enzyme. Hydrogen peroxide was generated in these reactions in absence of the P450 enzymes demonstrating that the ferredoxin and ferredoxin reductase in combination with quinones from naphthol oxidation and oxygen can undergo redox cycling giving rise to a form of uncoupling of the reducing equivalents.
