- Asymmetric Hydroacylation Involving Alkene Isomerization for the Construction of C3-Chirogenic Center
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A new transformation pattern for enantioselective intramolecular hydroacylation has been developed involving an alkene isomerization strategy. Proceeding through a five-membered rhodacycle intermediate, 3-enals were converted to C3- or C3,C5-chirogenic cyclopentanones with satisfactory yields, diastereoselectivities, and enantioselectivities. A catalytic cycle has been theoretically calculated and the origin of the stereoselection is rationally explained.
- Liu, Chong,Yuan, Jing,Zhang, Zhenfeng,Gridnev, Ilya D.,Zhang, Wanbin
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supporting information
p. 8997 - 9002
(2021/03/16)
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- Synthesis and Structure-Activity Relationship of Dual-Stage Antimalarial Pyrazolo[3,4- b]pyridines
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Malaria remains one of the most deadly infectious diseases, causing hundreds of thousands of deaths each year, primarily in young children and pregnant mothers. Here, we report the discovery and derivatization of a series of pyrazolo[3,4-b]pyridines targeting Plasmodium falciparum, the deadliest species of the malaria parasite. Hit compounds in this series display sub-micromolar in vitro activity against the intraerythrocytic stage of the parasite as well as little to no toxicity against the human fibroblast BJ and liver HepG2 cell lines. In addition, our hit compounds show good activity against the liver stage of the parasite but little activity against the gametocyte stage. Parasitological profiles, including rate of killing, docking, and molecular dynamics studies, suggest that our compounds may target the Qo binding site of cytochrome bc1.
- Eagon, Scott,Hammill, Jared T.,Sigal, Martina,Ahn, Kevin J.,Tryhorn, Julia E.,Koch, Grant,Belanger, Briana,Chaplan, Cory A.,Loop, Lauren,Kashtanova, Anna S.,Yniguez, Kenya,Lazaro, Horacio,Wilkinson, Steven P.,Rice, Amy L.,Falade, Mofolusho O.,Takahashi, Rei,Kim, Katie,Cheung, Ashley,Dibernardo, Celine,Kimball, Joshua J.,Winzeler, Elizabeth A.,Eribez, Korina,Mittal, Nimisha,Gamo, Francisco-Javier,Crespo, Benigno,Churchyard, Alisje,García-Barbazán, Irene,Baum, Jake,Anderson, Marc O.,Laleu, Beno?t,Guy, R. Kiplin
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p. 11902 - 11919
(2020/11/26)
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- Catalytic Activation of 1-Cyano-3,3-dimethyl-3-(1H)-1,2-benziodoxole with B(C6F5)3 Enabling the Electrophilic Cyanation of Silyl Enol Ethers
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The Lewis acidic activation of a hypervalent iodine reagent containing a transferable cyano group, 1-cyano-3,3-dimethyl-3-(1H)-1,2-benziodoxole (CDBX), with B(C6F5)3, to achieve the catalytic electrophilic cyanation of silyl enol ethers is presented. Mechanistic studies indicate that CDBX is activated through coordination of its cyano group to B(C6F5)3, thus enabling the electrophilic cyanation reaction to occur.
- Nagata, Takaya,Matsubara, Hiroki,Kiyokawa, Kensuke,Minakata, Satoshi
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supporting information
p. 4672 - 4675
(2017/09/12)
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- One-pot dichlorinative deamidation of primary β-ketoamides
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An approach to the dichlorinative deamidation of primary β-ketoamides through ketonic cleavage is described, and a series of α,α-dichloroketones were furnished mostly in the presence of TEMPO. Based on control experiments, a mechanism involving tandem dichlorination and deamidation is proposed to interpret the observed reactivity.
- Zheng, Congke,Zhang, Xiaohui,Ijaz Hussain, Muhammad,Huang, Mingming,Liu, Qing,Xiong, Yan,Zhu, Xiangming
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supporting information
p. 574 - 577
(2017/01/16)
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- Palladium-Catalyzed Carbonylative α-Arylation of tert -Butyl Cyanoacetate with (Hetero)aryl Bromides
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A three-component coupling protocol has been developed for the generation of 3-oxo-3-(hetero)arylpropanenitriles via a carbonylative palladium-catalyzed α-arylation of tert-butyl 2-cyanoacetates with (hetero)aryl bromides followed by an acid-mediated decarboxylation step. Through the combination of only a stoichiometric loading of carbon monoxide and mild basic reaction conditions such as MgCl2 and dicyclohexylmethylamine for the deprotonation step, an excellent functional group tolerance was ensured for the methodology. Through the use of 13C-labeled carbon monoxide generated from 13COgen, the corresponding 13C-isotopically labeled β-ketonitriles were obtained, and these products could subsequently be converted into cyanoalkynes and 3-cyanobenzofurans with site specific 13C-isotope labeling. (Chemical Equation Presented).
- Jensen, Mikkel T.,Juhl, Martin,Nielsen, Dennis U.,Jacobsen, Mikkel F.,Lindhardt, Anders T.,Skrydstrup, Troels
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p. 1358 - 1366
(2016/03/01)
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- Umpolung Strategy for Synthesis of β-Ketonitriles through Hypervalent Iodine-Promoted Cyanation of Silyl Enol Ethers
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An efficient method to synthesize β-ketonitriles from silyl enol ethers by an umploung hypervalent iodine(III)-CN species generated in situ from PhIO/BF3·Et2O/TMSCN has been developed for the first time. This method can be applied to structurally diverse aromatic and aliphatic substrates and further extended to preparation of bioactive compounds like 5-aminopyrazole and 5-aminoisoxazole.
- Shen, Hang,Li, Jiaqiang,Liu, Qing,Pan, Jing,Huang, Ruofeng,Xiong, Yan
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p. 7212 - 7218
(2015/07/28)
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- Specific 1,2-Hydride Shift in the Boron Trifluoride Catalyzed Reactions of Aromatic Aldehydes with Diazoacetonitrile: Simple Synthesis of β-Ketonitriles
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A series of β-ketonitriles was synthesized within 30 min under mild conditions through the BF3 ·OEt2-catalyzed addition reactions of diazoacetonitrile to aromatic aldehydes and subsequent 1,2-hydride shift. This method is advantageous in that it is operationally simple, mild and metal-free conditions are used, the substrate scope is wide, and the products are obtained in moderate to high yields (up to 81 %). Additionally, γ,δ-unsaturated β-ketonitriles are also accessible by this method by using cinnamaldehydes.
- Yang, Zhanhui,Son, Kwon-Il,Li, Siqi,Zhou, Bingnan,Xu, Jiaxi
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supporting information
p. 6380 - 6384
(2016/02/18)
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- Cascade synthesis of 3-aza-bicyclo[3.1.0]hex-2-ene derivatives from N-allyl enamines
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An efficient iodine-mediated cascade synthesis of 3-aza-bicyclo[3.1.0]hex-2-ene derivatives from easily prepared N-allyl enamines has been developed. The advantages of the reaction include facilitative preparation of substrates 3a-t, good functional group tolerance and transition-metal-free conditions.
- Zhai, Sheng-Xian,Dong, Hong-Ru,Chen, Zi-Bao,Hu, Yi-Ming,Dong, Heng-Shan
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p. 8405 - 8412
(2015/03/04)
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- Copper-catalyzed Aerobic Oxidative coupling of Aromatic Alcohols and Acetonitrile to β-Ketonitriles
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A practical, convenient, and cheap coppercatalyzed aerobic oxidative coupling of aromatic alcohols and acetonitrile to β-ketonitriles has been developed. The green C-C bond formation involving the loss of two hydrogen atoms from the corresponding two carbons, respectively, unlocks opportunities for markedly different synthetic strategies.
- Shen, Jiaxuan,Yang, Dejun,Liu, Yuxiao,Qin, Shuangshuang,Zhang, Jingwu,Sun, Jiangkai,Liu, Chunhui,Liu, Chaoyang,Zhao, Xiaomei,Chu, Changhu,Liu, Renhua
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supporting information
p. 350 - 353
(2014/04/03)
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- Palladium-catalyzed carbonylation with Mo(CO)for the synthesis of benzoylacetonitriles
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Benzoylacetonitriles were synthesized by the palladium-catalyzed carbonylation of aryl iodides and trimethylsilylacetonitrile using Mo(CO)as a carbon monoxide source. Pd(PPhCland CuFwere employed as the catalyst and activator, respectively. A variety of aryl iodides bearing alkyl, alkoxy, fluoro, chloro, bromo, nitrile, ester, and ketone groups afforded the corresponding benzoylacetonitriles in moderate to good yields. Georg Thieme Verlag Stuttgart ? New York.
- Pyo, Ayoung,Park, Ahbyeol,Jung, Hyunmin,Lee, Sunwoo
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supporting information
p. 2885 - 2888
(2012/10/29)
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- Synthesis of benzoylacetonitriles from Pd-catalyzed carbonylation of aryl iodides and trimethylsilylacetonitrile
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Palladium-catalyzed carbonylation of aryl iodides and trimethylsilylacetonitrile to produce benzoylacetonitrile derivatives through a one-pot, three-component reaction is described. This preparation method provides good yields of the carbonylated products without any additional ligands. It has a broad substrate scope with a high tolerance for a variety of functional groups.
- Park, Ahbyeol,Lee, Sunwoo
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supporting information; experimental part
p. 1118 - 1121
(2012/03/27)
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- Synthesis and biological evaluation of 3-aryl-quinoxaline-2- carbonitrile 1,4-Di-N-oxide derivatives as hypoxic selective anti-tumor agents
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A series of 3-aryl-2-quinoxaline-carbonitrile 1,4-di-N-oxide derivatives were designed, synthesized and evaluated for hypoxic and normoxic cytotoxic activity against human SMMC-7721, K562, KB, A549 and PC-3 cell lines. Many of these new compounds displayed more potent hypoxic cytotoxic activity compared with TX-402 and TPZ in the tumor cells based evaluation, which confirmed our hypothesis that the replacement of the 3-amine with the substituted aryl ring of TX-402 increases the hypoxic anti-tumor activity. The preliminary SAR revealed that 3-chloro was a favorable substituent in the phenyl ring for hypoxic cytotoxicity and 7-methyl or 7-methoxy substituted derivatives exhibited better hypoxic selectivity against most of the tested cell lines. The most potent compound, 7-methyl-3-(3-chlorophenyl)-quinoxaline-2-carbonitrile 1,4-dioxide (9h) was selected for further anti-tumor evaluation and mechanistic study. It also exhibited significant cytotoxic activity against BEL-7402, HepG2, HL-60, NCI-H460, HCT-116 and CHP126 cell lines in hypoxia with IC50 values ranging from 0.31 to 3.16 μM, and preliminary mechanism study revealed that 9h induced apoptosis in a caspase-dependent pathway.
- Hu, Yunzhen,Xia, Qing,Shangguan, Shihao,Liu, Xiaowen,Hu, Yongzhou,Sheng, Rong
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p. 9683 - 9696
(2012/11/13)
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- 3-Substituted-(5-arylfuran-2-ylcarbonyl)guanidines as NHE-1 inhibitors
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The C-3 substituents effect on NHE-1 inhibitory activity of (5-arylfuran-2-ylcarbonyl)guanidines, previously identified as potent NHE-1 inhibitors, was investigated. The introduction of amine or alkyl groups at the 3-position of the furan ring, next to the acylguanidine moiety, remarkably improves NHE-1 inhibitory potency. Especially the important finding is that 5-(2,5-dichloro)phenyl and 5-(2-methoxy-5-chloro)phenyl derivatives exhibit high NHE-1 inhibitory activities (IC50 0.02 μM) that match those of 3-unsubstituted derivatives.
- Lee, Sunkyung,Kim, Taemi,Lee, Byung Ho,Yoo, Sung-eun,Lee, Kyunghee,Yi, Kyu Yang
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p. 1291 - 1295
(2008/02/02)
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- Novel potent neuropeptide Y Y5 receptor antagonists: Synthesis and structure-activity relationships of phenylpiperazine derivatives
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A series of phenylpiperazine derivatives were synthesized and evaluated for their neuropeptide Y (NPY) Y5 receptor antagonistic activities. The benzindane portion of 2 was replaced by 1-phenylpiperazine, resulting in novel urea derivative 3f. Subsequent optimization of the phenylpiperazine template by substitution of the phenyl moiety resulted in a series of (2-methanesulfonamidephenyl)piperazine derivatives that showed potent binding affinity and antagonistic activity for the Y5 receptor.
- Takahashi, Toshiyuki,Sakuraba, Aya,Hirohashi, Tomoko,Shibata, Takunobu,Hirose, Masaaki,Haga, Yuji,Nonoshita, Katsumasa,Kanno, Tetsuya,Ito, Junko,Iwaasa, Hisashi,Kanatani, Akio,Fukami, Takehiro,Sato, Nagaaki
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p. 7501 - 7511
(2007/10/03)
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