- Desymmetrizing Isomerization of Alkene via Thiazolinyl Iminoquinoline Cobalt Catalysis
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We report a cobalt-catalyzed desymmetrizing isomerization of exo-cyclic alkenes to generate chiral 1-methylcyclohexene derivatives with good yields and enantioselectivities. A novel chiral thiazolinyl iminoquinoline ligand and its cobalt complex were desi
- Liu, Wenbo,Zheng, Yushan,Mao, Yihui,Chen, Jieping,Ren, Xiang,Cheng, Zhaoyang,Lu, Zhan
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p. 1158 - 1163
(2022/02/14)
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- The Silicon-Hydrogen Exchange Reaction: A Catalytic σ-Bond Metathesis Approach to the Enantioselective Synthesis of Enol Silanes
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The use of chiral enol silanes in fundamental transformations such as Mukaiyama aldol, Michael, and Mannich reactions as well as Saegusa-Ito dehydrogenations has enabled the chemical synthesis of enantiopure natural products and valuable pharmaceuticals. However, accessing these intermediates in high enantiopurity has generally required the use of either stoichiometric chiral precursors or stoichiometric chiral reagents. We now describe a catalytic approach in which strongly acidic and confined imidodiphosphorimidates (IDPi) catalyze highly enantioselective interconversions of ketones and enol silanes. These "silicon-hydrogen exchange reactions"enable access to enantiopure enol silanes via tautomerizing σ-bond metatheses, either in a deprotosilylative desymmetrization of ketones with allyl silanes as the silicon source or in a protodesilylative kinetic resolution of racemic enol silanes with a carboxylic acid as the silyl acceptor.
- Zhou, Hui,Bae, Han Yong,Leutzsch, Markus,Kennemur, Jennifer L.,Bécart, Diane,List, Benjamin
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p. 13695 - 13700
(2020/08/24)
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- Base-free oxidation of alcohols enabled by nickel(ii)-catalyzed transfer dehydrogenation
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An efficient nickel(ii)-catalyzed transfer dehydrogenation oxidation of alcohols is reported that relies on cyclohexanone as the formal oxidant and does not require the use of an external base. The synthetic utility of this protocol is demonstratedviathe facile oxidation of structurally complicated natural products.
- Ye, Danfeng,Liu, Zhiyuan,Sessler, Jonathan L.,Lei, Chuanhu
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supporting information
p. 11811 - 11814
(2020/10/13)
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- Enantioselective Synthesis of Chiral Oxime Ethers: Desymmetrization and Dynamic Kinetic Resolution of Substituted Cyclohexanones
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Axially chiral cyclohexylidene oxime ethers exhibit unique chirality because of the restricted rotation of C=N. The first catalytic enantioselective synthesis of novel axially chiral cyclohexylidene oximes has been developed by catalytic desymmetrization of 4-substituted cyclohexanones with O-arylhydroxylamines and is catalyzed by a chiral BINOL-derived strontium phosphate with excellent yields and good enantioselectivities. In addition, chiral BINOL-derived phosphoric acid catalyzed dynamic kinetic resolution of α-substituted cyclohexanones has been performed and yields versatile intermediates in high yields and enantioselectivities.
- Nimmagadda, Sri Krishna,Mallojjala, Sharath Chandra,Woztas, Lukasz,Wheeler, Steven E.,Antilla, Jon C.
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p. 2454 - 2458
(2017/02/23)
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- Method for synthesizing 4-(4-chlorphenyl) cyclohexanone
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The invention relates to the filed of organic synthesis, and discloses a method for synthesizing chemical intermediate 4-(4-chlorphenyl) cyclohexanone. The method includes the steps that (1) 4-(4-hydroxy-phenyl) cyclohexanone and pyridine are mixed in an
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Paragraph 0025; 0026; 0027; 0028
(2017/08/28)
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- Method for synthesizing 4-(4-chlorphenyl)cyclohexanone
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The invention relates to the field of organic synthesis and discloses a method for synthesizing a chemical intermediate 4-(4-chlorphenyl)cyclohexanone. The method includes the steps that firstly, 4-isopropenyl chlorobenzene is mixed with an organic solvent, N-bromo-succinimide is added for reaction for 1-6 h, solid is obtained, washed and dried after the reaction is completed, a compound 2 is obtained, a quenching reaction is carried out, extraction is conducted, an organic phase is obtained, and the compound 2 is obtained; secondly, the compound 2 and diethyl 1,3-acetonedicarboxylate are dissolved in alcohol, sodium alcoholate is added for reaction for 8-20 h, concentration is conducted after the reaction is completed, and a compound 3 is obtained; thirdly, the compound 3 is mixed with alcohol, an alkaline solution is added for a reflux reaction for 3-15 h, the product is adjusted to be alkalescent after the reaction is completed, and an organic phase is obtained, washed and dried after extraction. According to the synthesis method, raw materials are easy to obtain, reaction conditions are mild, selectivity is high, aftertreatment has good operability, the yield is high, production is easy to enlarge, and the method is more environmentally friendly.
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Paragraph 0028; 0029; 0030
(2017/08/27)
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- Optimization of TRPV6 calcium channel inhibitors using a 3D ligand-based virtual screening method
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Herein, we report the discovery of the first potent and selective inhibitor of TRPV6, a calcium channel overexpressed in breast and prostate cancer, and its use to test the effect of blocking TRPV6-mediated Ca2+-influx on cell growth. The inhib
- Simonin, Céline,Awale, Mahendra,Brand, Michael,Van Deursen, Ruud,Schwartz, Julian,Fine, Michael,Kovacs, Gergely,H?fliger, Pascal,Gyimesi, Gergely,Sithampari, Abilashan,Charles, Roch-Philippe,Hediger, Matthias A.,Reymond, Jean-Louis
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p. 14748 - 14752
(2016/02/05)
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- A novel process for synthesis of atovaquone
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A stereospecific efficient process for synthesis of atovaquone i.e. trans-2-[4-(4-chlorophenyl)cyclohexyl ]-3-hydroxy-1,4-naphthalenedione and its cis isomer from commercially available raw materials such as α-tetralone and 4-(4-chlorophenyl)cyclohexanone
- Roy, Bhairab N,Singh, Girij P,Lathi, Piyush S,Agrawal, Manoj K,Mitra, Rangan,Trivedi, Anurag
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p. 1299 - 1312
(2014/01/06)
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- IMPROVED SYNTHESIS OF 2-(4-(4-CHLOROPHENYL) CYCLOHEX-1-ENYL) -3, 4-DIHYDRONAPHTHALEN-1 (2H)-ONE; AN INTERMEDIATE FOR ATOVAQUONE
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A process for preparation of 2-(4-(4-chlorophenyl) cyclohex-l-enyl)-3,4-dihydronaphthalen- 1(2H)-one (V), key intermediate for synthesis of Atovaquone [I]. The process for preparation of compound(V) comprising of the steps of; i) Reaction of 2-(4-(4-chlorophenyl)-1-hydroxycyclohexyl)-3,4-dihydronaphthalen- 1(2H)-one (IV) with trifluro acetic anhydride in presence of base in organic solvent to yield compound of formula (XIa) ii) Elimination of trifluoroacetyl functionality of compound (XIa) in organic solvent and in presence of organic base to give compound of formula (V). The invention also provides a Process for preparation of compound(XIa) comprising of the steps of; i) reaction of 2-(4-(4-chlorophenyl)-l-hydroxy cyclohexyl)-3,4-dihydronaphthalen- 1(2H)-one (IV) with trifluro acetic anhydride in presence of organic base in organic solvent. A further process is provided for preparation of compound(V) from compound (XIa) comprising elimination reaction of trifluoroacetyl functionality compound (XIa) in organic solvent and in presence of organic base.
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Page/Page column 19
(2013/03/26)
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- Enantioselective baeyer-villiger oxidation: Desymmetrization of meso cyclic ketones and kinetic resolution of racemic 2-arylcyclohexanones
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Catalytic enantioselective Baeyer-Villiger (BV) oxidations of racemic and meso cyclic ketones were achieved in the presence of chiral N,N'-dioxide-Sc III complex catalysts. The BV oxidations of prochiral cyclohexanones and cyclobutanones afforded series of optically active μ- and γ-lactones, respectively, in up to 99% yield and 95% ee. Meanwhile, the kinetic resolution of racemic 2-arylcyclohexanones was also realized via an abnormal BV oxidation. Enantioenriched 3-aryloxepan-2-ones, whose formation is counter to the migratory aptitude, were obtained preferentially. Both the lactones and the unreacted ketones were obtained with high ee values.
- Zhou, Lin,Liu, Xiaohua,Ji, Jie,Zhang, Yuheng,Hu, Xiaolei,Lin, Lili,Feng, Xiaoming
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p. 17023 - 17026,4
(2012/12/12)
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- Enantioselective baeyer-villiger oxidation: Desymmetrization of meso cyclic ketones and kinetic resolution of racemic 2-arylcyclohexanones
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Catalytic enantioselective Baeyer-Villiger (BV) oxidations of racemic and meso cyclic ketones were achieved in the presence of chiral N,N'-dioxide-Sc III complex catalysts. The BV oxidations of prochiral cyclohexanones and cyclobutanones afforded series of optically active μ- and γ-lactones, respectively, in up to 99% yield and 95% ee. Meanwhile, the kinetic resolution of racemic 2-arylcyclohexanones was also realized via an abnormal BV oxidation. Enantioenriched 3-aryloxepan-2-ones, whose formation is counter to the migratory aptitude, were obtained preferentially. Both the lactones and the unreacted ketones were obtained with high ee values.
- Zhou, Lin,Liu, Xiaohua,Ji, Jie,Zhang, Yuheng,Hu, Xiaolei,Lin, Lili,Feng, Xiaoming
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p. 17023 - 17026
(2013/01/15)
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- NOVEL METHOD FOR PREPARATION OF ATOVAQUONE
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Provided is a process of preparation of 2-[trans,-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy- 1,4-naphthoquinone, i.e. Atovaquone [I] which is cost effective, green, and eco-friendly process, without separation of any diastereomers or geometric isomers of intermediates obtained during the reactions. Also provided is separation of 'cis' and 'trans ' isomer of intermediates VI, VII and VIII through selective crystallization in an appropriate solvent. A method for converting 2-[cis,-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthoquinone to 2-[trans-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-l,4-naphthoquinone in presence of Lewis/ Bronsted acid is also provided. A process for preparation of compound 2-(4-(4- chlorophenyl)- 1 -hydroxy cyclohexyl)-3,4-dihydronaphthalen- 1 (2H)-one [IV] comprising condensation of (1,2-dihydronaphthalen-4-yloxy)trimethylsilane [II] with 4-(4- chlorophenyl)cyclohexanone [III] in presence of Lewis acid in organic solvent. The invention also encompasses a highly efficient and atomeconomic process for synthesis of compound [III] i.e. 4-(4-chlorophenyl)cyclohexanone as well as a process for synthesis of 2-[cis-4-(4'- chlorophenyl)cyclohexyl]-3-hydroxy-l,4-naphthoquinone. Further provided is a process for isomerization of cis- Atovaquone i.e. 2-[cis-4-(4'-chlorophenyl)cyclohexyl]-3-hydroxy-l,4- naphthoquinone to tnms-Atovaquone i.e. 2-[trans-4-(4'-chlorophenyl)cyclohexyl]-3- hydroxy- 1,4-naphthoquinone in presence of Lewis acid.
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- Aryl extensions of thienopyrimidinones as fibroblast growth factor receptor 1 kinase inhibitors
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Optimization of thienopyrimidinone derivatives as FGFR1 kinase inhibitors is being pursued. The present results confirm predictions of computational modeling that an aryl substituent can be introduced at the 2-position in structure 3. The substituent is anticipated to project deeper into the binding site and provide opportunities for enhanced activity and selectivity. The most potent analog reported herein, 13, has a 4-hydroxyphenyl substituent and yields an IC50 of 6 μM for inhibition of phosphorylation by FGFR1 kinase. It was also found that the western anisole-containing substituent in 3 can be replaced by a propionic acid group with no loss in potency and with potentially significant gains in pharmacologically relevant properties.
- Ekkati, Anil R.,Mandiyan, Valsan,Ravindranathan, Krishna P.,Bae, Jae H.,Schlessinger, Joseph,Jorgensen, William L.
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scheme or table
p. 2228 - 2231
(2011/05/05)
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- Discovery of 1-amino-4-phenylcyclohexane-1-carboxylic acid and its influence on agonist selectivity between human melanocortin-4 and -1 receptors in linear pentapeptides
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Linear pentapeptides (Penta-cis-Apc-DPhe-Arg-Trp-Gly-NH2) containing 1-amino-4-phenylcyclohexane-1-carboxylic acid (cis-Apc) and substituted Apc are potent hMC4R agonists and they are inactive or weakly active in hMC1R, hMC3R, and hMC5R agonist assays. This study, together with our earlier report on 5-BrAtc, demonstrated the importance of replacing His 6 with phenyl-containing rigid templates in achieving good hMC4R agonist potency and selectivity against hMC1R in linear pentapeptides.
- Chu, Xin-Jie,Bartkovitz, David,Danho, Waleed,Swistok, Joseph,Cheung, Adrian Wai-Hing,Kurylko, Grazyna,Rowan, Karen,Yeon, Mitch,Franco, Lucia,Qi, Lida,Chen, Li,Yagaloff, Keith
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p. 4910 - 4914
(2007/10/03)
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- GUANIDINE DERIVATIVES AND USE THEREOF AS NEUROPEPTIDE FF RECEPTOR ANTAGONISTS
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The invention relates to guanidine derivatives of formula (I) where: A = a chain of 3-c6 carbon atoms, one of which can be replaced by -N(R')- or -O- and R' = H or a substituent, where the ring skeleton only contains both double bonds of the thiazole component, the pharmaceutically-acceptable acid addition salts of basic compounds of formula (I), the pharmaceutically-acceptable salts of compounds of formula (I),, comprising acid groups, with bases, the pharmaceutically-acceptable esters of hydroxy or carboxyl group containing compounds of formula (I) and the solvates or hydrates thereof, which are partly known and partly novel and exhibit a neuropeptide FF receptor antagonist effect. The above are suitable for the treatment of pain and hyperalgesia, withdrawal symptoms in alcohol, psychotropic and nicotine dependencies, for improvement or cure of said dependencies, for regulation of insulin excretion, food intake, memory functions, blood pressure, electrolyte and energy management and for treatment of urinary incontinence. The above can be produced using generally used methods and processed to give medicaments.
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- Selective cyclic peptides with melanocortin-4 receptor (MC4-R) agonist activity
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Peptides cyclized via disulfide or lactam bridges having melanocortin-4 receptor (MC4-R) agonist activity useful for treatment of obesity.
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- Synthesis of atovaquone
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A short synthesis of atovaquone I is achieved via the radical coupling of the trans-1,4-substituted cyclohexyl mono-oxalate 2 and 2- chloronapthoquinone under phase transfer conditions.
- Williams, David R.,Clark, Michael P.
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p. 7629 - 7632
(2007/10/03)
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