5597-50-2Relevant articles and documents
Reduction of Electron-Deficient Alkenes Enabled by a Photoinduced Hydrogen Atom Transfer
Larionova, Natalia A.,Ondozabal, Jun Miyatake,Cambeiro, Xacobe C.
supporting information, p. 558 - 564 (2020/12/07)
Direct hydrogen atom transfer from a photoredox-generated Hantzsch ester radical cation to electron-deficient alkenes has enabled the development of an efficient formal hydrogenation under mild, operationally simple conditions. The HAT-driven mechanism is supported by experimental and computational studies. The reaction is applied to a variety of cinnamate derivatives and related structures, irrespective of the presence of electron-donating or electron-withdrawing substituents in the aromatic ring and with good functional group compatibility. (Figure presented.).
Semi-aromatic biobased polyesters derived from lignin and cyclic carbonates
Horn, Jessica,Locklin, Jason,Ring, John,White, Evan M.,Winfield, Demichael
supporting information, p. 9658 - 9668 (2021/12/09)
The synthesis of biobased aromatic polyesters from lignin-derived monomers has become well described in the literature, but robust extrusion, thermomechanical, tensile and degradation studies of these materials is lacking. In this work, we have systematically investigated the mechanical and biodegradation properties of semi-aromatic polyesters that can potentially be derived from lignin. AB monomers were synthesized from reduced analogues of coumaric, ferulic, and sinapic acids along with cyclic carbonates, where the synthetic methodology was assessed using E-Factor and EcoScale. Polymerization yielded both semi-crystalline and amorphous polyesters with mechanical properties varying over three orders of magnitude. Detailed characterization revealed a wide array of properties including a highly ductile thermoplastic, a strong and rigid thermoplastic, and an elastomer. Composting biodegradation tests showed both degradable and nondegradable polymers can be achieved in this class. This work demonstrates the versatility of this class of polymers and illustrates their potential to replace non-sustainably derived plastics. This journal is
Preparation method of iprolol hydrochloride
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Paragraph 0053-0055; 0074, (2021/10/11)
The invention provides a preparation method of iprolol hydrochloride. The method comprises the following steps: reacting thionyl chloride and methanol to prepare methyl chloride. Methyl p-hydroxyphenylpropionic acid methyl ester is prepared by substitution reaction of p-hydroxyphenylpropionic acid and methyl chlorite. The etherification reaction of methyl hydroxy phenylpropionic acid methyl ester and epichlorohydrin is prepared to obtain 3 - [4 - (2, 3 - epoxypropoxy] phenylpropionic acid methyl ester. 3 - [4 - (2, 3 - Epoxypropoxy] phenylpropionic acid methyl ester and isopropylamine undergo amination reaction to prepare the ilomolol. Diaprolol hydrochloride and hydrochlorination of hydrogen chloride to obtain ilomolol hydrochlorideThe method has the advantages of easily available raw materials, low cost and simple preparation method. The target product has high yield, high purity and market competitiveness.
A 2-formylphenylboronic acid (2FPBA)-maleimide crosslinker: a versatile platform for Cys-peptide-hydrazine conjugation and interplay
António, Jo?o P. M.,Faustino, Hélio,Gois, Pedro M. P.
, p. 6221 - 6226 (2021/07/28)
In this work, we describe the preparation of a heterobifunctional 2-formylphenylboronic acid (2-FPBA)-maleimide crosslinker and explore its versatility in the preparation of various bioconjugates. We demonstrate the straightforward attachment of hydrazine payloads to cysteine residues in peptides, as well as the crosslinking of different thiol-bearing peptides or payloads withN-terminal cysteine peptides. Importantly, the dynamic nature of the 2-FPBA handle enables an interplay between the thiazolidine and diazaborine forms, which allows obtaining various products controlled by (and in some cases independent of) the order of addition of the components.
Diazaborines Are a Versatile Platform to Develop ROS-Responsive Antibody Drug Conjugates**
Aguiar, Sandra I.,André, Ana S.,António, Jo?o P. M.,Bernardes, Gon?alo J. L.,Carvalho, Joana Inês,Dias, Joana N. R.,Faustino, Hélio,Gois, Pedro M. P.,Lopes, Ricardo M. R. M.,Veiros, Luis F.,da Silva, Frederico A.
supporting information, p. 25914 - 25921 (2021/11/09)
Antibody–drug conjugates (ADCs) are a new class of therapeutics that combine the lethality of potent cytotoxic drugs with the targeting ability of antibodies to selectively deliver drugs to cancer cells. In this study we show for the first time the synthesis of a reactive-oxygen-species (ROS)-responsive ADC (VL-DAB31-SN-38) that is highly selective and cytotoxic to B-cell lymphoma (CLBL-1 cell line, IC50 value of 54.1 nM). The synthesis of this ADC was possible due to the discovery that diazaborines (DABs) are a very effective ROS-responsive unit that are also very stable in buffer and in plasma. DFT calculations performed on this system revealed a favorable energetic profile (ΔGR=?74.3 kcal mol?1) similar to the oxidation mechanism of aromatic boronic acids. DABs’ very fast formation rate and modularity enabled the construction of different ROS-responsive linkers featuring self-immolative modules, bioorthogonal functions, and bioconjugation handles. These structures were used in the site-selective functionalization of a VL antibody domain and in the construction of the homogeneous ADC.
Preparation process of high-purity iprolol hydrochloride
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Paragraph 0031, (2021/11/19)
The invention belongs to the technical field of organic chemistry and medical chemistry. In particular, the invention relates to a preparation process of high-purity iprolol hydrochloride. To the preparation process, p-hydroxyphenylpropionic acid and methanol are subjected to esterification reaction under the action of first catalyst, and the p-hydroxyphenylpropionic acid methyl ester and epoxy chloropropane are reacted under the action of second catalyst to obtain 3 - [4 - (2, 3 - epoxypropoxy) phenyl] propanoate, and then, methyl propionate is added in the methyl alcohol solvent in this order to obtain methyl p-hydroxybenzenepropanoic acid methyl ester and then in a methanolic solvent, and then the 3 - preparation 4 - process 2 can 3 - be carried out. The crude hydrochloride and hydrogen chloride is subjected to heating dissolution, activated carbon decoloration, cooling crystallization and centrifugation and drying operation in sequence to obtain final high-purity ilomolol hydrochloride with a total impurity lower than 0.5% and a single unknown single impurity lower than 0.05%.
Synthesis of HBED–CC–tris(tert-butyl ester) using a solid phase and a microwave reactor
Jerzyk,Kludkiewicz,Pijarowska-Kruszyna,Jaron,Maurin,Sikora,Kordowski,Garnuszek
, (2021/03/15)
N,N′-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N′-diacetic acid (HBED-CC) belongs to the acyclic, bifunctional complexing compounds used mainly for radiolabeling with gallium-68 (68Ga). Due to the high stability of the 68Ga3+complex, HBED-CC is well known for its rapid and efficient labeling at ambient temperature and the high stability of the complexes in vivo. The HBED-CC chelator in combination with a PSMA (Prostate Specific Membrane Antigen) inhibitor and labeled with isotope of gallium is an important tool for diagnosing the stage of cancer in patients with prostate cancer. Many HBED-CC derivatives have been described in the literature, but one of the most commonly used is 3-(3-{[(2-{[5-(2-tert-butoxycarbonylethyl)-2-hydroxybenzyl]-tert-butoxycarbonylmethylamino}-ethyl)-tert-butoxy-carbonylmethylamino]-methyl}-4-hydroxyphenyl)propionic acid (HBED–CC–tris(tert-butyl ester)). This compound is very expensive and commercially limited. Therefore this work describes an innovative method of synthesis on solid phase using of a microwave reactor. Optimization of the reaction allowed to obtain HBED-CC-tris(tert-butyl ester) with high purity and yield.
A General Organocatalytic System for Electron Donor-Acceptor Complex Photoactivation and Its Use in Radical Processes
De Pedro Beato, Eduardo,Melchiorre, Paolo,Spinnato, Davide,Zhou, Wei
supporting information, p. 12304 - 12314 (2021/08/20)
We report herein a modular class of organic catalysts that, acting as donors, can readily form photoactive electron donor-acceptor (EDA) complexes with a variety of radical precursors. Excitation with visible light generates open-shell intermediates under mild conditions, including nonstabilized carbon radicals and nitrogen-centered radicals. The modular nature of the commercially available xanthogenate and dithiocarbamate anion organocatalysts offers a versatile EDA complex catalytic platform for developing mechanistically distinct radical reactions, encompassing redox-neutral and net-reductive processes. Mechanistic investigations, by means of quantum yield determination, established that a closed catalytic cycle is operational for all of the developed radical processes, highlighting the ability of the organic catalysts to turn over and iteratively drive every catalytic cycle. We also demonstrate how the catalysts' stability and the method's high functional group tolerance could be advantageous for the direct radical functionalization of abundant functional groups, including aliphatic carboxylic acids and amines, and for applications in the late-stage elaboration of biorelevant compounds and enantioselective radical catalysis.
Engineering Boron Hot Spots for the Site-Selective Installation of Iminoboronates on Peptide Chains
Russo, Roberto,Padanha, Rita,Fernandes, Fábio,Veiros, Luis F.,Corzana, Francisco,Gois, Pedro M. P.
supporting information, p. 15226 - 15231 (2020/10/20)
Boronic acids (BAs) are a promising bioconjugation function to design dynamic materials as they can establish reversible covalent bonds with oxygen/nitrogen nucleophiles that respond to different pH, ROS, carbohydrates and glutathione levels. However, the dynamic nature of these bonds also limits the control over the stability and site-selectivity of the bioconjugation, which ultimately leads to heterogeneous conjugates with poor stability under physiological conditions. Here we disclose a new strategy to install BAs on peptide chains. In this study, a “boron hot spot“ based on the 3-hydroxyquinolin-2(1H)-one scaffold was developed and upon installation on a peptide N-terminal cysteine, enables the site-selective formation of iminoboronates with 2-formyl-phenyl boronic acids (Ka of 58128±2 m?1). The reaction is selective in the presence of competing lysine ?-amino groups, and the resulting iminoboronates, displayed improved stability in buffers solutions and a cleavable profile in the presence of glutathione. Once developed, the methodology was used to prepare cleavable fluorescent conjugates with a laminin fragment, which enabled the validation of the 67LR receptor as a target to deliver cargo to cancer HT29 cells.
Exploring bulky natural and natural-like periphery in the design of p-(benzyloxy)phenylpropionic acid agonists of free fatty acid receptor 1 (GPR40)
Gureev, Maxim,Krasavin, Mikhail,Kuranov, Sergey O.,Luzina, Olga A.,Onopchenko, Oleksandra,Pishel, Iryna,Salakhutdinov, Nariman F.,Zozulya, Sergey
, (2020/04/15)
Six derivatives of 3-phenylpropionic acid bearing various natural and natural-like, spatially defined peripheral motifs have been synthesized and evaluated in vitro for free fatty acid receptor 1 (FFA1) activation. Two frontrunner compounds (bearing a bornyl and cytosine groups) were evaluated in an oral glucose tolerance test in mice where both demonstrated the ability to sustain blood glucose levels following a glucose challenge. The bornyl compound displayed a somewhat superior, dose-dependent efficacy and, therefore, can be regarded as a lead compounds for further development as a therapeutic agent for type 2 diabetes mellitus. Its high affinity to FFA1 was rationalized by docking experiments.
