- Iron-catalyzed protodehalogenation of alkyl and aryl halides using hydrosilanes
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A simple and efficient iron-catalyzed protodehalogenation of alkyl and aryl halides using phenylhydrosilane is disclosed. The reaction utilizes FeCl3 without the requirement of ligands. Unactivated alkyl and aryl halides were successfully reduced in good yields; sterically hindered tertiary halides were also reduced including the less reactive chlorides. The scalability of this methodology was demonstrated by a gram-scale synthesis with a catalyst loading as low as 0.5 mol%. Notably, disproportionation of phenylsilane leads to diphenylsilane that further reduces the halides. Preliminary mechanistic studies revealed a non-radical pathway and the source of hydrogen is PhSiH3via deuterium labeling studies. Our methodology represents simplicity and provides a good alternative to typical tin, aluminum and boron hydride reagents.
- Pilli, Ramadevi,Balakrishnan, Venkadesh,Chandrasekaran, Revathi,Rasappan, Ramesh
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supporting information
p. 1749 - 1753
(2019/02/20)
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- Purple acid phosphatase inhibitors as leads for osteoporosis chemotherapeutics
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Purple acid phosphatases (PAPs) are metalloenzymes that catalyse the hydrolysis of phosphate esters under acidic conditions. Their active site contains a Fe(III)Fe(II) metal centre in mammals and a Fe(III)Zn(II) or Fe(III)Mn(II) metal centre in plants. In humans, elevated PAP levels in serum strongly correlate with the progression of osteoporosis and metabolic bone malignancies, which make PAP a target suitable for the development of chemotherapeutics to combat bone ailments. Due to difficulties in obtaining the human enzyme, the corresponding enzymes from red kidney bean and pig have been used previously to develop specific PAP inhibitors. Here, existing lead compounds were further elaborated to create a series of inhibitors with Ki values as low as ～30 μM. The inhibition constants of these compounds were of comparable magnitude for pig and red kidney bean PAPs, indicating that relevant binding interactions are conserved. The crystal structure of red kidney bean PAP in complex with the most potent inhibitor in this series, compound 4f, was solved to 2.40 ? resolution. This inhibitor coordinates directly to the binuclear metal centre in the active site as expected based on its competitive mode of inhibition. Docking simulations predict that this compound binds to human PAP in a similar mode. This study presents the first example of a PAP structure in complex with an inhibitor that is of relevance to the development of anti-osteoporotic chemotherapeutics.
- Hussein, Waleed M.,Feder, Daniel,Schenk, Gerhard,Guddat, Luke W.,McGeary, Ross P.
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p. 462 - 479
(2018/08/21)
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- Novel leucine ureido derivatives as aminopeptidase N inhibitors using click chemistry
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The over-expression of aminopeptidase N on diverse malignant cells is associated with the tumor angiogenesis and metastasis. In this report, one new series of leucine ureido derivatives containing the triazole moiety was designed, synthesized and evaluated as APN inhibitors. Among them, compound 13v showed the best APN inhibition with an IC50 value of 0.089 ± 0.007 μM, which was two orders of magnitude lower than that of bestatin (IC50 = 9.4 ± 0.5 μM). Compound 13v also showed dose-dependent anti-angiogenesis activities. Even at the lower concentration (10 μM), compound 13v presented similar anti-angiogenesis activity compared with bestatin at 100 μM in both the human umbilical vein endothelial cells (HUVECs) capillary tube formation assay and the rat thoracic aorta rings test. Moreover, compared with bestatin, 13v exhibited comparable, if not better in vivo anti-metastasis activity in a mouse H22 pulmonary metastasis model.
- Cao, Jiangying,Ma, Chunhua,Zang, Jie,Gao, Shuai,Gao, Qianwen,Kong, Xiujie,Yan, Yugang,Liang, Xuewu,Ding, Qin'ge,Zhao, Chunlong,Wang, Binghe,Xu, Wenfang,Zhang, Yingjie
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p. 3145 - 3157
(2018/06/01)
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- High diastereoselectivity in the yang photocyclization via remote hydrogen abstraction reaction
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1-Benzoyl-1-(o-alkoxyphenyl)cyclopropanes undergo Yang photocyclization to form dihydrobenzopyranols in a stereospecific manner. The cyclopropyl group at alpha position to carbonyls gives not only a bias in the most stable geometries of the starting ketones but also conformational restriction on geometries of biradical intermediates. More importantly, intramolecular hydrogen bonds seem to give an additional effect on conformational control of the biradical reactivity.
- Jang, Mi,Park, Bong Ser
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p. 1509 - 1514
(2016/10/09)
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- Synthesis of 5-arylisoxazole-3-carboxylates derived from salicylaldehyde
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A procedure has been developed for the synthesis of 5-arylisoxazole-3-carboxylates on the basis of phenols and oximes derived from salicylaldehyde. Selective reduction of 4-(2-ethoxybenzylideneaminophenyl) 5-arylisoxazole-3-carboxylates afforded the corresponding amines.
- Petkevich, S. K.,Dikusar, E. A.,Potkin, V. I.,Mikhei, I. V.
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- Pd-catalyzed reduction of aldehydes to alcohols using formic acid as the hydrogen donor
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Facile and selective reduction of aromatic aldehydes as well as aliphatic aldehydes to alcohols was achieved using formic acid as the hydrogen donor in the presence of a catalytic amount of Pd(OAc)2 and Cy3P. It was found that both hydrogen atoms in the formic acid molecule can serve as the hydride source. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for the following free supplemental resource(s): Full experimental and spectral details.]
- Wang, Anwei,Yang, Zhiyong,Liu, Jidan,Gui, Qingwen,Chen, Xiang,Tan, Ze,Shi, Ji-Cheng
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supporting information
p. 280 - 288
(2013/12/04)
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