- 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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- 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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- Dihydroquinozinone carboxylic acid compound and application thereof (by machine translation)
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The invention belongs to the field of, pharmaceutical chemistry, and relates to (HBV) a dihydroquinozinone carboxylic acid compound with the activity of, and resisting hepatitis B virus (hepatitis B virus) .and a preparation method of the dihydroquinozino
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Paragraph 0078-0081
(2020/02/14)
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- Glycidyl Tosylate: Polymerization of a “Non-Polymerizable” Monomer permits Universal Post-Functionalization of Polyethers
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Glycidyl tosylate appears to be a non-polymerizable epoxide when nucleophilic initiators are used because of the excellent leaving group properties of the tosylate. However, using the monomer-activated mechanism, this unusual monomer can be copolymerized
- Jung, Philipp,Ziegler, Arthur D.,Blankenburg, Jan,Frey, Holger
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supporting information
p. 12883 - 12886
(2019/08/22)
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- Chiral ND - 322, ND - 364 or ND - 364 sulfoxide analogs and its preparation method
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The invention relates to a chiral ND-322, ND-364 or ND-364 sulfoxide analog and a preparation method therefor, and belongs to the technical field of pharmaceutical active compound synthesis. The chiral ND-322, ND-364 or ND-364 sulfoxide analog takes chira
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Paragraph 0121; 0122
(2018/04/02)
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- An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors
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Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b]pyrimido[5,4-f]azepine and two alkyl{3-/4-[1-hydroxy-2-(4-arylpiperazin-1-yl)ethyl]phenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analyses indicate that the cationic head of the different compounds must be refined in order to obtain an increase in the binding affinity of these ligands.
- Vettorazzi, Marcela,Angelina, Emilio,Lima, Santiago,Gonec, Tomas,Otevrel, Jan,Marvanova, Pavlina,Padrtova, Tereza,Mokry, Petr,Bobal, Pavel,Acosta, Lina M.,Palma, Alirio,Cobo, Justo,Bobalova, Janette,Csollei, Jozef,Malik, Ivan,Alvarez, Sergio,Spiegel, Sarah,Jampilek, Josef,Enriz, Ricardo D.
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p. 461 - 481
(2017/08/21)
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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 and characterization of new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates and their hydrochloride salts
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Five new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates were designed and synthesized as potential dual antihypertensive agents. The compounds were prepared as free bases and subsequently transformed to hydrochloride salts. The position of pr
- Marvanova, Pavlina,Padrtova, Tereza,Pekarek, Tomas,Brus, Jiri,Czernek, Jiri,Mokry, Petr,Humpa, Otakar,Oravec, Michal,Jampilek, Josef
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- Synthesis and determination of physicochemical properties of new 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-alkoxyethoxybenzoates
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Nine new dihydrochloride salts of 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-alkoxyethoxybenzoates were designed and synthesized. The physicochemical properties such as lipophilicity index (log kw) and dissociation constant (pKa) wer
- Marvanova, Pavlina,Padrtova, Tereza,Odehnalova, Klara,Hosik, Ondrej,Oravec, Michal,Mokry, Petr
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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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- Total Synthesis of (+)-Cryptocaryol A Using a Prins Cyclization/Reductive Cleavage Sequence
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The total synthesis of (+)-cryptocaryol A was achieved in 20 steps from (R)-glycidol. The key steps were a Prins cyclization/reductive cleavage sequence to construct the C5-C11 polyol fragment, a diastereoselective aldol reaction to control the stereogeni
- Brun, Elodie,Bellosta, Véronique,Cossy, Janine
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p. 8668 - 8676
(2015/09/15)
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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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- Light-mediated total synthesis of 17-deoxyprovidencin
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An asymmetric synthesis of the diterpenoid 17-deoxyprovidencin is described. Key steps include an aldol addition, a base-catalyzed Wipf-type furan formation, a Z-selective ring-closing metathesis for macrocyclization, a photochemical E/Z isomerization to a highly strained and conformationally restricted ring system, and the stereoselective formation of two epoxides on the ring. Photochemistry is the key: An asymmetric synthesis of the diterpenoid 17-deoxyprovidencin is described. Key steps include an aldol addition, a base-catalyzed Wipf-type furan formation, a Z-selective ring-closing metathesis for macrocyclization, a photoinduced Z/E isomerization to a highly strained conformationally restricted ring system, and the stereoselective formation of two epoxides on the macrocycle.
- Toelle, Nina,Weinstabl, Harald,Gaich, Tanja,Mulzer, Johann
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supporting information
p. 3859 - 3862
(2014/05/06)
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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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- Hf(IV)-catalyzed enantioselective epoxidation of N-alkenyl sulfonamides and N-tosyl imines
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Asymmetric epoxidation of allylic and homoallylic amine derivatives catalyzed by Hf(IV)-bishydroxamic acid complexes is described. Under similar conditions, aldimine and ketimine produced oxaziridines. The sulfonyl group is demonstrated to be an effective directing group for these transformations.
- Olivares-Romero, Jose Luis,Li, Zhi,Yamamoto, Hisashi
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supporting information; experimental part
p. 5440 - 5443
(2012/05/20)
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- Application of the Rodriguez-Pattenden photo-ring contraction: Total synthesis and configurational reassignment of 11-gorgiacerol and 11-epigorgiacerol
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A stereospecific photochemical ring contraction was used as the key step in the first total synthesis of the marine pseudopteranyl diterpene 11-gorgiacerol and its 11-epimer. The synthesis allowed the correction of the configurations that had been misassigned in the literature. In addition, some novel pseudopteranyl derivatives have been made.
- Weinstabl, Harald,Gaich, Tanja,Mulzer, Johann
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supporting information; experimental part
p. 2834 - 2837
(2012/07/28)
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- A safe two-step process for manufacturing glycidyl nitrate from glycidol involving solid-liquid phase-transfer catalysis
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A new and safer two-step process for manufacturing glycidyl nitrate from glycidol is reported. In the first step glycidyl tosylate is obtained by reacting glycidol with p-tosyl chloride in the presence of triethylamine according to any one of the well-known procedures for obtaining tosyl esters described in the literature. In the second step, glycidyl tosylate is reacted with NaNO3 in refluxing acetonitrile under solid-liquid phase-transfer catalysis conditions using tetrabutylammonium nitrate as catalyst. Acetonitrile and the phase-transfer catalyst were recycled 12 times without deactivation, yielding 99% pure glycidyl nitrate in a cumulative isolated yield of 81.5% with a catalyst turnover number of 85.7 mol substrate per mol phase-transfer catalyst. This procedure avoids the use of the dangerous reactants used in the current manufacturing processes of glycidyl nitrate and could be useful as a safe and general method for obtaining nitrate esters.
- Ochoa-Gomez, Jose R.,Blanco-Gomez, Juan J.
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scheme or table
p. 1454 - 1457
(2012/01/12)
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- Therapeutic quinazoline derivatives
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A compound of formula (I) or a salt, ester, amide or prodrug thereof; where X is O, or S, S(O), S(O)2 or NR6 where R6 is hydrogen of C1-6alkyl; R5 is an optionally substituted 6-membered aromatic ring containing at least one nitrogen atom, and R1, R2, R3, R4 are independently selected from halogeno, cyano, nitro, C1-3alkylsulphanyl, —N(OH)R7— (wherein R7 is hydrogen, or C1-3alkyl), or R9X1— (wherein X1 represents a direct bond, —O—, —CH2—, —OC(O), —C(O)—, —S—, —SO—, —SO2—, —NR10C(O)—, —C(O)NR11—, —SO2NR12—, —NR13SO2— or NR14— (wherein R10, R11, R12, R13 and R14 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), and R9 is hydrogen, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or optionally substituted alkoxy; provided that at least one of R2 or R3 is other than hydrogen. These compounds inhibit aurora 2 kinase and are useful in the preparation of medicaments for the treatment of proliferative disease such as cancer.
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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 7-8
(2008/06/13)
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- Poly(per)fluoroalkanesulfonyl fluoride promoted olefin epoxidation with 30% aqueous hydrogen peroxide
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Epoxidation of various electron rich olefins with a novel oxidation system of poly(per)fluoroalkanesulfonyl fluoride/hydrogen peroxide/base is reported.
- Yan, Zhaohua,Tian, Weisheng
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p. 2211 - 2213
(2007/10/03)
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- Synthesis and noncovalent DNA-binding properties of thiazole derivatives related to leinamycin
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A series of compounds related to the macrocyclic portion of the DNA-damaging antitumor agent leinamycin were prepared as tools to characterize noncovalent DNA binding by this natural product. Acyclic (Z,E)-dienes were assembled via a Sonogashira coupling followed by partial hydrogenation. A Stille coupling was used in the cyclization step leading to a macrocyclic thiazole-diene analogue. Results obtained using the synthetic analogues reported here indicate that the extended π-system on the 'left-hand side' of leinamycin is required for noncovalent association of the natural product with duplex DNA.
- Breydo, Leonid,Zang, Hong,Gates, Kent S.
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p. 5711 - 5716
(2007/10/03)
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- Synthesis and antibacterial evaluation of oxazolidin-2-ones structurally related to linezolid
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Compounds structurally related to the known antimicrobial drug linezolid were selected in order to evaluate the influence of electron-withdrawing properties and altered geometric features as a result of the N-substituent modification. After a preliminary
- Ammazzalorso, Alessandra,Amoroso, Rosa,Bettoni, Giancarlo,Fantacuzzi, Marialuigia,De Filippis, Barbara,Giampietro, Letizia,Maccallini, Cristina,Paludi, Domenico,Tricca, Maria L.
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p. 685 - 690
(2007/10/03)
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- Process for preparation of glycidyl sulfonate derivative
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A process for preparation of a glycidyl sulfonate derivative with high purity and in high yield, which is characterized in reacting glycidol which is prepared from treating 3-chloro-1,2-propanediol in an aqueous solvent in the basic condition, without iso
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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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