- An Unexpected Transannular [4+2] Cycloaddition during the Total Synthesis of (+)-Norcembrene 5
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We report a concise and versatile total synthesis of the diterpenoid (+)-norcembrene 5 from simple building blocks. Ring-closing metathesis and an auxiliary-directed 1,4-addition are the key steps of our synthetic route. During the synthesis, an unprecede
- Breunig, Michael,Gaich, Tanja,Yuan, Po
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supporting information
p. 5521 - 5525
(2020/02/20)
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- Development of Selective Steroid Inhibitors for the Glucose-6-phosphate Dehydrogenase from Trypanosoma cruzi
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Chagas disease is a parasitic infection affecting millions of people across Latin America, imposing a dramatic socioeconomic burden. Despite the availability of drugs, nifurtimox and benznidazole, lack of efficacy and incidence of side-effects prompt the identification of novel, efficient, and affordable drug candidates. To address this issue, one strategy could be probing the susceptibility of Trypanosoma parasites toward NADP-dependent enzyme inhibitors. Recently, steroids of the androstane group have been described as highly potent but nonselective inhibitors of parasitic glucose-6-phosphate dehydrogenase (G6PDH). In order to promote selectivity, we have synthesized and evaluated 26 steroid derivatives of epiandrosterone in enzymatic assays, whereby 17 compounds were shown to display moderate to high selectivity for T. cruzi over the human G6PDH. In addition, three compounds were effective in killing intracellular T. cruzi forms infecting rat cardiomyocytes. Altogether, this study provides new SAR data around G6PDH and further supports this target for treating Chagas disease.
- Fredo Naciuk, Fabrício,Do Nascimento Faria, Jéssica,Gonc?lves Eufrásio, Amanda,Torres Cordeiro, Artur,Bruder, Marjorie
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supporting information
p. 1250 - 1256
(2020/07/27)
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- Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety
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Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.
- Zhu, Lunan,Zhu, Junchen,Sun, Xiaotong,Wu, Yaling,Wang, Huiying,Cheng, Lingping,Shen, Jiawei,Ke, Yanxiong
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p. 1080 - 1090
(2020/05/25)
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- Method for manufacturing optically active cyclic ether ester derivative
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The invention provides a method for simply and selectively manufacturing an optically active cyclic ether aryl sulfonic acid ester with an inexpensively obtained racemate as the raw material. The method for manufacturing the cyclic ether aryl sulfonic acid ester comprises the steps of with the existence of optically active bisoxazoline ligand, lewis acid compound, alkali and organic solvent, aryl sulfonyl halide and hydroxymethyl cyclic ether are subjected to the racemate reaction to obtain an optically active cyclic ether aryl sulfonic acid ester. Preferably glycidyl or 2-hydroxymethyl tetrahydrofuran is adopted as the above hydroxymethyl cyclic ether.
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Paragraph 0100; 0101; 0102
(2017/01/02)
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- Synthesis of chiral ND-322, ND-364 and ND-364 derivatives as selective inhibitors of human gelatinase
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Compounds 10 (ND-322) and 15 (ND-364) are potent selective inhibitors for gelatinases, matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). However, both of them are racemates. Herein we report facile synthesis of optically active (R)-
- Yan, Yugang,Chen, Xueying,Yang, Xinying,Zhang, Jian,Xu, Wenfang,Zhang, Yingjie
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p. 6632 - 6640
(2015/10/19)
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- Diastereo- and enantioselective synthesis of 1,3,5,7-tetraol structural units using a Prins cyclisation-reductive cleavage sequence
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Stereocontrolled and efficient access to all the diastereomers of 1,3,5,7-tetraol structural units was developed using a Prins cyclisation-reductive cleavage sequence applied to tetrahydropyran aldehydes. Furthermore, these tetraols can be selectively functionalized. This journal is the Partner Organisations 2014.
- Brun, Elodie,Bellosta, Véronique,Cossy, Janine
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supporting information
p. 6718 - 6721
(2014/06/23)
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- PROCESSES AND INTERMEDIATES FOR PREPARING RIVAROXABAN
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The invention discloses processes for the preparation of rivaroxaban and its pharmaceutically acceptable salts, solvates, and hydrates thereof. The invention also relates to novel intermediates for the preparation of rivaroxaban.
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Paragraph 0205; 0206
(2015/01/07)
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- Towards dual antithrombotic compounds-Balancing thrombin inhibitory and fibrinogen GPIIb/IIIa binding inhibitory activities of 2,3-dihydro-1,4- benzodioxine derivatives through regio- and stereoisomerism
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Enantiomers of 2,3-dihydro-1,4-benzodioxine derivatives possessing both thrombin and fibrinogen GPIIb/IIIa binding inhibitory activities were prepared from (R)- and (S)-glycidol as potential dual antithrombotic compounds. The influence of chirality and su
- Ilic, Milos,Dunkel, Petra,Ilas, Janez,Chabielska, Ewa,Zakrzeska, Agnieszka,Matyus, Peter,Kikelj, Danijel
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p. 329 - 340
(2013/05/22)
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- PROCESSES AND INTERMEDIATES FOR PREPARING RIVAROXABAN
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The invention discloses processes for the preparation of rivaroxaban and its pharmaceutically acceptable salts, solvates, and hydrates thereof. The invention also relates to novel intermediates for the preparation of rivaroxaban.
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Page/Page column 40-41
(2013/07/19)
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- PROCESS FOR THE PREPARATION OF GLYCIDYL DERIVATIVES
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There is provided a process for preparing a glycidyl derivative from 3-chloro-1,2-propanediol, comprising i) adding a phosphate salt to a solution into which 3-chloro-1,2-propanediol is dissolved into a solvent to produce glycidol, and ii) adding to the solution of step i) a base capable of releasing a glycidyl group from the glycidol and a substrate susceptible to nucleophilic attack to produce the desired glycidyl derivative by nucleophilic attack of the glycidyl group to the substrate.
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Page/Page column 8
(2008/06/13)
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- Scavenger assisted combinatorial process for preparing libraries of tertiary amine compounds
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This invention relates to a novel solution phase process for the preparation of tertiary amine combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Process for production of glycide derivative
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A glycide derivative represented by the following general formula (I) is produced by reacting a hydroxyaryl or heteroaryl represented by A-OH with glycidyl tosylate in the presence of a cesium base as a base. Thereby, an aryl glycidyl ether derivative, which is an important intermediate for drug production, can be produced easily and reliably. Particularly when optically active glycidyl tosylate is used, said compound can be obtained at a high optical purity. STR1 wherein A represents an aryl group or a heteroaryl group.
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- Catalytic Asymmetric Epoxidation and Kinetic Resolution: Modified Procedures Including in Situ Derivatization
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The use of 3A or 4A molecular sieves ( zeoiltes ) substantially increases the scope of the titanium(IV)-catalyzed asymmetric epoxidation of primary allylic alcohols.Whereas without molecular sieves epoxidations employing only 5 to 10 mol percent Ti(O-i-Pr)4 generally led to low conversion or low enantioselectivity, in the presence of molecular sieves such reactions generally led to high conversion (>95percent) and high enantioselectivity (90-95percent ee).The epoxidations of 20 primary allylic alcohols are described.Especially noteworthy are the epoxidations of cinnamyl alcohol, 2-tetradecyl-2-propen-1-ol, allyl alcohol, and crotyl alcohol-compounds which heretofore had been considered difficult substrates for asymmetric epoxidation.In the case of allylic alcohol, the use of cumene hydroperoxide substantially increases both the reaction rate and the conversion, even in the absence of molecular sieves.In general, enantioselectivities are slightly depressed (by 1-5percent ee) relative to reactions employing 50-100 mol percent Ti(O-i-Pr)4.The epoxidation of low molecular weight allylic alcohols is especially facilitated and, in conjuction with in situ derivatization, provides for the synthesis of many epoxy alcohol synthons which were previously difficult to obtain.The kinetic resolution of four secondary allylic alcohols with 10 mol percent Ti(O-i-Pr)4 is also described.The role of molecular sieves in the reaction and the effects of variation in reaction stoichiometry, oxidant, and tartrate are discussed.
- Gao, Yun,Hanson, Robert M.,Klunder, Janice M.,Ko, Soo Y.,Masamune, Hiroko,Sharpless, K. Barry
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p. 5765 - 5780
(2007/10/02)
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