- A metal-free strategy for the cross-dehydrogenative coupling of 1,3-dicarbonyl compounds with 2-methoxyethanol
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Here, we report a metal-free approach for the construction of methylene-bridged bis-1,3-dicarbonyl compounds via cross-dehydrogenative coupling of 1,3-dicarbonyl compounds with 2-methoxyethanol. In addition, we have extended this methodology to synthesize tetra-substituted pyridine derivatives using 1,3-dicarbonyl, 2-methoxyethanol and NH4OAc in one step. The key advantages include accepting a wide range of substrates, utilizing O2 as the sole oxidant, and synthesizing biologically active compounds such as 1,4-dihydropyridine and pyrazole. This journal is
- Chang, Yu-Lun,Huang, Sheng-Hua,Kudale, Vishal Suresh,Wang, Jeh-Jeng,Zheng, Sheng
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supporting information
p. 1226 - 1230
(2022/02/21)
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- Gold N-Heterocyclic Carbene Catalysts for the Hydrofluorination of Alkynes Using Hydrofluoric Acid: Reaction Scope, Mechanistic Studies and the Tracking of Elusive Intermediates
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An efficient and chemoselective methodology deploying gold-N-heterocyclic carbene (NHC) complexes as catalysts in the hydrofluorination of terminal alkynes using aqueous HF has been developed. Mechanistic studies shed light on an in situ generated catalyst, formed by the reaction of Br?nsted basic gold pre-catalysts with HF in water, which exhibits the highest reactivity and chemoselectivity. The catalytic system has a wide alkyl substituted-substrate scope, and stoichiometric as well as catalytic reactions with tailor-designed gold pre-catalysts enable the identification of various gold species involved along the catalytic cycle. Computational studies aid in understanding the chemoselectivity observed through examination of key mechanistic steps for phosphine- and NHC-coordinated gold species bearing the triflate counterion and the elusive key complex bearing a bifluoride counterion.
- Bédard, Sandrine,Cavallo, Luigi,Falivene, Laura,Gauthier, Rapha?l,Nolan, Steven P.,Paquin, Jean-Fran?ois,Saab, Marina,Tzouras, Nikolaos V.,Van Hecke, Kristof,Zhang, Ziyun
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supporting information
(2021/12/09)
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- A Carbene Strategy for Progressive (Deutero)Hydrodefluorination of Fluoroalkyl Ketones
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Hydrodefluorination is one of the most promising chemical strategies to degrade perfluorochemicals into partially fluorinated compounds. However, controlled progressive hydrodefluorination remains a significant challenge, owing to the decrease in the stre
- Bi, Xihe,Sivaguru, Paramasivam,Song, Qingmin,Wang, Zikun,Zanoni, Giuseppe,Zhang, Xiaolong,Zhang, Xinyu
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- Catalyst- And Substituent-Controlled Regio- And Stereoselective Synthesis of Indolyl Acrylates by Lewis-Acid-Catalyzed Direct Functionalization of 3-Formylindoles with Diazo Esters
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A facile and efficient In(OTf)3- and BF3·OEt2-catalyzed direct transformation of 3-formylindoles with diazo esters has been developed for synthesizing diverse and functionalized indolyl acrylates. This one-pot protocol furnishes various (Z)-α-hydroxy-β-indolyl acrylates, (E)-β-(2-alkoxy-2-oxoethoxy)-α-indolyl acrylates, and (Z)-3-hydroxy-2-indolyl acrylates by a catalyst- and substituent-controlled, regio- and stereoselective cascade reaction. The protocol has several advantages, including low loading of the catalyst, mild reaction conditions, broad scope, and high functional group tolerance. The synthesized compounds can be further converted into diversely functionalized materials.
- Jamshaid, Sana,Devkota, Shreedhar,Lee, Yong Rok
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supporting information
p. 2140 - 2146
(2021/04/05)
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- Access to gem-Dibromoenones Enabled by Carbon-Centered Radical Addition to Terminal Alkynes in Water Solution
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We herein report a novel and more practical approach to prepare gem-dibromoenones from terminal alkynes, tetrabromomethane (CBr4), and water in a single step. Mechanistic studies reveal that the generation of a tribromomethyl radical with the assistance of a persulfate salt (K2S2O8) is essential to this transformation. The reaction features readily available chemicals, a broad substrate scope, a green solvent, and mild reaction conditions, providing an efficient alternative for construction of halogen-substituted enones.
- Zeng, Xianghua,Xu, Yuhai,Liu, Jiawei,Deng, Yuanyuan
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p. 9058 - 9062
(2021/11/24)
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- Non-metal Lewis acid-catalyzed cross-Claisen condensation for β-keto esters
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In this work, we disclose a new catalytic and highly chemoselective cross-Claisen condensation of esters. In the presence of TBSNTf2 as a non-metal Lewis acid, various esters can undergo cross-Claisen condensation to form β-keto esters which are important building blocks. Compared with the traditional Claisen condensation, this process, employing silyl ketene acetals (SKAs) as carbonic nucleophiles to achieve cross-Claisen condensation, requires mild conditions and has good tolerance of functional groups. This journal is
- Han, Zhengyu,Huang, Hai,Meng, Fuliang,Yang, Zhenkun,Zhang, Tianyu,Zhou, Dapeng
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supporting information
p. 9163 - 9166
(2021/11/16)
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- Palladium catalysed hydrolysis-free arylation of aliphatic nitriles for the synthesis of 4-arylquinolin-2-one/pyrazolone derivatives
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Palladium catalysed addition of arylboronic acid to the readily available 2-cyano-(N-aryl)-acetamide or ethyl-2-cyanoacetate followed by subsequent reaction transform them into the biologically significant 4-arylquinolin-2-one or pyrazolone derivatives. The reaction conditions are robust enough to prevent the hydrolysis of ester/amide moiety during arylation. In addition, the unactivated nitrile moiety in the acetonitrile also converted to the corresponding acetophenone derivative.
- Krishna Reddy, Singarajanahalli Mundarinti,Prasanna Kumari, Subramaniyan,Selva Ganesan, Subramaniapillai
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- Amide/Ester Cross-Coupling via C-N/C-H Bond Cleavage: Synthesis of β-Ketoesters
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Activated primary, secondary, and tertiary amides were coupled with enolizable esters in the presence of LiHMDS to obtain good yields of β-ketoesters at room temperature. Notably, this protocol provides an efficient, mild, and high chemoselectivity method
- Chen, Jiajia,Joseph, Devaneyan,Xia, Yuanzhi,Lee, Sunwoo
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p. 5943 - 5953
(2021/04/02)
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- Ag-Catalyzed Insertion of Alkynyl Carbenes into C-C Bonds of β-Ketocarbonyls: A Formal C(sp2) Insertion
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Here we report a silver-catalyzed alkynyl carbene insertion into β-ketocarbonyls using alkynyl N-nosylhydrazones as alkynyl carbene precursors, which provides access to trisubstituted allenyl ketones. This reaction represents the first example of an alkynyl carbene insertion into a C-C σ bond, affording products homologated with an sp2 carbon center. The products are useful substrates for further transformations. Experimental investigations and theoretical calculations suggest the reaction proceeds through a stepwise enol cyclopropanation/retro-aldol pathway.
- Anderson, Edward A.,Bi, Xihe,Ning, Yongquan,Sivaguru, Paramasivam,Song, Qingmin,Wu, Lizuo
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supporting information
(2022/01/20)
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- PIKFYVE KINASE INHIBITORS
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The present invention relates to compounds useful as inhibitors of phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) as well as their use for treating diseases and disorders associated with PIKfyve.
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Page/Page column 208
(2021/08/20)
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- Electrochemical Oxidative Cyclization: Synthesis of Polysubstituted Pyrrole from Enamines
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A conceptually novel method for the preparation of pyrrole is described by electrochemical-oxidation-induced intermolecular annulation via enamines. In a simple undivided cell, based on a sodium acetate-facilitated, polysubstituted pyrrole derivations has been facilely synthesized under external oxidant-free condition. This electrosynthetic approach providing an environmentally benign protocol for C?C bond cross-coupling and oxidative annulation, which features unparalleled broad scope of substrates and practicality.
- Chen, Zhiwei,Shi, Guang,Tang, Wei,Sun, Jie,Wang, Wenxing
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supporting information
p. 951 - 955
(2021/02/03)
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- Construction of isoxazolone-fused phenanthridinesviaRh-catalyzed cascade C-H activation/cyclization of 3-arylisoxazolones with cyclic 2-diazo-1,3-diketones
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A Rh(iii)-catalyzed cascade C-H activation/intramolecular cyclization of 3-aryl-5-isoxazolones with cyclic 2-diazo-1,3-diketones was described, leading to the formation of isoxazolo[2,3-f]phenanthridine skeletons. The protocol features the simultaneous one-pot formation of two new C-C/C-N bonds and one heterocycle in moderate-to-good yields with good functional group compatibility. It is amenable to large-scale synthesis and further transformation.
- Hu, Wangcheng,He, Xinwei,Zhou, Tongtong,Zuo, Youpeng,Zhang, Shiwen,Yang, Tingting,Shang, Yongjia
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supporting information
p. 552 - 556
(2021/02/06)
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- Sulfur-controlled and rhodium-catalyzed formal (3 + 3) transannulation of thioacyl carbenes with alk-2-enals and mechanistic insights
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A rhodium-catalyzed denitrogenative formal (3 + 3) transannulation of 1,2,3-thiadiazoles with alk-2-enals is achieved, producing 2,3-dihydrothiopyran-4-ones in moderate to excellent yields. An inverse KIE of 0.49 is obtained, suggesting the reversibility of the oxidative addition of thioacyl Rh(i) carbenes to alk-2-enals. The late-stage structural modifications of steroid compounds are realized. Moreover, our studies show that thioacyl carbenes have different reactivities to those of α-oxo and α-imino carbenes, and highlight the importance of heteroatoms in deciding the reactivities of heterovinyl carbenes.
- Wu, Qiuyue,Dong, Ziyang,Xu, Jiaxi,Yang, Zhanhui
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supporting information
p. 3173 - 3180
(2021/04/21)
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- (E)-3-aryl-3-(2-methylhydrazino) propionate compound as well as preparation method and application thereof
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The invention provides an (E)-3-aryl-3-(2-methylhydrazino) propionate compound and a preparation method of the (E)-3-aryl-3-(2-methylhydrazino) propionate compound. According to the method, aryl ketone and diester carbonate are used as raw materials, aryl beta-keto ester compounds are prepared with high yield under the condition of weak reflux, then the aryl beta-keto ester compounds are reacted with p-methylbenzenesulfonyl hydrazide, and the (E)-3-aryl-3-(2-methylhydrazino) propionate compound is prepared with high yield and high regioselectivity. According to the preparation method, alcohols such as methanol and ethanol are used as solvents for reaction. The method has the characteristics of relatively mild reaction conditions, simplicity and convenience in operation, high regioselectivity, high yield and the like, and the synthesized (E)-3-aryl-3-(2-methylhydrazino) propionate compound can be used for preparing pyrazoline compounds.
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Paragraph 0044-0046
(2021/05/22)
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- Aromaticity-Driven Access to Cycloalkyl-Fused Naphthalenes
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We report the efficient synthesis of cycloalkyl-fused naphthalenes through the [4 + 2]-cycloaddtion/decarboxylative aromatization of alkyne-tethered aryne insertion adducts. These scaffolds were difficult to synthesize using conventional reactions. The reaction proceeds via the formation of a benzopyrylium intermediate followed by intramolecular [4 + 2] cycloaddition and a subsequent decarboxylation pathway. This method is also compatible with allene-tethered substrates to afford similar products. In addition, the one-pot synthesis of polysubstituted naphthalenes via aryne insertion/benzannulation has also been developed in good yield.
- Sanjeev, Karekar,Raju, Silver,Chandrasekhar, Srivari
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supporting information
p. 4013 - 4017
(2021/05/29)
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- Iridium-Catalyzed Enantioselective and Diastereoselective Hydrogenation of Racemic β’-Keto-β-Amino Esters via Dynamic Kinetic Resolution
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An iridium/f-diaphos catalytic system for the enantioselective hydrogenation of α-substituted β-ketoesters via dynamic kinetic resolution is reported. The desired anti β’-hydroxy-β-amino esters were obtained in moderate to good yields (60–95%) with 72–99% ees and 91:9 to 99:1 drs. This protocol tolerates various functional groups and could be easily conducted on gram scale with lower catalyst loading (TON up to 9100). (Figure presented.).
- He, Jiayin,Huang, An,Ling, Fei,Wang, Shiliang,Wang, Yifan,Wang, Ze,Zhao, Xianghua,Zhong, Weihui
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supporting information
p. 4714 - 4719
(2021/09/02)
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- Photoinduced Diverse Reactivity of Diazo Compounds with Nitrosoarenes
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A diverse reactivity of diazo compounds with nitrosoarene in an oxygen-transfer process and a formal [2 + 2] cycloaddition is reported. Nitosoarene has been exploited as a mild oxygen source to oxidize an in situ generated carbene intermediate under visible-light irradiation. UV-light-mediated in situ generated ketenes react with nitosoarenes to deliver oxazetidine derivatives. These operationally simple processes exemplify a transition-metal-free and catalyst-free protocol to give structurally diverse α-ketoesters or oxazetidines.
- Roy, Sourav,Kumar, Gourav,Chatterjee, Indranil
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supporting information
p. 6709 - 6713
(2021/09/08)
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- Iridium(III)-Catalyzed C(3)-H Alkylation of Isoquinolines via Metal Carbene Migratory Insertion
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An Ir(III)-catalyzed C(3)-H alkylation of N-acetyl-1,2-dihydroisoquinolines with diverse acceptor-acceptor diazo compounds has been achieved under a single catalytic system via metal carbene migratory insertion. Moreover, further synthetic transformations of the alkylated products such as aromatization, selective decarboxylation, and decarbonylation lead to the formation of several synthetically viable isoquinoline derivatives having immense potentials.
- Jha, Neha,Singh, Roushan Prakash,Saxena, Paridhi,Kapur, Manmohan
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supporting information
p. 8694 - 8698
(2021/11/24)
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- Synthetic method of lobeline hydrochloride
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The invention relates to the technical field of medicine synthesis, and particularly discloses a method for synthesizing lobeline hydrochloride. The method comprises the following steps: performing acylation reaction on ethyl acetoacetate and benzoyl chloride serving as raw materials in the presence of NaOH, NH4Cl and the like, performing hydrolysis reaction on the obtained ethyl benzoylacetate in water in the presence of potassium hydroxide to obtain benzoylacetic acid, carrying out a condensation reaction with glutaraldehyde and methylamine hydrochloride in a citric acid buffer solution, carrying out a reduction reaction on lobeline diketone hydrochloride obtained by the condensation reaction in a mixed solution composed of potassium borohydride, activated carbon, sodium hydroxide and methanol, quenching the reducing agent in the obtained reaction liquid by sulfuric acid, sequentially filtering, extracting, concentrating, cooling and crystallizing to obtain lobeline racemate, then adding L-DBTA, and sequentially performing resolution, dissociation and hydrochlorination to obtain lobeline hydrochloride. The synthesis method has the characteristics of few synthesis steps, simple synthesis conditions, convenience in operation and the like, and the used raw materials have the characteristics of wide source, low price and the like.
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-
Paragraph 0006; 0027; 0030; 0032; 0034
(2021/06/09)
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- Radical Aza-Cyclization of α-Imino-oxy Acids for Synthesis of Alkene-Containing N-Heterocycles via Dual Cobaloxime and Photoredox Catalysis
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Nitrogen-containing heterocycles are prevalent in both naturally and synthetically bioactive molecules. We report herein an unprecedented protocol for radical aza-cyclization of α-imino-oxy acids with pendant alkenes via synergistic photoredox and cobaloxime catalysis. With or without alkenes as the intermolecular cross-coupling partners, the transformation provides a variety of corresponding alkene-containing dihydropyrrole products in satisfactory yields. In the presence of external alkenes, the tandem reaction generates E-selective coupling products with excellent chemo- and stereoselectivity.
- Tu, Jia-Lin,Liu, Jia-Li,Tang, Wan,Su, Ma,Liu, Feng
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supporting information
p. 1222 - 1226
(2020/02/15)
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- Cu-Mediated Expeditious Annulation of Alkyl 3-Aminoacrylates with Aryldiazonium Salts: Access to Alkyl N2-Aryl 1,2,3-Triazole-carboxylates for Druglike Molecular Synthesis
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Alkyl N-aryl 1,2,3-triazole-carboxylates are important molecules or intermediates in medicinal chemistry, but the synthesis of N2-aryl counterparts remains elusive. Herein, we describe a Cu-mediated annulation reaction of alkyl 3-aminoacrylates with aryldiazonium salts, both of which are readily available substrates. Furthermore, alkyl 2-aminoacrylates are also viable substrates. Diverse alkyl N2-aryl 1,2,3-triazole-carboxylates and their analogues can be rapidly prepared under mild conditions. Especially, this protocol allows one to access several druglike variants of carbonic anhydrase inhibitors and celecoxib.
- Liu, Hao-Nan,Cao, Hao-Qiang,Cheung, Chi Wai,Ma, Jun-An
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supporting information
p. 1396 - 1401
(2020/02/22)
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- An efficient route for the synthesis of N-(1H-benzo[d]imidazol-2-yl)benzamide derivatives promoted by CBr4 in one pot
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A metal-free one-pot method for the synthesis of N-(1H-benzo[d]imidazol-2-yl)benzamide derivatives was proposed mediated by CBr4. The reaction went through ring formation and opening processes with only two protons leaving and the thermodynamically favorable products were selectively formed in moderate to good yields.
- Li, Songhua,Li, Yunyi,Ma, Chen,Xie, Caixia
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- Design, Synthesis, and Biochemical Characterization of Non-Native Antagonists of the Pseudomonas aeruginosa Quorum Sensing Receptor LasR with Nanomolar IC50 Values
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Quorum sensing (QS), a bacterial cell-to-cell communication system mediated by small molecules and peptides, has received significant interest as a potential target to block infection. The common pathogen Pseudomonas aeruginosa uses QS to regulate many of its virulence phenotypes at high cell densities, and the LasR QS receptor plays a critical role in this process. Small molecule tools that inhibit LasR activity would serve to illuminate its role in P. aeruginosa virulence, but we currently lack highly potent and selective LasR antagonists, despite considerable research in this area. V-06-018, an abiotic small molecule discovered in a high-throughput screen, represents one of the most potent known LasR antagonists but has seen little study since its initial report. Herein, we report a systematic study of the structure-activity relationships (SARs) that govern LasR antagonism by V-06-018. We synthesized a focused library of V-06-018 derivatives and evaluated the library for bioactivity using a variety of cell-based LasR reporter systems. The SAR trends revealed by these experiments allowed us to design probes with 10-fold greater potency than that of V-06-018 and 100-fold greater potency than other commonly used N-acyl-l-homoserine lactone (AHL)-based LasR antagonists, along with high selectivities for LasR. Biochemical experiments to probe the mechanism of antagonism by V-06-018 and its analogues support these compounds interacting with the native ligand-binding site in LasR and, at least in part, stabilizing an inactive form of the protein. The compounds described herein are the most potent and efficacious antagonists of LasR known and represent robust probes both for characterizing the mechanisms of LuxR-type QS and for chemical biology research in general in the growing QS field.
- Blackwell, Helen E.,Manson, Daniel E.,Nyffeler, Kayleigh E.,O'Reilly, Matthew C.
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- Double Enzyme-Catalyzed One-Pot Synthesis of Enantiocomplementary Vicinal Fluoro Alcohols
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A double-enzyme-catalyzed strategy for the synthesis of enantiocomplementary vicinal fluoro alcohols through a one-pot, three-step process including lipase-catalyzed hydrolysis, spontaneous decarboxylative fluorination, and subsequent ketoreductase-catalyzed reduction was developed. With this approach, β-ketonic esters were converted to the corresponding vicinal fluoro alcohols with high isolated yields (up to 92percent) and stereoselectivities (up to 99percent). This new cascade process addresses some issues in comparison with traditional methods such as environmentally hazardous reaction conditions and low stereoselectivity outcome.
- Fan, Jiajie,Lin, Xianfu,Peng, Yongzhen,Wang, Anlin,Wu, Qi,Xu, Jian,Xu, Weihua,Yu, Huilei
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supporting information
(2020/07/24)
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- Desymmetrization of meso-dicarbonatecyclohexene with β-Hydrazino carboxylic esters via a Pd-catalyzed allylic substitution cascade
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The desymmetrization of meso-dicarbonatecyclohexene with β-hydrazino carboxylic esters has been achieved via a RuPHOX/Pd-catalyzed allylic substitution cascade for the construction of chiral hexahydrocinnoline derivatives with high performance. Mechanistic studies reveal that the reaction exploits a pathway different from that of our previous work and that the first nitrogen nucleophilic process is the rate-determining step. The protocol could be conducted on a gram scale without any loss of catalytic behavior, and the corresponding chiral hexahydrocinnolines can undergo diverse transformations.
- Xu, Kai,Zheng, Yan,Ye, Yong,Liu, Delong,Zhang, Wanbin
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supporting information
p. 8836 - 8841
(2020/11/30)
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- Direct synthesis of 2,3,5-trisubstituted pyrroles: via copper-mediated one-pot multicomponent reaction
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We have developed a copper-mediated one-pot synthesis of 2,3,5-trisubstituted pyrroles from 1,3-dicarbonyl compounds and acrylates using ammonium acetate as a nitrogen source. The reaction achieves C-C and C-N bond formation and provides an efficient approach to access highly functionalized pyrroles without further raw material preparation. This method is operationally simple, compatible with a wide range of functional groups, and provides the target products in moderate to good yields. This journal is
- He, Jian-Ping,Huang, Guo-Sheng,Luo, Nan,Zhan, Zhen-Zhen,Zhang, Ming-Ming
-
supporting information
p. 9831 - 9835
(2021/01/05)
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- Catalytic Mechanism Study on the 1,2- and 1,4-Transfer Hydrogenation of Ketimines and β-Enamino Esters Catalyzed by Axially Chiral Biscarboline-Based Alcohols
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Axial N-O alcohols, which have two large carboline moieties connected to the axis were synthesized and used in catalytic enantioselective 1,2- and 1,4-transfer hydrogenations of total 26 ketimines and β-enamino esters. Excellent levels of enantioselectivity ranging from 91% to 99% were achieved by using catalyst (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. Interestingly, a mixture of (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide and (aR)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide was also able to provide high enantioselectivities up to 95% that is the same as that using pure (aS)-(S)-3,3′-bis((S)-2-(hydroxymethyl)pyrrolidine-1-carbonyl)-9,9′-dimethyl-9H,9′H-[1,1′-bipyrido[3,4-b]indole] 2-oxide. A plausible catalytic mechanism was suggested and total four kinds of transition states (TS) including almost 60 TS structures were investigated using density functional theory (DFT) with different basis sets such as 6-311G(2d,p). The predicted activation energy data are consistent with the experimental results. (Figure presented.).
- Dong, Mengxian,Wang, Jie,Wu, Shijie,Zhao, Yang,Ma, Yangyang,Xing, Yongfei,Cao, Fei,Li, Longfei,Li, Zhenqiu,Zhu, Huajie
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supporting information
p. 4602 - 4610
(2019/08/30)
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- Catalytic Asymmetric Epoxidation of Aldehydes with Two VANOL-Derived Chiral Borate Catalysts
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A highly diastereo- and enantioselective method for the epoxidation of aldehydes with α-diazoacetamides has been developed with two different borate ester catalysts of VANOL. Both catalytic systems are general for aromatic, aliphatic, and acetylenic aldehydes, giving high yields and inductions for nearly all cases. One borate ester catalyst has two molecules of VANOL and the other only one VANOL. Catalysts generated from BINOL and VAPOL are ineffective catalysts. An application is shown for access to the side-chain of taxol.
- Gupta, Anil K.,Yin, Xiaopeng,Mukherjee, Munmun,Desai, Aman A.,Mohammadlou, Aliakbar,Jurewicz, Kelsee,Wulff, William D.
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supporting information
p. 3361 - 3367
(2019/02/16)
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- Mild Cu-Catalyzed Oxidation of Benzylic Boronic Esters to Ketones
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The oxidation of benzylic boronic esters directly to the ketone is reported. This mild Cu-catalyzed method uses an ambient atmosphere of air as the terminal oxidant and is notably chemoselective. Oxidation of the C-B bond occurs selectively, even in the presence of unprotected alcohols. Initial investigation suggests the reaction proceeds through an alkylboron to Cu transmetalation, peroxide formation, and rearrangement to give the carbonyl.
- Grayson, James D.,Partridge, Benjamin M.
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p. 4296 - 4301
(2019/05/14)
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- N-hydroxyl-5-substituted-1H-pyrazol-3-formamide compound as well as preparation method and use thereof
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The invention belongs to the field of medicine chemistry, and particularly relates to an N-hydroxyl-5-substituted-1H-pyrazol-3-formamide compound as well as a preparation method and use thereof. The specific structure of the compound is as shown in a formula I. The invention also provides a synthesis method of the compound in the formula I and inhibition activity thereof for acidic sphingomyelinase. The compound can be used for developing drugs for treating atherosclerosis (AS), diabetes, emphysema, pulmonary edema, pulmonary fibrosis, cystic fibrosis, chronic obstructive pulmonary disease, pulmonary arterial hypertension, non-alcoholic fatty liver disease, Alzheimers (AD), multiple sclerosis (MS), cerebral stroke and depression diseases. (the formula I is shown in the description).
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Paragraph 0024; 0025; 0026; 0027
(2019/02/03)
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- Synthesis and biochemical evaluation of lid-open D-amino acid oxidase inhibitors
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Most of the known inhibitors of D-amino acid oxidase (DAAO) are small polar molecules recognized by the active site of the enzyme. More recently a new class of DAAO inhibitors has been disclosed that interacts with loop 218?224 at the top of the binding pocket. These compounds have a significantly larger size and more beneficial physicochemical properties than most reported DAAO inhibitors, however, their structure-activity relationship is poorly explored. Here we report the synthesis and evaluation of this type of DAAO inhibitors that open the lid over the active site of DAAO. In order to collect relevant SAR data we varied two distinct parts of the inhibitors. A systematic variation of the pendant aromatic substituents according to the Topliss scheme resulted in DAAO inhibitors with low nanomolar activity. The activity showed low sensitivity to the substituents investigated. The variation of the linker connecting the pendant aromatic moiety and the acidic headgroup revealed that the interactions of the linker with the enzyme were crucial for achieving significant inhibitory activity. Structures and activities were analyzed based on available X-ray structures of the complexes. Our findings might support the design of drug-like DAAO inhibitors with advantageous physicochemical properties and ADME profile.
- Szilágyi, Bence,Hargitai, Csilla,Kelemen, ádám A.,Rácz, Anita,Ferenczy, Gy?rgy G.,Volk, Balázs,Keser?, Gy?rgy M.
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supporting information
(2019/01/31)
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- A kind of benzofuran and benzofuran coumarin derivative and its preparation method and application (by machine translation)
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The invention discloses a formula (I), (II), (III), (IV) shown benzofurans and Coumestans derivative and its preparation method, and said styrene and furan and Coumestans derivative compound in the treatment of multi-drug resistant tuberculosis disease in the application. The invention surfactant and furan and Coumestans derivatives are a class of novel structure, the bacteriostatic effect is prominent anti-Mycobacterium tuberculosis compound, it is to Mycobacterium tuberculosis pks13 gene fragment encoding polyketide synthase as the acting target, inhibit the growth and reproduction of microorganisms, in particular inhibiting Mycobacterium tuberculosis in bacterial cell wall synthesis of branch, in the medical field has potential application prospect. (by machine translation)
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Paragraph 0088; 0089
(2019/07/10)
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- Benzoyl acid ethyl ester preparation method (by machine translation)
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A benzoyl acid ethyl ester preparation method, characterized in that comprises the following steps: step (1): in the non-proton solvent, adding a weak inorganic base, slowly adding acetyl ethyl acetate, then dropwise benzoyl chloride reaction; step (2): add the strong inorganic base to carry out the reaction, after the reaction, filtration, shall be benzoyl ethyl acetate, the filtrate is distilled, the recovered solvent is recycled; wherein in the in the whole reaction process, does not add the aqueous reagent. The method of the whole in the preparation of waste water and gas produced, only a small amount of residue are produced, and environmental protection. Prepared by the method of the benzoyl ethyl acetate purity>94%, yield>99%, and the equipment requirement is low, and is suitable for large-scale industrial production. (by machine translation)
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Paragraph 0007; 0034-0053
(2018/05/01)
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- Development of 2-arylbenzo[: H] quinolone analogs as selective CYP1B1 inhibitors
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The CYP1B1 enzyme is regarded as a potential target for cancer prevention and therapy. Based on the structure of α-naphthoflavone (ANF), diverse 2-arylbenzo[h]quinolone derivatives were designed, synthesized and evaluated as selective CYP1B1 inhibitors. Compared with ANF, although few of the title compounds possessed comparable or slightly higher CYP1B1 inhibitory activity, these compounds displayed a significantly increased selectivity toward CYP1B1 over CYP1A2. Among them compounds 5e, 5g and 5h potently inhibited the activity of CYP1B1 with IC50 values of 3.6, 3.9 and 4.1 nM respectively, paralleled by an excellent selectivity profile. On the basis of predicted clogP values, these target compounds may exhibit improved water-solubility compared to ANF. In particular, 5h showed a great superiority in the reversal of CYP1B1-mediated docetaxel resistance in vitro. The current study may serve as a good starting point for the further development of more potent as well as specific CYP1B1 inhibitors capable of reversing CYP1B1-mediated anticancer-drug resistance.
- Dong, Jinyun,Wang, Zengtao,Meng, Qingqing,Zhang, Qijing,Huang, Guang,Cui, Jiahua,Li, Shaoshun
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p. 15009 - 15020
(2018/04/30)
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- Pyrazole alcohol compound, pharmaceutical composition thereof and application thereof to drugs
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The invention discloses a 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound, a tautomer thereof, a pharmaceutical composition thereof and application thereof to drugs. The 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound has double effects of resisting platelet aggregation and protecting nerve cells, and comprises a compound as shown in the formula (I), a tautomer (Ia) thereof, or a stereoisomer, a geometrical isomer, a hydrate or a solvate thereof, or a pharmaceutically acceptable salt or prodrug as shown in the description. The 1-(3,5,6-trimethyl pyrazine-2-yl)-5-pyrazole alcohol compound and the pharmaceutical composition thereof provided by the invention can be used for preparing drugs for prevention and/or treatment and/or auxiliary treatment of cerebral apoplexy, cardiovascular and cerebrovascular diseases, senile dementia and complications thereof caused by thrombosis and excessive free radicals.
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Paragraph 0128; 0133
(2018/10/19)
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- Substituted phenyl pyrazolone derivatives and preparation and application (by machine translation)
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The present invention provides a substituted phenyl pyrazolone derivatives, in particular to a 2 - phenyl - pyrazoline - 3 - ketone compound and its pharmaceutically acceptable salt, solvate. The substituted acetic acid ethyl ester with sodium hydroxide in aqueous solution in the [...] reflux reaction, then in the palladium-carbon and hydrogen under the action of the hydrogenolysis benzyl, phenyl [...] obtained, with the bromochlorodifluoromethane alkane reaction to obtain the chloro, finally with the secondary amine on the condensation to obtain the target compound. The invention substituted phenyl pyrazoline compounds in vitro exhibits excellent capability of eliminating the free radicals, and have more strongly inhibit H3 receptor activity, exhibits excellent penetration of the blood brain barrier capacity, has a unique dual active, therefore, its for cerebral apoplexy, Alzheimer's disease, Parkinson's disease, progressive neurodegenerative diseases such as frozen sickness treatment has a unique clinical effect. The compound of the invention for treating central system system related disease and inflammatory disease application of the medicament. The formula structure is as follows: (by machine translation)
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Paragraph 0034; 0039; 0040
(2019/01/08)
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- BINOL derivatives with aggression-induced emission
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As fluorescent probes, the small Stokes shift and ACQ effect limit the application of BINOL derivatives. Herein, a new series of BINOL derivatives were synthesized which could be turned from ACQ to AIE fluorophores by changing the electron withdrawing group. Among these compounds, BIN-COP exhibits an obvious AIE property with low cytotoxicity. The bioimaging performance indicated that the designed fluorophores could be successfully used for bioimaging.
- Shi, Lei,Li, Kun,Cui, Peng-Cheng,Li, Ling-Ling,Pan, Sheng-Lin,Li, Meng-Yang,Yu, Xiao-Qi
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supporting information
p. 4413 - 4416
(2018/07/25)
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- In situ generation of nitrile oxides from copper carbene and tert -butyl nitrite: Synthesis of fully substituted isoxazoles
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Herein, we present a novel [3 + 2] cycloaddition reaction of β-keto esters with nitrile oxides, which were generated in situ from copper carbene and tert-butyl nitrite. This three-component reaction provides new methodology for the direct synthesis of fully substituted isoxazole derivatives, featuring mild reaction conditions, readily accessible starting materials and simple operation. The experimental studies and DFT calculations suggest that the reaction starts with the generation of the key intermediate nitrile oxides, followed by a [3 + 2] cycloaddition reaction of β-keto esters to give the final isoxazole products.
- Chen, Rongxiang,Ogunlana, Abosede Adejoke,Fang, Shangwen,Long, Wenhao,Sun, Hongmei,Bao, Xiaoguang,Wan, Xiaobing
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supporting information
p. 4683 - 4687
(2018/07/06)
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- Iridium-Catalyzed Asymmetric Hydrogenation of Tetrasubstituted α-Fluoro-β-enamino Esters: Efficient Access to Chiral α-Fluoro-β-amino Esters with Two Adjacent Tertiary Stereocenters
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An iridium-catalyzed highly efficient asymmetric hydrogenation of challenging tetrasubstituted α-fluoro-β-enamino esters was successfully developed using bisphosphine-thiourea (ZhaoPhos) as the ligand, which prepared a series of chiral α-fluoro-β-amino esters containing two adjacent tertiary stereocenters with high yields and excellent diastereoselectivities/enantioselectivities (73%-99% yields, >25:1 dr, 91%>99% ee, and turnover number (TON) values up to 8600), and no defluorinate byproduct was detected.
- Han, Zhengyu,Guan, Yu-Qing,Liu, Gang,Wang, Rui,Yin, Xuguang,Zhao, Qingyang,Cong, Hengjiang,Dong, Xiu-Qin,Zhang, Xumu
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supporting information
p. 6349 - 6353
(2018/10/15)
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- 7-substituted-4-aryl coumarins compound, and preparation method and application thereof
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The invention discloses a 7-substituted-4-aryl coumarins compound, and a preparation method and an application thereof and belongs to the technical field of antitumor drugs. The 7-substituted-4-aryl coumarins compound is acquired in the manner of modifying and remolding 4 and 7 loci of the coumarins. The structural formula is shown in the specification. A pharmacological experiment proves that such a compound has an excellent antitumor activity, can be used for preparing the antitumor drugs, is capable of supplying a new selection for the development and application of the antitumor drugs and further can be applied to the design and optimization of the antitumor drugs. The preparation method of the compound has the advantages of easily acquired raw materials, mild reaction condition, easily realized synthesis method, simple reaction process and operation, low-cost reagents and higher yield.
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Paragraph 0040; 0041; 0042
(2017/08/02)
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- KF/Nano-clinoptilolite Catalyzed Aldol-Type Reaction of Aldehydes with Ethyl Diazoacetate
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Abstract: Potassium fluoride supported on nano-clinoptilolite (KF/CP NPs) was used as an excellent catalytic system for direct aldol-type condensation of aldehydes with ethyl diazoacetate under solvent-less conditions. A variety of α-diazo carbonyl derivatives were prepared in good to excellent yields in short reaction times. Graphical Abstract: [Figure not available: see fulltext.]
- Balou, Javad,Khalilzadeh, Mohammad A.,Zareyee, Dariush
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p. 2612 - 2618
(2017/09/06)
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- A Direct, Versatile, and Chemoselective Synthesis of Vinylogous Bis- and Monourethanes/amides and β-Keto Esters by Aza-Knoevenagel-Type Reactions of Tertiary Amides with Enolates
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Full details of our investigations into aza-Knoevenagel-type reactions with common tertiary amides as the electrophilic partner are reported. The method is based on the addition of stabilized carbanionic nucleophiles to the amides, which are activated in situ with triflic anhydride (Tf2O). The reaction proceeds under mild conditions and tolerates several sensitive functional groups including enamide and tert-butyldimethylsilyloxy (TBSO) groups. Significantly, with amides bearing more reactive ester, cyano, and aldehyde groups, the reaction occurs chemoselectively at the least reactive amide group. Such “umpolung” of the chemoselectivity in C=C bond formation is challenging, rare, and of synthetic value. Vinylogous bis-urethanes (aza-Knoevenagel-type condensation products), vinylogous urethanes, and vinylogous amides can be synthesized by employing enolates/carbanions generated from methyl ketones, malonic acid monoester, 2-phenylacetate, or (benzylsulfonyl)benzene. Moreover, when higher homologues of acetate were used, β-keto esters were obtained directly from amides. The method has been applied to the one-step syntheses of several known key intermediates in the total syntheses of alkaloids and 4-quinolone antibiotics. An efficient and mild intramolecular Friedel–Crafts-type cyclization of an anilinyl ester has also been achieved with Tf2O as an effective promoter. This amide-based method is a direct and umpoled alternative to the versatile but stepwise one based on thionation and the Eschenmoser sulfide contraction.
- Huang, Pei-Qiang,Ou, Wei
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p. 582 - 592
(2017/02/05)
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- Photocaged Hydrocarbons, Aldehydes, Ketones, Enones, and Carboxylic Acids and Esters that Release by the Norrish II Cleavage Protocol and Beyond: Controlled Photoinduced Fragrance Release
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Five families of caged fragrance compounds that allow the storage and release of the following small volatile organic molecules are described: terpene hydrocarbons, aldehydes, ketones, Michael-type α,β-unsaturated enones, and carboxylic acids and esters. These caged molecules are released by photoexcitation via carbonyl-directed hydrogen-transfer processes and subsequent C-C bond cleavage (Norrish Type II) or by didenitrogenation of diazirines.
- Griesbeck, Axel G.,Porschen, Bj?rn,Kropf, Christian,Landes, Agnieszka,Hinze, Olga,Huchel, Ursula,Gerke, Thomas
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p. 539 - 553
(2017/01/25)
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- PyrazoIoquinoline derivative, and preparation method and application thereof
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The invention relates to a pyrazoloquinoline derivative, and a preparation method and an application thereof. The pyrazoloquinoline derivative provided by the invention can be used as an electron/hole transporting material and a illuminant, has strong fluorescence in a liquid and a solid film, can form good amorphous film, and has pretty good heat and light stabilities at the same time.
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Paragraph 0049; 0050; 0051
(2017/07/22)
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- Asymmetric synthesis of (6R)-4-hydroxy-6-substituted-δ-lactones
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A novel approach for the asymmetric synthesis of (6R)-4-hydroxy-6-substituted-δ-lactones has been achieved using asymmetric reduction of a prochiral ketone in the presence of (S)-(?)-diphenyl-prolinol/borane as a key step. The enantiomeric purity of the products was determined by chiral GC.
- Gaikwad, Ravindra D.,Rane, Monica D.,Bhat, Sujata V.
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p. 181 - 185
(2017/01/11)
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- Rhodium-catalyzed asymmetric hydrogenation of tetrasubstituted β-acetoxy-α-enamido esters and efficient synthesis of droxidopa
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A rhodium-catalyzed asymmetric hydrogenation of challenging tetrasubstituted β-acetoxy-α-enamido esters was developed, giving chiral β-acetoxy-α-amido esters in high yields with excellent enantioselectivities (up to >99% ee). The products could be easily transformed to β-hydroxy-α-amino acid derivatives which are valuable chiral building blocks and a novel route for the synthesis of droxidopa was also developed.
- Guan, Yu-Qing,Gao, Min,Deng, Xu,Lv, Hui,Zhang, Xumu
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supporting information
p. 8136 - 8139
(2017/07/24)
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- Nickel-catalyzed enantioselective hydrogenation of β-(acylamino)acrylates: Synthesis of chiral β-amino acid derivatives
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The nickel-catalyzed asymmetric hydrogenation of β-(acylamino)acrylates has been developed, affording chiral β-amino acid derivatives with excellent yields (95-99% yield) and enantioselectivities (97-99% ee). With the Ni-Binapine system, high enantioselectivities (98-99% ee) have also been obtained in the hydrogenation of Z/E isomeric mixtures of β-alkyl and β-aryl β-(acylamino)acrylates. The synthesis of chiral β-amino acid derivatives on a gram scale has also been achieved with 0.2 mol % catalyst loading.
- Li, Xiuxiu,You, Cai,Li, Shuailong,Lv, Hui,Zhang, Xumu
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supporting information
p. 5130 - 5133
(2017/11/06)
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- Bromide-Mediated C-H Bond Functionalization: Intermolecular Annulation of Phenylethanone Derivatives with Alkynes for the Synthesis of 1-Naphthols
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Bromide-mediated intermolecular annulation of phenylethanone derivatives with alkynes has been developed, which allows for the regioselective formation of polysubstituted 1-naphthols. The usage of readily available bromine catalyst, broad substrate scope, and mild conditions make this protocol very practical. Mechanistic investigations reveal that the bromination of phenylethanone derivatives occurs to yield bromo-substituted intermediates, which react in situ with alkynes to furnish the desired 1-naphthols.
- Lu, Tao,Jiang, Ya-Ting,Ma, Feng-Ping,Tang, Zi-Jing,Kuang, Liu,Wang, Yu-Xuan,Wang, Bin
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supporting information
p. 6344 - 6347
(2017/12/08)
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- Internal Alkyne Regio- and Chemoselectivity using a Zwitterionic N-Heterocyclic Carbene Gold Catalyst in a Silver-Free Alkyne Hydration Reaction
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An alkyne hydration of terminal and internal alkynes is reported using a zwitterionic N-heterocyclic carbene gold catalyst [(BNHC)Au(SMe2)] in the absence of silver and Br?nsted acid additives. The hydration demonstrates good regioselectivity in alkyne hydration and chemoselectivity for internal alkynes vs. terminal. In addition, (BNHC)Au(SMe2) performs a propargyl alcohol hydration to predominantly form α-hydroxymethyl ketone over the more common Meyer–Schuster rearrangement product. While complex (BNHC)Au(SMe2) is active without silver additives, addition of silver hexafluoroantimonate (AgSbF6) increases reaction rate and decreases selectivity for internal alkyne hydration over terminal substrates. To the best of our knowledge, the rate enhancement of (BNHC)Au(SMe2) by AgSbF6is the first such demonstration of a silver effect for a “halide-free” Au catalyst. (Figure presented.).
- Weerasiri, Kushan C.,Chen, Danmin,Wozniak, Derek I.,Dobereiner, Graham E.
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p. 4106 - 4113
(2016/12/30)
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- Variations on the Blaise Reaction: Synthesis of 3,5-Dioxopentanoates and 3-Amino-5-oxopent-3-enoates
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We have achieved a facile and convenient synthesis of a variety of 3,5-dioxopentanoates (3,5-diketo esters) and 3-amino-5-oxopent-3-enoates by a zinc-mediated condensation of readily available 3-oxopropanenitriles (α-cyano ketones) with ethyl bromoacetate. The reaction is a variation on the classical Blaise reaction, tuned to the synthesis of trifunctional compounds having 3,5-diketo ester or 3-enamino 5-keto ester functional groups. Our studies revealed that the Blaise reaction on the nitrile occurs in preference to the Reformatsky reaction on the neighboring ketone when the two functional groups are in a geminal relationship, as found in α-cyano ketones, possibly due to zinc complexation leading to increased electrophilicity of the nitrile.
- Rao, H. Surya Prakash,Muthanna, Nandurka
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supporting information
p. 2014 - 2018
(2016/08/09)
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