1197-50-8Relevant academic research and scientific papers
Exploring Heteroaromatic Rings as a Replacement for the Labile Amide of Antiplasmodial Pantothenamides
Guan, Jinming,Spry, Christina,Tjhin, Erick T.,Yang, Penghui,Kittikool, Tanakorn,Howieson, Vanessa M.,Ling, Harriet,Starrs, Lora,Duncan, Dustin,Burgio, Gaetan,Saliba, Kevin J.,Auclair, Karine
, p. 4478 - 4497 (2021/05/04)
Malaria-causing Plasmodium parasites are developing resistance to antimalarial drugs, providing the impetus for new antiplasmodials. Although pantothenamides show potent antiplasmodial activity, hydrolysis by pantetheinases/vanins present in blood rapidly inactivates them. We herein report the facile synthesis and biological activity of a small library of pantothenamide analogues in which the labile amide group is replaced with a heteroaromatic ring. Several of these analogues display nanomolar antiplasmodial activity against Plasmodium falciparum and/or Plasmodium knowlesi, and are stable in the presence of pantetheinase. Both a known triazole and a novel isoxazole derivative were further characterized and found to possess high selectivity indices, medium or high Caco-2 permeability, and medium or low microsomal clearance in vitro. Although they fail to suppress Plasmodium berghei proliferation in vivo, the pharmacokinetic and contact time data presented provide a benchmark for the compound profile likely required to achieve antiplasmodial activity in mice and should facilitate lead optimization.
Visible-light mediated stereospecific C(sp2)-H difluoroalkylation of (Z)-aldoximes
Chen, Hua,Deng, Hongmei,Gong, Haiying,Hao, Jian,Li, Mingjie,Peng, Yi,Wan, Wen,Wang, Qian,Zhang, Yifang
supporting information, p. 7867 - 7874 (2021/09/28)
A visible light mediated stereospecific C(sp2)-H difluoroalkylation of (Z)-aldoximes to (E)-difluoroalkylated ketoximes has been described. In this reaction, (hetero)-aromatic and aliphatic difluoroalkylated ketoximes could be obtained with the retention of the configuration of the starting aldoximes. A preliminary mechanism study showed that a difluoromethyl radicalviaan SET pathway was involved.
SO2F2-Mediated one-pot cascade process for transformation of aldehydes (RCHO) to cyanamides (RNHCN)
Ding, Chengrong,Ge, Shuting,Wei, Junjie,Zhang, Guofu,Zhao, Yiyong
, p. 17288 - 17292 (2020/05/18)
A simple, mild and practical cascade process for the direct conversion of aldehydes to cyanamides was developed featuring a wide substrate scope and great functional group tolerability. This method allows for transformations of readily available, inexpensive, and abundant aldehydes to highly valuable cyanamides in a pot, atom, and step-economical manner with a green nitrogen source. This protocol will serve as a robust tool for the installation of the cyanamide moiety in various complicated molecules.
Unusual Reactivity of 4-Vinyl Isoxazoles in the Copper-Mediated Synthesis of Pyridines, Employing DMSO as a One-Carbon Surrogate
Kumar, Pravin,Kapur, Manmohan
supporting information, p. 5855 - 5860 (2020/07/30)
An efficient protocol for the synthesis of nicotinate derivatives and tetrasubstituted pyridines through a copper-mediated cleavage of isoxazoles has been developed. The highlight of the work is the observation of an unusual reactivity of 4-vinyl isoxazoles under the reaction conditions. DMSO serves as a one-carbon surrogate generating an active methylene group during the reaction to form two C-C bonds. This protocol provides a facile and an expeditious approach for the assembly of densely substituted N-heterocyclic compounds.
One-pot synthesis of aldoximes from alkenes: Via Rh-catalysed hydroformylation in an aqueous solvent system
Gr?ger, H.,Guntermann, A.,Hinzmann, A.,Jolmes, T.,Panke, D.,Plass, C.,R?sler, J.,Seidensticker, T.,Terhorst, M.,Vogt, D.,Vorholt, A. J.
supporting information, p. 7974 - 7982 (2020/11/30)
Aldoxime synthesis directly starting from alkenes was successfully achieved through the combination of hydroformylation and subsequent condensation of the aldehyde intermediate with aqueous hydroxylamine in a one-pot process. The metal complex Rh(acac)(CO)2 and the water-soluble ligand sulfoxantphos were used as the catalyst system, providing high regioselectivities in the initial hydroformylation. A mixture of water and 1-butanol was used as an environmentally benign solvent system, ensuring sufficient contact of the aqueous catalyst phase and the organic substrate phase. The reaction conditions were systematically optimised by Design of Experiments (DoE) using 1-octene as a model substrate. A yield of 85% of the desired linear, terminal aldoxime ((E/Z)-nonanal oxime) at 95% regioselectivity was achieved. Other terminal alkenes were also converted successfully under the optimised conditions to the corresponding linear aldoximes, including renewable substrates. Differences of the reaction rate have been investigated by recording the gas consumption, whereby turnover frequencies (TOFs) >2000 h-1 were observed for 4-vinylcyclohexene and styrene, respectively. The high potential of aldoximes as platform intermediates was shown by their subsequent transformation into the corresponding linear nitriles using aldoxime dehydratases as biocatalysts. The overall reaction sequence thus allows for a straightforward synthesis of linear nitriles from alkenes with water being the only by-product, which formally represents an anti-Markovnikov hydrocyanation of readily available 1-alkenes.
Stereospecific 1,4-Metallate Shift Enables Stereoconvergent Synthesis of Ketoximes
Yang, Kai,Zhang, Feng,Fang, Tongchang,Zhang, Guan,Song, Qiuling
supporting information, p. 13421 - 13426 (2019/08/20)
Reported herein is a stereospecific 1,4-metallate rearrangement for single-geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. In comparison with the conventional approaches, each configuration of unsymmetric diaryl oximes, as well as the thermodynamically less stable Z isomer of aryl alkyl ketoximes can be selectively and exclusively obtained. The reactivities of unsymmetric diaryl oximes and the Z isomer of aryl alkyl oximes, a class of underexplored molecules, enables efficient access to the corresponding isoquinolines, isoquinoline N-oxides, and amides having a single configuration.
SO 2 F 2 -Promoted Dehydration of Aldoximes: A Rapid and Simple Access to Nitriles
Ding, Chengrong,Mei, Guangyao,Wang, Haibo,Zhang, Guofu,Zhao, Yiyong
supporting information, p. 1484 - 1488 (2019/07/15)
A rapid, simple and mild process for the dehydration of aldoximes to give the corresponding nitriles, which utilizes SO 2 F 2 as an efficient reagent, has been developed. A variety of (hetero)arene, alkene, alkyne and aliphatic aldoximes proceeded with high efficiency to afford nitriles in excellent to quantitative yields with great functional group compatibilities in acetonitrile under ambient conditions. Furthermore, an eco-friendly synthetic protocol to access nitriles from aldehydes with ortho -, meta - and para -nitrile groups was also described in aqueous methanol by using inorganic base Na 2 CO 3, and a one-pot synthetic strategy to generate nitriles from aldehydes was proved to be feasible.
Facile One-Pot Transformation of Primary Alcohols into 3-Aryl- and 3-Alkyl-isoxazoles and -pyrazoles
Kobayashi, Eiji,Togo, Hideo
, p. 3723 - 3735 (2019/09/30)
Various primary alcohols were smoothly transformed into 3-aryl- and 3-alkylisoxazoles in good yields in one pot by successive treatment with PhI(OAc) 2 in the presence of TEMPO, NH 2 OH, and then NCS, followed by reaction with alkynes in the presence of Et 3 N. Similarly, various primary alcohols were smoothly transformed into 3-aryl- and 3-alkylpyrazoles in good yields in one pot by successive treatment with PhI(OAc) 2 in the presence of TEMPO, PhNHNH 2, and then NCS and decyl methyl sulfide, followed by reaction with alkynes in the presence of Et 3 N. Thus, both 3-aryl- and 3-alkylisoxazoles, and 3-aryl- and 3-alkylpyrazoles could be prepared from readily available primary alcohols in one pot under transition-metal-free conditions.
A mild system for synthesis of aldoximes and ketoximes in the presence of N-hydroxyphthalimide in aqueous system
Jiang, Xiaoying,Xu, Xiaohe,Lin, Yuyan,Yan, Yiyan,Li, Pingping,Bai, Renren,Xie, Yuanyuan
supporting information, p. 5879 - 5885 (2018/09/06)
An efficient method for synthesis of oximes from aldehydes or ketones with N-hydroxyphthalimide or N-hydroxysuccinimide in water has been described. It is the first time to utilize NHPI as an oximation reagent to synthesize aldoximes and ketoximes from the corresponding organic carbonyl compounds without other reagents. The reaction tolerates various functional groups and affords the corresponding oximes in 76%–98% yields. The by-product phthalic acid can be recycled from the system. In addition, this method has been successfully applied to the synthesis of the precursor of some pharmacologically active amide molecules.
Synthesis of Nitriles from Primary Amides or Aldoximes under Conditions of a Catalytic Swern Oxidation
Ding, Rui,Liu, Yongguo,Han, Mengru,Jiao, Wenyi,Li, Jiaqi,Tian, Hongyu,Sun, Baoguo
, p. 12939 - 12944 (2018/10/20)
The preparation of nitriles from primary amides or aldoximes was achieved by using oxalyl chloride with a catalytic amount of dimethyl sulfoxide in the presence of Et3N. The reactions were complete within 1 h after addition at room temperature. A diverse range of cyano compounds were obtained in good to excellent yields, including aromatic, heteroaromatic, cyclic, and acyclic aliphatic species.
