- Inhibition of Autophagy by a Small Molecule through Covalent Modification of the LC3 Protein
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The autophagic ubiquitin-like protein LC3 functions through interactions with LC3-interaction regions (LIRs) of other autophagy proteins, including autophagy receptors, which stands out as a promising protein–protein interaction (PPI) target for the intervention of autophagy. Post-translational modifications like acetylation of Lys49 on the LIR-interacting surface could disrupt the interaction, offering an opportunity to design covalent small molecules interfering with the interface. Through screening covalent compounds, we discovered a small molecule modulator of LC3A/B that covalently modifies LC3A/B protein at Lys49. Activity-based protein profiling (ABPP) based evaluations reveal that a derivative molecule DC-LC3in-D5 exhibits a potent covalent reactivity and selectivity to LC3A/B in HeLa cells. DC-LC3in-D5 compromises LC3B lipidation in vitro and in HeLa cells, leading to deficiency in the formation of autophagic structures and autophagic substrate degradation. DC-LC3in-D5 could serve as a powerful tool for autophagy research as well as for therapeutic interventions.
- Chen, Kaixian,Chen, Zhifeng,Dang, Yongjun,Ding, Hong,Fan, Shijie,Hu, Junchi,Jiang, Hualiang,Li, Lianchun,Li, Quanfu,Lin, Tingting,Lu, Junyan,Luo, Cheng,Otomo, Chinatsu,Otomo, Takanori,Tan, Minjia,Tao, Hongru,Wan, Wei,Wen, Yi,Xie, Yuli,Xu, Pan,Yao, Zhiyi,Yue, Liyan,Zhang, Bidong,Zhang, Naixia,Zhang, Yuanyuan,Zhou, Bing,Zhu, Mingrui
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supporting information
p. 26105 - 26114
(2021/11/09)
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- Construction of Multiple-Substituted Chiral Cyclohexanes through Hydrogenative Desymmetrization of 2,2,5-Trisubstituted 1,3-Cyclohexanediones
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The construction of chiral multiple-substituted cyclohexanes motifs is a challenging topic in organic synthesis. By the combination of desymmetrization and remote stereocontrol, a ruthenium-catalyzed transfer hydrogenative desymmetrization of 2,2,5-trisubstituted 1,3-cyclohexanediones has been successfully developed for the construction of chiral multiple-substituted cyclohexanes with high enantioselectivity and diastereoselectivity. When an ester group was introduced to the two-position, a hydrogenative desymmetrization/transesterification cascade occurred, affording the bicyclic lactones bearing three stereocenters, including two discrete stereocenters and one quaternary stereogenic center, with high enantioselectivity. The products are the multiple-substituted chiral cyclohexanes bearing the hydroxyl and carbonyl functional groups, which provide a new opportunity for further precise elaboration.
- Yu, Chang-Bin,Song, Bo,Chen, Mu-Wang,Shen, Hong-Qiang,Zhou, Yong-Gui
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supporting information
p. 9401 - 9404
(2019/11/28)
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- Iodine-Promoted Semmler–Wolff Reactions: Step-Economic Access to meta-Substituted Primary Anilines via Aromatization
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An atom- and step-economic access to an array of unprotected meta-substituted primary anilines was disclosed using the Semmler–Wolff reaction, promoted by molecular iodine. Therein, noble metal catalysts and inert atmosphere are unnecessary while the forcing reaction conditions and the lengthy synthesis can be avoided. The synthetic utility of this approach is evident in the de novo syntheses of three bioactive molecules with good total yields.
- Wang, Shi-Ke,You, Xia,Zhao, Da-Yuan,Mou, Neng-Jie,Luo, Qun-Li
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supporting information
p. 11757 - 11760
(2017/09/07)
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- Dehydrogenative Formation of Resorcinol Derivatives Using Pd/C-Ethylene Catalytic System
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The conversion of substituted 1,3-cyclohexanediones to the alkyl ethers of resorcinol using a Pd/C-ethylene system is reported. In these reactions, ethylene works as a hydrogen acceptor. The efficient synthesis of resveratrol was achieved using this protocol as a key step. In addition, the direct formation of substituted resorcinols was carried out by adding K2CO3 into the reaction media.
- El-Deeb, Ibrahim Yussif,Funakoshi, Tatsuya,Shimomoto, Yuya,Matsubara, Ryosuke,Hayashi, Masahiko
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p. 2630 - 2640
(2017/03/14)
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- Synthesis of new 3-phenyl substituted dibenzo-1,4-diazepin-1-one derivatives
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A new series of 3-phenyl substituted dibenzo-1,4-diazepin-1-one derivatives were synthesised by condensation of 5-phenylcyclohexane-1,3-dione, o-phenylenediamine and benzaldehydes. All the compounds were characterised by IR, MS, 1H NMR and elemental analysis. The crystal structure of 3-phenyl-11-(2-chlorophenyl)-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e] [1,4]diazepin-1-one was determined by X-ray single-crystal diffraction.
- Wang, Fang-Ming,Bao, Dan,Wang, Ming,Li, Ming-Jun,Chen, Li-Zhuang,Han, Guang-Fan
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p. 664 - 667
(2015/02/18)
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- High-Yielding Total Synthesis of Sexually Deceptive Chiloglottones and Antimicrobial Dialkylresorcinols through an Organocatalytic Reductive Coupling Reaction
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Biologically important, less-explored natural products of sexually deceptive chiloglottones, antimicrobial dialkylresorcinols, and their many analogues were synthesized in very good yields in a sequential two-pot manner by using an "organocatalytic reductive coupling reaction" as the key step. Sexually deceptive chiloglottones, antimicrobial dialkylresorcinols, and their many analogues are synthesized in very good yields in a sequential two-pot manner by using an "organocatalytic reductive coupling reaction" as the key step.
- Madhavachary, Rudrakshula,Ramachary, Dhevalapally B.
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supporting information
p. 7317 - 7323
(2016/02/20)
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- One-pot synthesis of fused pyrroles through a key gold-catalysis-triggered cascade
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A two-step, one-pot synthesis of fused pyrroles is realized by firstly condensing an N-alkynylhydroxammonium salt with a readily enolizable ketone under mild basic conditions and then subjecting the reaction mixture to a gold catalyst, which triggers a cascade reaction involving a facile initial [3.3]-sigmatropic rearrangement of the gold-catalysis product, that is, an N,O-dialkenylhydroxamine. The reaction provides a facile access to polycyclic pyrroles in moderate to good yields. A two-step, one-pot synthesis of fused pyrroles is realized by firstly condensing an N-alkynylhydroxammonium salt with a readily enolizable ketone under mild basic conditions and then subjecting the reaction mixture to a gold catalyst, which triggers a cascade reaction involving a facile initial [3.3]-sigmatropic rearrangement of the gold-catalysis product, that is, an N,O-dialkenylhydroxamine. The reaction provides a facile access to polycyclic pyrroles in moderate to good yields (see scheme). Copyright
- Zheng, Zhitong,Tu, Huangfei,Zhang, Liming
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supporting information
p. 2445 - 2448
(2014/03/21)
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- Synthesis of 10-amino-9-aryl-2,3,4,5,6,7,9,10-octahydroacridine- 1,8-dione derivatives
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A series of novel 10-amino-9-aryl-2,3,4,5,6,7,9,10-octahydroacridine-1,8- dione derivatives 4 were synthesized by hydrazine or phenylhydrazine and 9-aryl-1,8-dioxo-2,3,4,5,6,7,9-heptahydroxanthene derivatives 3, which were prepared by 5-substituted-1,3-cyclohexanedione 1 and aromatic aldehydes 2 in the presence of concentrated H2SO4 as a catalyst in water. The structures of all compounds were characterized by IR, MS, 1H-NMR, and elemental analysis, and the title compounds possess good fluorescence properties..
- Han, Guang-Fan,Cui, Bin,Chen, Li-Zhuang,Hu, Xiao-Lei
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scheme or table
p. 195 - 199
(2012/04/17)
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- Tandem reactions leading to benzo[c]chromen-6-ones and 3-substituted isocoumarins
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A simple and convenient protocol for the synthesis of benzo[c]chromen-6- ones and 3-substituted isocoumarins through a CuI-catalyzed tandem reaction of 2-bromobenzoates withcyclohexane-1,3-diones or acyclic 1,3-diones is developed. This strategy can also be extended to the one-pot synthesis of isoquinolin-1(2H)-one and 3,4-dihydrophenanthridine-1,6(2H,5H)-dione. A simple and convenient protocol for the synthesis of benzo[c]chromen-6-ones and 3-substituted isocoumarins through a CuI-catalyzed tandem reaction of 2-bromobenzoates with cyclohexane-1,3-dione or acyclic 1,3-dione has been developed. This strategy can also be extended to the one-pot synthesis of isoquionlin-1(2H)-one and 3,4-dihydrophenanthridine-1,6-(2H,5H)-dione. Copyright
- Fan, Xuesen,He, Yan,Cui, Liangyan,Guo, Shenghai,Wang, Jianji,Zhang, Xinying
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supporting information; experimental part
p. 673 - 677
(2012/03/10)
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- Synthesis and crystal structure of 4,7-diaryl-5-oxo-4H-benzo[b]pyran derivatives
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A green and convenient approach to the synthesis of a series of 4,7-diaryl-5-oxo-4H-benzo[b]pyran derivatives from appropriate aromatic aldehydes and 5-aryl-1,3-cyclohexanedione with malononitrile in the presence of dilute HCl as catalyst (30 mmol/L) is described. This method provides several advantages such as environmental friendliness, low cost, high yields, and simple work up procedure. The structures of all compounds were characterized by infrared (IR), mass spectrometry (MS), 1H NMR, and elemental analysis. The crystal structure of trans/cis-2-amino-3-cyano-7-(4'-methoxo- phenyl)-4-phenyl-5-oxo-4H-benzo[b]pyran, g, was determined by single crystal X-ray diffraction analysis. The crystal of compound g belongs to monoclinic with space group P 21/c, a = 8.477(3) nm, b = 18.948(6) nm, c = 24.915(7) nm, α = 90.00°, β = 107.388(11)°, γ= 90.00°, Z = 8, V = 3.819(2) nm3, R1 = 0.0754, wR2 = 0.2042.
- Cui, Bin,Chen, Li-Zhuang,Hu, Xiao-Lei,Wang, Ming,Han, Guang-Fan
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p. 900 - 904
(2012/10/29)
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- Consecutive Michael-claisen process for cyclohexane-1,3-dione derivative (CDD) synthesis from unsubstituted and substituted acetone 1
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A long-existing problem of cyclohexane-1,3-dione derivatives (CDD) synthesis from unreactive acetone through consecutive Michael-Claisen process was solved under this study. The practical applicability of this process was tested for a novel compound ethyl 3-(2,4-dioxocyclohexyl)propanoate for up to 20-gram scale. Furthermore, the scope of different acetone derivatives was investigated and resulted with similar consecutive Michael-Claisen process for CDD synthesis. The reaction exhibited remarkable regioselectivity in Michael addition followed by Claisen cyclization. In this process high substrate selectivity was observed for CDD synthesis following consecutive double-Michael-Claisen and Michael-Claisen cyclization. Georg Thieme Verlag Stuttgart · New York.
- Sharma, Dharminder,Shil, Arun K.,Singh, Bikram,Das, Pralay
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supporting information; experimental part
p. 1199 - 1204
(2012/06/15)
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- Synthesis of enaminones in aqueous media using catalytic dilute HCl
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(Chemical Equation Presented) A green and convenient approach to the synthesis of β-enaminones from aromatic amines and 5-substituted-1,3- cyclohexanedione in the presence of dilute hydrochloric acid (30 mmol=L) as a catalyst in solvent-free media is described. This method provides several advantages such as environmental friendliness, low cost, good yields, and simple workup procedure. Copyright Taylor & Francis Group, LLC.
- Cui, Bin,Wang, Rui-Hua,Chen, Li-Zhuang,Jin, Yan,Han, Guang-Fan
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scheme or table
p. 1064 - 1070
(2011/04/26)
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- Green synthesis and crystal structure of 4,7-diaryl-2-oxo(thio)-1,2,3,4,5, 6,7,8-octahydroquinazoline-5-one derivatives
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A green and convenient approach to the synthesis of novel 4,7-diaryl-2-oxo(thio)-1,2,3,4,5,6,7,8-octahydroquinazoline-5-one derivatives from appropriate aromatic aldehydes and 5-aryl-1,3-cyclohexanedione with urea or thiourea in the presence of dilute HCl as catalyst in water is described. This method provides several advantages such as environmental friendliness, low cost, high yields, and simple workup procedure. The structures of all compounds were characterized by elemental analysis, IR, MS, and 1H NMR. The crystal and molecular structure of 4-(4′-chlorophenyl)-7-(4′-methoxyphenyl)- 1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione 5m have been determined by single crystal X-ray diffraction analysis. The crystal of compound 5m belongs to monoclinic with space group P-21/c, a = 1.4353 (4) nm, b = 1.4011 (4) nm, c = 0.9248 (3) nm, α = 90.00°, β = 101.242 (6)°, γ = 90.00°, Z = 4, V = 1.8241 (9) nm3, R1 = 0.0448, and wR2 = 0.1022.
- Han, Guang-Fan,Cui, Bin,Chen, Li-Zhuang,Wang, Rui-Hua,Jin, Yan
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scheme or table
p. 312 - 316
(2011/06/10)
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- PROCESS FOR THE PRODUCTION OF OPTICALLY ACTIVE CYCLIC ENAMINONE DERIVATIVES
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A process for the production of optically active cyclic enaminone derivatives characterized by aminating one of the carbonyl groups of a cyclic 1,3-diketone derivative having a symmetry plane to obtain an optically isomeric mixture of chiral cyclic enamin
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- Synthesis and Antimalarial Properties of 1-Imino Derivatives of 7-Chloro-3-substituted-3,4-dihydro-1,9(2H,10H)-acridinediones and Related Structures
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To improve upon the activity and properties of the 3-aryl-7-chloro-3,4-dihydro-1,9(2H,10H)-acridinediones, a variety of 1-imino derivatives (3) were prepared and shown to be highly active antimalarial agents in both rodents and primates.Among structural modifications prepared, including N10-alkyl and C2-substituted analogs, removal of the C9 oxygen, and introduction of an imino side chain at C9, the imines of the N10-H acridinediones were the most active compounds obtained.The imino derivative of7-chloro-3-(2,4-dichlorophenyl)-3,4-dihydro-1,9(2H,10H)-acridinedione (9aa) proved to be highly active in advanced studies in primates.
- Kesten, Stephen J.,Degnan, Margaret J.,Hung, Jocelyn,McNamara, Dennis J.,Ortwine, Daniel F.,et al.
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p. 3429 - 3447
(2007/10/02)
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- CONDENSATION OF PHENOLS AND THEIR DERIVATIVES WITH AROMATIC COMPOUNDS IN THE PRESENCE OF ACIDIC AGENTS. VII. COMPARISON OF THE CONDENSATION OF PHENOLS WITH AROMATIC COMPOUNDS IN HF-SbF5 AND IN THE PRESENCE OF ALUMINUM HALIDES
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For the case of a series of phenols of the benzene and naphthalene series it was demonstrated that their condensation processes with benzene and its derivatives in the HF-SbF5 acid system and in the presence of aluminum halides are similar in nature.A possible explanation of the accumulated experimental data on the assumption that the diprotonated forms of the phenols and their ethers or 3, X = Cl, Br> the monoprotonated forms of the oxonium complexes with AlX3 take part in the condensation was considered.
- Repinskaya, I. B.,Barkhutova, D. D.,Makarova, Z. S.,Alekseeva, A. V.,Koptyug, V. A.
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p. 759 - 767
(2007/10/02)
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