4609-10-3Relevant articles and documents
Method for synthesizing 4-(4-fluorobenzoyl) butyric acid and analogues thereof in continuous flow microreactor
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Paragraph 0071-0076, (2021/05/12)
The invention relates to a method for synthesizing 4-(4-fluorobenzoyl) butyric acid and analogues thereof in a continuous flow microreactor, which comprises the following steps: (1) uniformly mixing a compound 1 and a compound 2 to obtain a homogeneous phase solution A; (2) uniformly mixing aluminum trichloride, a compound 1 and an organic solvent to obtain a homogeneous phase solution B; (3) diluting concentrated hydrochloric acid with water to prepare a solution C; and (4) transferring the homogeneous phase solution A and the homogeneous phase solution B into a first micro-reaction module for a Friedel-Crafts acylation reaction, after the reaction is finished, transferring the obtained reaction solution and the solution C into a second micro-reaction module for quenching reaction, and then performing liquid separation, washing and vacuum concentration to obtain a target compound 3; wherein the specific synthesis route is as follows. By adopting the method disclosed by the invention, the target product can be continuously and rapidly synthesized, aluminum trichloride is not needed for treatment, the reaction condition is mild, the reaction time is short, and the yield is high and reaches 90% or above.
Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride
Lansbergen, Beatrice,Meister, Catherine S.,McLeod, Michael C.
, p. 404 - 409 (2021/03/20)
A novel reactivity of 1,1,1-trifluoroalkanones is reported, where the reaction with AlCl3 results in the formation of 1,1-dichloro-1-alkenones. The reaction scope was found to be broad, with various chain lengths and aryl substituents tolerated. For substrates containing an electron-rich aromatic ring, further reactions take place, resulting in bicyclic and/or rearrangement products.
Site- And enantiodifferentiating C(sp3)-H oxidation enables asymmetric access to structurally and stereochemically diverse saturated cyclic ethers
Liu, Lei,Sun, Shutao,Yang, Yiying,Zhang, Dongju,Zhao, Ran
supporting information, p. 19346 - 19353 (2020/12/01)
A manganese-catalyzed site- and enantiodifferentiating oxidation of C(sp3)-H bonds in saturated cyclic ethers has been described. The mild and practical method is applicable to a range of tetrahydrofurans, tetrahydropyrans, and medium-sized cyclic ethers with multiple stereocenters and diverse substituent patterns in high efficiency with extremely efficient site- and enantiodiscrimination. Late-stage application in complex biological active molecules was further demonstrated. Mechanistic studies by combined experiments and computations elucidated the reaction mechanism and origins of stereoselectivity. The ability to employ ether substrates as the limiting reagent, together with a broad substrate scope, and a high level of chiral recognition, represent a valuable demonstration of the utility of asymmetric C(sp3)-H oxidation in complex molecule synthesis.
Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters
Shi, Yongjie,Tan, Xuefeng,Gao, Shuang,Zhang, Yao,Wang, Jingxin,Zhang, Xumu,Yin, Qin
supporting information, p. 2707 - 2713 (2020/03/30)
Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.
Aryl Boronic Acid Catalysed Dehydrative Substitution of Benzylic Alcohols for C?O Bond Formation
Estopi?á-Durán, Susana,Donnelly, Liam J.,Mclean, Euan B.,Hockin, Bryony M.,Slawin, Alexandra M. Z.,Taylor, James E.
supporting information, p. 3950 - 3956 (2019/02/16)
A combination of pentafluorophenylboronic acid and oxalic acid catalyses the dehydrative substitution of benzylic alcohols with a second alcohol to form new C?O bonds. This method has been applied to the intermolecular substitution of benzylic alcohols to form symmetrical ethers, intramolecular cyclisations of diols to form aryl-substituted tetrahydrofuran and tetrahydropyran derivatives, and intermolecular crossed-etherification reactions between two different alcohols. Mechanistic control experiments have identified a potential catalytic intermediate formed between the aryl boronic acid and oxalic acid.
Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations
Betori, Rick C.,May, Catherine M.,Scheidt, Karl A.
supporting information, p. 16490 - 16494 (2019/11/03)
Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.
Structure-Based Discovery of Thiosemicarbazone Metalloproteinase Inhibitors for Hemorrhage Treatment in Snakebites
Ferreira, Francis B.,Pereira, Thiago M.,Souza, Dayane L. N.,Lopes, Daiana S.,Freitas, Vitor,ávila, Veridiana M. R.,Kümmerle, Arthur E.,Sant'Anna, Carlos Mauricio R.
supporting information, p. 1136 - 1141 (2017/11/15)
The venoms of snakes are composed by many toxins, which are responsible for various toxic effects including intense pain, bleeding disorders, and local tissue damage caused by hemorrhage and necrosis. The snake venom metalloproteinases (SVMPs) are proteolytic zinc-dependent enzymes acting in different hemostatic mechanisms. In this work, a structure-based molecular modeling strategy was used for the rational design, by means of a homology 3D model of an SVMP isolated from Bothrops pauloensis venom (BpMP-I), followed by synthesis and in vitro evaluation of new thiosemicarbazones as the first inhibitors of the B. pauloensis SVMP. Besides being effective for the SVMP inhibition, two molecules were shown to be effective also in vivo, inhibiting hemorrhage caused by the B. pauloensis whole venom. Docking studies on metalloproteinases from other snake species suggest that the thiosemicarbazones activity is not confined to BpMP-I, but seems to be a common feature of metzincins.
Design and synthesis of 4,5,6,7‐tetrahydro‐1H‐1,2‐diazepin‐7‐one derivatives as a new series of Phosphodiesterase 4 (PDE4) inhibitors
Guariento, Sara,Karawajczyk, Anna,Bull, James A.,Marchini, Gessica,Bielska, Martyna,Iwanowa, Xenia,Bruno, Olga,Fossa, Paola,Giordanetto, Fabrizio
supporting information, p. 24 - 29 (2016/12/09)
Phosphodiesterase 4 (PDE4) inhibitors have attractive therapeutic potential in respiratory, inflammatory, metabolic and CNS disorders. The present work details the design, chemical exploration and biological profile of a novel PDE4 inhibitor chemotype. A
Visible-Light-Promoted Metal-Free Aerobic Oxidation of Primary Amines to Acids and Lactones
Cheng, Xiaokai,Yang, Bo,Hu, Xingen,Xu, Qing,Lu, Zhan
, p. 17566 - 17570 (2016/11/29)
A unique metal-free aerobic oxidation of primary amines via visible light photocatalytic double carbon–carbon bonds cleavage and multi carbon–hydrogen bonds oxidation was observed. Aerobic oxidation of primary amines could be controlled to afford acids by using dioxane with 18 W CFL, and lactones by using DMF with 8 W green LEDs, respectively. A plausible mechanism was proposed based on control experiments. This observation showed direct evidences for the fragmentation in the aerobic oxidation of aliphatic primary amines.
Ru-catalyzed asymmetric hydrogenation of δ-keto Weinreb amides: Enantioselective synthesis of (+)-Centrolobine
Zhao, Mengmeng,Lu, Bin,Ding, Guangni,Ren, Kai,Xie, Xiaomin,Zhang, Zhaoguo
, p. 2723 - 2730 (2016/03/05)
An efficient asymmetric hydrogenation of δ-keto Weinreb amides catalyzed by a Ru-Xyl-SunPhos-Daipen bifunctional catalyst has been achieved. This method afforded a series of enantio-enriched δ-hydroxy Weinreb amides in good yields (up to 93%) and enantioselectivities (up to 99%). This protocol was successfully applied to the synthesis of the key intermediate of (+)-Centrolobine.
