- Catalytic Asymmetric Construction of Tertiary Carbon Centers Featuring an α-Difluoromethyl Group with CF2H-CH2-NH2as the "building Block"
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We report here for the first time a novel difluoromethylated ketimine building block condensed by thioisatin and difluoroethylamine, offering efficient access to a broad range of enantioenriched products bearing difluoroethylamine units (27 examples, ≤98% yield, >99% ee) in the presence of quinine-derived squaramide. Further transformation of the intermediate would generate a variety of versatile functional blocks like α-difluoromethyl amines, β-amino acid, and β-diamine with retention of the enantiomeric excess at the difluoromethyl-bound carbon.
- Gao, Fengyun,Guo, Yifei,Sun, Mengmeng,Wang, Yalan,Yang, Changyan,Wang, Yuqiang,Wang, Kairong,Yan, Wenjin
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supporting information
p. 2584 - 2589
(2021/04/13)
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- Chlorination of Conjugated Nitroalkenes with PhICl 2and so 2Cl 2for the Synthesis of α-Chloronitroalkenes
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Chlorination of conjugated nitroalkenes with iodobenzene dichloride or sulfuryl chloride to give target α-chloronitroalkenes in good yields is described. Details of the procedure depend on the donating ability of the nitroalkene substituents. The activity of the described chlorinating agents increases in order 'PhICl 2/Py' 2Cl 2' 2Cl 2/HCl' with the former producing the best yields for highly donating substrates and the latter for non-activated groups. An autocatalytic role of hydrogen chloride and the chemoselectivity of chlorination were also demonstrated.
- Fadeeva, Anastasia A.,Ioffe, Sema L.,Tabolin, Andrey A.
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supporting information
p. 2679 - 2688
(2020/11/02)
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- Synthesis, antiproliferative and pro-apoptotic effects of nitrostyrenes and related compounds in Burkitt’s lymphoma
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Background: Cancers of the lymphatic cells (lymphomas) account for approximately 12% of malignant diseases worldwide. The nitrostyrene scaffold is identified as a lead target structure for the development of particularly effective compounds targeting Burkitt’s lymphoma (BL). Objectives: The aims of the curent study were to synthesise a panel of nitrostyrene compounds and to evaluate their activity in Burkitt’s lymphoma (BL). Methods: A panel of structurally varied compounds were designed and synthesised using Henry Knoevenagel condensation reactions. Single crystal X-Ray analysis confirmed the E configuration for six examples of these novel structures. A number of nitrostyrene-related compounds were also investigated including 1,3-bis(aryl)-2-nitropropenes together with heterocyclic scaffolds containing the nitrovinyl pharmacophore such as 3-nitro-2-phenyl-2H-chromenes. The antiproliferative activities of the compounds were evaluated using the BL cell lines EBV- MUTU-1 and EBV+ DG-75 (chemoresistant) to establish preliminary structure-activity relationships. Results: Lead compounds with optimized nitrostyrene scaffolds and 3-nitro-2-phenyl-2Hchromene structures were successfully established with typical IC50 values of 0.45 μM and 0.47 μM in MUTU-1 cells and 1.41 μM and 1.92 μM, respectively, in DG-75 cells. The mechanism of cell death was identified as apoptotic and the lead compound was found to elicit comparable apoptotic effects to Taxol in Burkitt’s lymphoma cell lines MUTU-1 and DG-75. Conclusion: This class of pharmaceutically active compounds with potential for the treatment of Burkitt’s lymphoma suggest a potential role for nitrostyrene based agents in chemotherapy.
- Byrne, Andrew J.,Bright, Sandra A.,Fayne, Darren,McKeown, James P.,McCabe, Thomas,Twamley, Brendan,Williams, Clive,Meegan, Mary J.
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p. 181 - 199
(2018/03/13)
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- A Bioinspired Synthesis of Polyfunctional Indoles
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Polyfunctional indoles bearing substituents at C5 and C6 are prevalent in natural products, pharmaceuticals, agrochemicals, and materials. Owing to the remoteness of the C5 and C6 positions, indoles of this family can be difficult to prepare, and often require multistep syntheses. Herein, we describe a concise process that converts simple derivatives of tyrosine into 5,6-difunctionalized indoles by direct oxidation of C?H, N?H, and O?H bonds. Our work draws inspiration from the biosynthetic polymerization of tyrosine to make melanin pigments, but makes an important departure to provide well-defined indole heterocycles.
- Huang, Zheng,Kwon, Ohhyeon,Huang, Haiyan,Fadli, Aziz,Marat, Xavier,Moreau, Magali,Lumb, Jean-Philip
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supporting information
p. 11963 - 11967
(2018/09/11)
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- Synthesis and biological evaluation of novel inhibitors against 1,3,8-trihydroxynaphthalene reductase from Magnaporthe grisea
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1,3,8-Trihydroxynaphthalene reductase (3HNR) is an essential enzymes that is involved in fungal melanin biosynthesis. Based on the structural informations of active site of 3HNR, a series of β-nitrostyrene compounds were rationally designed and synthesized. The enzymatic activities of these compounds showed that most of them exhibited high inhibitory activities (50 = 0.29 μM). In particular, some of these compounds had moderate fungicidal activity against Magnaporthe grisea. Compound 3-4 showed high in vivo activities against M. grisea (EC50 = 9.5 ppm). Furthermore, compound 3-2 was selected as a representative molecule, and the probable binding mode of this compound and the surrounding residues in the active site of 3HNR was elucidated by using molecular dock. The positive results suggest that β-nitrostyrene derivatives are most likely to be promising leads toward the discovery of novel agent of rice blast.
- Chen, Haifeng,Han, Xinya,Qin, Nian,Wei, Lin,Yang, Yue,Rao, Li,Chi, Bo,Feng, Lingling,Ren, Yanliang,Wan, Jian
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p. 1225 - 1230
(2016/03/01)
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- Dihydrooxazine N-Oxide Intermediates as Resting States in Organocatalytic Kinetic Resolution of Functionalized Nitroallylic Amines with Aldehydes
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Kinetic resolution of nitroallylic amines was established using chiral α,α-l-diphenylprolinol silyl ether auxiliary through isolation of the dihydrooxazine N-oxide intermediates. Further hydrolyzing the resting states provided tetrahydropyridines in high chemical yields and high to excellent stereoselectivities (up to >20:1 dr and 98% ee). A detailed mechanistic explanation for stereoselective protonation in the dihydrooxazine was probed computationally. In addition, the probable intermediates in α-halogenation of aldehydes (masked with enamines) were isolated to provide crystallographic evidence.
- Gurubrahamam, Ramani,Chen, Yan Ming,Huang, Wan-Yun,Chan, Yu-Te,Chang, Hsiang-Kai,Tsai, Ming-Kang,Chen, Kwunmin
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supporting information
p. 3046 - 3049
(2016/07/13)
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- Diaminosilane-functionalized on silicate-stabilised hydrotalcite (MA-HTSi-DA): As potential catalyst for nitro-aldol condensation
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Diaminosilane was introduced into silicate-anion-intercalated hydrotalcite (HT-Si) using a post-synthesis method. The resulting functionalized materials possess surface basicity. The textural properties of the functionalized materials were systematically investigated through powder XRD, FTIR and MAS-NMR studies. The diamine-functionalized materials showed very good catalytic activity for the nitro-aldol condensation of benzaldehyde and nitromethane under solvent-free conditions. The materials showed comparable catalytic activity upon recycling.
- Thangaraj, Baskaran,Jayaraj, Christopher,Srinivasan, Radhakrishnan,Ayyamperumal, Sakthivel
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- Synthesis of substituted nitroolefins: A copper catalyzed nitrodecarboxylation of unsaturated carboxylic acids
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A novel, mild and convenient method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their nitroolefins is achieved using a catalytic amount of CuCl (10 mol%) and tert-butyl nitrite (2 equiv.) as a nitrating agent in the presence of air. This reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives, which are generally difficult to access from other conventional methods. Additionally, this reaction is selective as the E-isomer of the acid derivatives furnishes the corresponding E-nitroolefins. One more salient feature of the method is, unlike other methods, no metal nitrates or HNO3 are employed for the transformation.
- Rokade, Balaji V.,Prabhu, Kandikere Ramaiah
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p. 6713 - 6716
(2013/10/01)
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- Ethylenediamine: A highly effective catalyst for one-pot synthesis of aryl nitroalkenes via henry reaction and dehydration
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Ethylenediamine (H2NCH2CH2NH2) was found to be a highly effective catalyst for the condensation of aryl aldehydes with nitromethane (or nitroethane). When 1%-2% (mol%) of ethylenediamine was used as the catalyst, the one-pot reaction of aryl aldehydes with nitromethane (or nitroethane) by refluxing for 3-10 h efficiently afforded various arylnitroalkenes 1a-1y in 85%-97% yields. Ethylenediamine (H 2NCH2CH2NH2) was found to be a highly effective catalyst for the condensation of aryl aldehydes with nitromethane (or nitroethane). When 1-2 mol% of ethylenediamine was used as the catalyst, the one-pot reaction of aryl aldehydes with nitromethane (or nitroethane) by refluxing for 3-10 h efficiently afforded various aryl nitroalkenes 1a-1y in 85%-97% yields. Copyright
- Yang, Jianxin,Dong, Jing,Lue, Xia,Zhang, Qiang,Ding, Wei,Shi, Xiaoxin
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p. 2827 - 2833
(2013/08/23)
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- S1P RECEPTORS MODULATORS
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The invention relates to novel compounds that have S1P receptor modulating activity and, preferably, apoptotic activity and/or anti proliferative activity against cancer cells and other cell types. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, cancer. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as cancer.
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Page/Page column 98
(2010/04/30)
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- PYRIDINE DERIVATIVE CONTAINING ((PHOSPHONOOXY)METHYL)PYRIDINIUM RING, AND ANTIFUNGAL AGENT CONTAINING THESE DERIVATIVE
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The present invention provides an antifungal agent that has excellent antifungal action, and is also superior in terms of its properties, and particularly its solubility in water and safety in an aqueous solution, and its in vivo pharmacokinetics and safety. According to the present invention, there is provided a compound represented by the following formula (I), or a salt thereof: wherein R1 represents a hydrogen atom, a halogen atom, an amino group, a C1-6 alkyl group, a C1-6 alkoxy group, or a C1-6 alkoxy C1-6 alkyl group; R2 represents a hydrogen atom, a C1-6 alkyl group, an amino group, or a di-C1-6 alkylamino group;R3 represents a hydrogen atom, a halogen atom, or a C1-6 alkyl group; andR4 represents a hydrogen atom, a halogen atom, or a C1-6 alkyl group.
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Page/Page column 8-9
(2011/01/05)
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- The total synthesis of cannabisin G
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A convenient method for the synthesis of lignanamide cannabisin G, starting from vanillin, was developed. The convergent synthesis was based on the Stobbe reaction as C-C bond-forming steps to give the skeleton of lignan, which was condensed with a deriva
- Yamu, Xia,Yinglan, Guo,Yanling, Wen
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p. 1617 - 1623
(2011/09/20)
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- 2-Arylthiomorpholine derivatives as potent and selective monoamine oxidase B inhibitors
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2-Arylthiomorpholine and 2-arylthiomorpholin-5-one derivatives, designed as rigid and/or non-basic phenylethylamine analogues, were evaluated as rat and human monoamine oxidase inhibitors. Molecular docking provided insight into the binding mode of these inhibitors and rationalized their different potencies. Making the phenylethylamine scaffold rigid by fixing the amine chain in an extended six-membered ring conformation increased MAO-B (but not MAO-A) inhibitory activity relative to the more flexible α-methylated derivative. The presence of a basic nitrogen atom is not a prerequisite in either MAO-A or MAO-B. The best Ki values were in the 10-8 M range, with selectivities towards human MAO-B exceeding 2000-fold.
- Lühr, Susan,Vilches-Herrera, Marcelo,Fierro, Angélica,Ramsay, Rona R.,Edmondson, Dale E.,Reyes-Parada, Miguel,Cassels, Bruce K.,Iturriaga-Vásquez, Patricio
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experimental part
p. 1388 - 1395
(2010/05/17)
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- PYRIDINE DERIVATIVES SUBSTITUTED BY HETEROCYCLIC RING AND PHOSPHONOAMINO GROUP, AND ANTI-FUNGAL AGENT CONTAINING SAME
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Anti-fungal agent having excellent anti-fungal action physicochemical properties including safety and water solubility. Compound represented by formula (I), or salt thereof: wherein R1 represents hydrogen, halogen, amino, R11-NH- wherein R11 represents C1-6 alkyl, hydroxy C1-6 alkyl, C1-6 alkoxy C1-6 alkyl, or C1-6alkoxycarbonyl C1-6 alkyl, R12-(CO)-NH- wherein R12 represents C1-6 alkyl group or C1-6 alkoxy C1-6 alkyl, C1-6 alkyl, hydroxy C1-6 alkyl, cyano C1-6 alkyl, C1-6 alkoxy, or C1-6 alkoxy C1-6 alkyl or a phosphonoamino group; R2 represents hydrogen, C1-6 alkyl, amino, or a di C1-6 alkylamino group or a phosphonoamino group; one of X and Y is nitrogen while the other is nitrogen or oxygen; ring A represents a 5- or 6-member heteroaryl ring or a benzene ring which may have a halogen atom or 1 or 2 C1-6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, oxygen, sulfur, -CH2O-, -OCH2-, -NH-, -CH2NH-, -NHCH2-, -CH2S-, or -SCH2-; R3 represents hydrogen or halogen or C1-6 alkyl, C3-8 cycloalkyl, C6-10 aryl, a 5- or 6-member heteroaryl group or a 5- or 6-member nonaromatic heterocyclic group which may have 1 or 2 substituents; and R4 represents hydrogen or halogen; provided that either R1 or R2 represents a phosphonoamino group.
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Page/Page column 50
(2009/04/24)
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- Heterocycles substituted pyridine derivatives and antifungal agent containing thereof
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An object of the present invention is to provide an antifungal agent which has excellent antifungal effects and is superior in terms of its physical properties, safety and metabolic stability. According to the present invention, there is disclosed a compound represented by the following formula (I), or a salt thereof: wherein R1 represents a hydrogen atom, a halogen atom, an amino group, a C1-6 alkyl group, a C1-6 alkoxy group or a C1-6 alkoxy C1-6 alkyl group; R2 represents a hydrogen atom, a C1-6 alkyl group, an amino group or a di C1-6 alkylamino group; one of X and Y is a nitrogen atom while the other is a nitrogen atom or an oxygen atom; ring A represents a 5- or 6-member heteroaryl ring or a benzene ring which may have a halogen atom, or 1 or 2 C1-6 alkyl groups; Z represents a single bond, a methylene group, an ethylene group, an oxygen atom, a sulfur atom, —CH2O—, —OCH2—, —NH—, —CH2NH—, —NHCH2—, —CH2S—, or —SCH2—; R3 represents a hydrogen atom, a halogen atom, a C1-6 alkyl group, a C3-8 cycloalkyl group, a C6-10 aryl group, a 5- or 6-member heteroaryl group, or 5- or 6-member non-aromatic heterocyclic group which may have 1 or 2 substituents; and R4 represents a hydrogen atom or a halogen atom.
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Page/Page column 52
(2010/11/27)
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- Structure-based approach to falcipain-2 inhibitors: Synthesis and biological evaluation of 1,6,7-Trisubstituted dihydroisoquinolines and isoquinolines
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1,4,7-Trisubstituted isoquinolines were designed, synthesized and evaluated for their inhibition against Plasmodium falciparum cysteine protease falcipain-2. The 1-benzyloxyphenyl-dihydroisoquinoline and -isoquinoline derivatives were found to exhibit better activity against falcipain-2 than their corresponding 1-hydroxyphenyl or 1-methoxyphenyl analogues. The docking scores correlate with the IC50 values of compounds and give a high coefficient correlation of 0.94.
- Batra, Sanjay,Sabnis, Yogesh A.,Rosenthal, Philip J.,Avery, Mitchell A.
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p. 2293 - 2299
(2007/10/03)
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- Cephalosporin derivatives
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A compound of the formula I: STR1 in which R1 is any C-3 substituent from antibacterially-active cephalosporins; R2 is any C-4 substituent from antibacterially-active cephalosporins; R3 is H, hydroxy, amino, 1-6C alkyl, 1-
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- Diazaestrones and analogs. I. Pharmacological study and synthesis of heterosteroid analogs to establish structure-analgesic activity relationships
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With the intention of showing the effect, about pharmacological properties, in replacing two estron asymetric carbon by nitrogen atoms and removal of angular methyl from steroid, stereospecific synthesis of 8,13-diazaestron and several substituted similar compounds was realized from β-1-(succinimidoethyl)-dihydroisoquinolines, precursors of a C open ring synthesis. The splitting of the 2-methoxydiazaestron methyl ester was carried out by mean of binaphthylphosphoric acid, and synthesis of several modified analogs of heterosteroid, was carried out to determine the effect of aromatic ring reduction, lactamic carbonyl reduction, and distance between 8 and 13 nitrogen atoms, about pharmacological activity. Hormonal, spasmolytic and analgesic activities were studied, good results were observed in analgesic activity.
- Hocquaux,Marcot,Redeuilh,et al.
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p. 319 - 329
(2007/10/02)
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