- Method for synthesizing 4-(4-fluorobenzoyl) butyric acid and analogues thereof in continuous flow microreactor
-
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.
- -
-
Paragraph 0071-0076
(2021/05/12)
-
- Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride
-
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.
- Lansbergen, Beatrice,Meister, Catherine S.,McLeod, Michael C.
-
p. 404 - 409
(2021/03/20)
-
- Site- And enantiodifferentiating C(sp3)-H oxidation enables asymmetric access to structurally and stereochemically diverse saturated cyclic ethers
-
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.
- Liu, Lei,Sun, Shutao,Yang, Yiying,Zhang, Dongju,Zhao, Ran
-
supporting information
p. 19346 - 19353
(2020/12/01)
-
- Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters
-
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.
- Shi, Yongjie,Tan, Xuefeng,Gao, Shuang,Zhang, Yao,Wang, Jingxin,Zhang, Xumu,Yin, Qin
-
supporting information
p. 2707 - 2713
(2020/03/30)
-
- Aryl Boronic Acid Catalysed Dehydrative Substitution of Benzylic Alcohols for C?O Bond Formation
-
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.
- 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)
-
- Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations
-
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.
- Betori, Rick C.,May, Catherine M.,Scheidt, Karl A.
-
supporting information
p. 16490 - 16494
(2019/11/03)
-
- Structure-Based Discovery of Thiosemicarbazone Metalloproteinase Inhibitors for Hemorrhage Treatment in Snakebites
-
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.
- 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)
-
- 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
-
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
- 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)
-
- Visible-Light-Promoted Metal-Free Aerobic Oxidation of Primary Amines to Acids and Lactones
-
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.
- Cheng, Xiaokai,Yang, Bo,Hu, Xingen,Xu, Qing,Lu, Zhan
-
p. 17566 - 17570
(2016/11/29)
-
- Ru-catalyzed asymmetric hydrogenation of δ-keto Weinreb amides: Enantioselective synthesis of (+)-Centrolobine
-
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.
- Zhao, Mengmeng,Lu, Bin,Ding, Guangni,Ren, Kai,Xie, Xiaomin,Zhang, Zhaoguo
-
p. 2723 - 2730
(2016/03/05)
-
- Racemic total synthesis of dactyloidin and demethyldactyloidin through the dl-proline-catalyzed Knoevenagel condensation/[4 + 2] cycloaddition cascade
-
An efficient approach towards the first racemic total synthesis of dactyloidin (2) and demethyldactyloidin (3) is described. Their oxygen-bridged tricyclic ketal systems were rapidly constructed by using a remarkable biomimetic Knoevenagel condensation/[4 + 2] cycloaddition cascade as the critical strategy and the 1,5-dicarbonyl segment was assembled by Grignard addition.
- Tan, Haibo,Liu, Hongxin,Chen, Xinzheng,Chen, Huiyu,Qiu, Shengxiang
-
supporting information
p. 9977 - 9983
(2015/10/12)
-
- Ultrasound-promoted Friedel-Crafts acylation of arenes and cyclic anhydrides catalyzed by ionic liquid of [bmim]Br/AlCl3
-
A simple and efficient method of Friedel-Crafts acylation of arenes with succinic anhydride, phthalic anhydride and glutaric anhydride under the action of 1-butyl-3-ethylimidazolium ([bmim]Br/AlCl3 ([bmim]+) cation (ionic liquid) and ultrasound irradiation is presented. Thy purity of products was tested by GC-MS and their structures evaluated by IR and 1H NMR spectroscopy.
- Fekri, Leila Zare,Nikpassand, Mohammad
-
p. 1825 - 1829
(2015/01/09)
-
- Synthesis of γ-, δ-, and ε-lactams by asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)iminoesters
-
Highly enantiomerically enriched γ- and δ-lactams have been prepared by a simple and very efficient procedure that involves the asymmetric transfer hydrogenation of N-(tert-butylsulfinyl)iminoesters followed by desulfinylation of the nitrogen atom and spo
- Guijarro, David,Pablo, Oscar,Yus, Miguel
-
p. 3647 - 3654
(2013/05/22)
-
- Catalytic asymmetric hydrogenation of δ-ketoesters: Highly efficient approach to chiral 1,5-diols
-
High turnover: An highly efficient catalytic asymmetric hydrogenation of δ-aryl-δ-ketoesters has been realized by using the chiral spiroiridium catalyst (R)-1. Chiral 1,5-diol products are obtained with excellent enantioselectivity and turnover numbers (TONs) as high as 100 000. TOF=turnover frequency. Copyright
- Yang, Xiao-Hui,Xie, Jian-Hua,Liu, Wei-Peng,Zhou, Qi-Lin
-
supporting information
p. 7833 - 7836
(2013/08/23)
-
- Synthesis and anti-inflammatory activity of some 3-(4,6-disubtituted-2- thioxo-1,2,3,4-tetrahydropyrimidin-5-yl) propanoic acid derivatives
-
A series of 3-(4,6-disubtituted-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl) propanoic acid derivatives has been synthesized by condensation of thiourea, 5-(4-subtituted phenyl)-5-oxopentanoic acid and substituted aldehyde. The synthesized compounds were screened for their anti-inflammatory activity using rat paw edema method. Most of the compounds from the series showed significant (p 0.05) anti-inflammatory activity.
- Mokale, Santosh N.,Shinde, Sandeep S.,Elgire, Rupali D.,Sangshetti, Jaiprakash N.,Shinde, Devanand B.
-
experimental part
p. 4424 - 4426
(2010/09/09)
-
- G-PROTEIN-CONJUGATED RECEPTOR AGONIST
-
Disclosed is a novel aralkyl carboxylic acid compound which has an agonistic activity on GPR-120 and/or GPR-40, particularly GPR-120, and is therefore useful as an appetite regulator, an anti-obesity agent, a therapeutic agent for diabetes, a pancreatic beta differentiating cell growth enhancer, a therapeutic agent for metabolic syndrome, a therapeutic agent for a gastrointestinal disease, a therapeutic agent for a neuropathy, a therapeutic agent for a mental disorder, a therapeutic agent for a pulmonary disease, a therapeutic agent for a pituitary hormone secretion disorder or a lipid flavoring/seasoning agent. The aralkyl carboxylic acid compound is represented by the general formula (I). (I) wherein the ring Q represents a pyridyl or the like; R1 represents a C1-6 alkyl group or the like; R2 represents a hydrogen atom, a C1-4 alkyl group or a C1-4 alkoxy group; m and n independently represent an integer of 1 to 5; and X represents an oxygen atom, a sulfur atom or - NR3- [wherein R3 represents a hydrogen atom or a C1-4 alkyl group].
- -
-
Page/Page column 33-34
(2010/03/02)
-
- Investigation into the structure-activity relationship of novel concentration dependent, dual action T-type calcium channel agonists/antagonists
-
This paper describes the synthesis and biological evaluation of a series of straight chain analogs of a compound (1) that was previously synthesized in our research program. These compounds, which are T-type calcium channel antagonists, exhibits potent anti-proliferative activity against a variety of cancer cells. A structure-activity relationship of these analogs against a variety of cancer cells has provided insight into a logical pharmacophore for this series of compounds. Furthermore, this series of compounds has presented itself as a set of novel, concentration dependent, dual action agonists/antagonists for the T-type calcium channel.
- McCalmont, William F.,Patterson, Jaclyn R.,Lindenmuth, Michael A.,Heady, Tiffany N.,Haverstick, Doris M.,Gray, Lloyd S.,Macdonald, Timothy L.
-
p. 3821 - 3839
(2007/10/03)
-
- Hypervalent iodine(III) sulfonate mediated synthesis of 5-benzoyldihydro-2(3H)-furan-one in ionic solvent
-
The room temperature ionic liquid, n-butylpyridinium tetrafluoroborate(BPyBF4) is used as a "green" recyclable solvent for the reaction of 4-benzoylbutyric acid with [hydroxy-(2,4-dinitrobenzenesulfonyloxy)iodo]-benzene (HDNIB) to prepare 5-benzoyldihydro-2(3H)-furanone.
- Hou, Rei-Sheu,Wang, Huey-Min,Lin, Yu-Chien,Chen, Ling-Chieg
-
p. 649 - 656
(2007/10/03)
-
- Derivatives of 4-hydroxybutanoic acid and of its higher homologue as ligands of γ(g)-hydroxybutyrate (ghb) receptors, pharmaceutical compositions containing same and pharmaceutical uses
-
The invention concerns the field of synthesis organic chemistry applied to the pharmaceutical field and concerns novel derivatives of 4-hydroxybutanoic acid and its higher homologue, 5-hydroxypentanoic acid, their crotonic homologues, pharmaceutical compo
- -
-
Page/Page column 6
(2010/02/11)
-
- COMPOUNDS AND COMPOSITIONS FOR DELIVERING ACTIVE AGENTS
-
Compounds and compositions for the delivery of active agents are provided. Methods of administration and preparation are provided as well.
- -
-
Page/Page column 80
(2010/02/14)
-
- (Phenylmethoxy)phenyl Derivatives of Ω-Oxo- and Ω-Tetrazolylalkanoic Acids and Related Tetrazoles. Synthesis and Evaluation as Leukotriene D4 Receptor Antagonists
-
Two series of (phenylmethoxy)phenyl compounds derived from the structure of LY163443 were synthesized and evaluated as leukotriene D4 receptor antagonists.In the Ω--Ω-oxoalkanoic acid series, 5-phenyl>-3,3-dimethyl-5-oxopentanoic acid (8) was the most potent antagonist of LTD4-induced contractions of guinea pig ileum (pKB of 7.60) and LTD4 pressor response in pithed rats (ED50 of 1.4 mg/kg iv).Replacing the carboxylic acid function with 5-tetrazole gave slightly more potent compounds.Inthe Ω-alkyl>tetrazolyl>alkanoic acid series, replacing the carboxylic acid with 5-tetrazole gave compounds that were equally effective in the guinea pig ileum but more potent in vivo against the LTD4 pressor response in rat.The pKB value in the guinea pig ileum for 1--2H-tetrazol-5-yl>methyl>phenoxy>methyl>phenyl>ethanone (25) was 7.87 and the ED50 for antagonism of the LTD4 pressor response was 4.0 mg/kg iv.The sodium salts of 8 (9) and 25(26) given by the iv route of administration antagonized LTD4-induced cardiovascular alterations in anesthetized rat and LTD4-induced bronchoconstriction in guinea pig in a dose-dependent manner.Oral activity was also demonstrated against the LTD4-induced bronchoconstriction in guinea pig.
- Dillard, Robert D.,Hahn, Richard A.,McCullough, Doris,Carr, F. Patrick,Rinkema, Lynn E.,et al.
-
p. 2768 - 2778
(2007/10/02)
-