- CDPK1 INHIBITORS, COMPOSITIONS, AND METHODS RELATED THERETO
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The invention relates to inhibitors of calcium-dependent protein kinase 1 (CDPK1) and pharmaceutical preparations thereof. The invention further relates to methods of treatment of parasitic infections, such as T. gondii, P. falciparum, C. hominis, or C. parvum infections, using the novel inhibitors of the invention.
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Paragraph 0407-0410
(2021/11/13)
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- Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis
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Calcium dependent protein kinase 1 (CDPK1) is an essential Ser/Thr kinase that controls invasion and egress by the protozoan parasite Toxoplasma gondii. The Gly gatekeeper of CDPK1 makes it exquisitely sensitive to inhibition by small molecule 1H-pyrazolo
- Janetka, James W.,Hopper, Allen T.,Yang, Ziping,Barks, Jennifer,Dhason, Mary Savari,Wang, Qiuling,Sibley, L. David
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supporting information
p. 6144 - 6163
(2020/07/10)
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- Benzoxaborole Catalyst for Site-Selective Modification of Polyols
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The site-selective modification of polyols bearing several hydroxyl groups without the use of protecting groups remains a significant challenge in synthetic chemistry. To address this problem, novel benzoxaborole derivatives were designed as efficient catalysts for the highly site-selective and protecting-group-free modification of polyols. To identify the effective substituent groups enhancing the catalytic activity and selectivity, a series of benzoxaborole catalysts 1a–k were synthesized. In-depth analysis for the substituent effect revealed that 1i–k, bearing multiple electron-withdrawing fluoro- and trifluoromethyl groups, exhibited the greatest catalytic activity and selectivity. Moreover, 1i-catalyzed benzoylation, tosylation, benzylation, and glycosylation of various cis-1,2-diol derivatives proceeded with good yield and site-selective manner.
- Kusano, Shuhei,Miyamoto, Shoto,Matsuoka, Aki,Yamada, Yuji,Ishikawa, Ryuta,Hayashida, Osamu
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supporting information
p. 1598 - 1602
(2020/02/11)
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- Influence of Alcohol β-Fluorination on Hydrogen-Bond Acidity of Conformationally Flexible Substrates
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Rational modulations of molecular interactions are of significant importance in compound properties optimization. We have previously shown that fluorination of conformationally rigid cyclohexanols leads to attenuation of their hydrogen-bond (H-bond) donat
- Graton, Jerome,Compain, Guillaume,Besseau, Francois,Bogdan, Elena,Watts, Joseph M.,Mtashobya, Lewis,Wang, Zhong,Weymouth-Wilson, Alex,Galland, Nicolas,Le Questel, Jean-Yves,Linclau, Bruno
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supporting information
p. 2811 - 2819
(2017/03/05)
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- Lanthanide-based coordination polymers as promising heterogeneous catalysts for ring-opening reactions
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This work presents the synthesis and structural characterization of Eu3+- and Tb3+-based coordination polymers starting from a Co3+-based metalloligand offering appended arylcarboxylic acid groups. Both coordination polymers function as reusable heterogeneous catalysts for ring-opening reactions utilizing amines, alcohols, thiols, and azides as the nucleophiles. The catalytic results illustrate an excellent control over the regioselectivity whereas a filtration test and mechanistic studies substantiate Lewis-acid catalyzed activation of the epoxide during the reaction.
- Kumar, Gulshan,Kumar, Girijesh,Gupta, Rajeev
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p. 21352 - 21361
(2016/03/08)
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- Efficient and regioselective ring-opening of epoxides with alcohols and sodium azide by using catalytic amounts of gacl3/polyvinylpyrrolidone
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A new polymeric catalyst was prepared by supporting GaCl3 on cross-linked polyvinylpyrrolidone (GaCl3/ PVP). This catalyst was employed for efficient and regioselective ring-opening reaction of epoxides by various alcohols under solvent-free conditions at room temperature. In our procedure, this heterogeneous catalyst was used at neutral and mild reaction conditions to afford high yields of β-alkoxy alcohols. Also, regioselective conversion of epoxides to β-azidohydrines was accomplished by sodium azide in MeOH in the presence of GaCl3/PVP at room temperature. GaCl3/PVP is a non-hygroscopic and recoverable catalyst and is easily separated from reaction mixture by a simple filtration and re-used repeatedly. Also, this catalyst has good handling and can be stored for long time without any reducing of its reactivity.
- Pourali, Ali Reza,Ghayeni, Samaneh,Afghahi, Fatemeh
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p. 1741 - 1744
(2013/07/26)
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- Regioselective, borinic acid-catalyzed monoacylation, sulfonylation and alkylation of diols and carbohydrates: Expansion of substrate scope and mechanistic studies
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Synthetic and mechanistic aspects of the diarylborinic acid-catalyzed regioselective monofunctionalization of 1,2- and 1,3-diols are presented. Diarylborinic acid catalysis is shown to be an efficient and general method for monotosylation of pyranoside derivatives bearing three secondary hydroxyl groups (7 examples, 88% average yield). In addition, the scope of the selective acylation, sulfonylation, and alkylation is extended to 1,2- and 1,3-diols not derived from carbohydrates (28 examples); the efficiency, generality, and operational simplicity of this method are competitive with those of state-of-the-art protocols including the broadly applied organotin-catalyzed or -mediated reactions. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics, and catalyst structure-activity relationships. These experiments are consistent with a mechanism in which a tetracoordinate borinate complex reacts with the electrophilic species in the turnover-limiting step of the catalytic cycle.
- Lee, Doris,Williamson, Caitlin L.,Chan, Lina,Taylor, Mark S.
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supporting information; experimental part
p. 8260 - 8267
(2012/07/14)
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- Asymmetric synthesis of O-protected acyloins using enoate reductases: Stereochemical control through protecting group modification
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O-Protected cyclic acyloins were obtained in nonracemic form through asymmetric bioreduction of α,β-unsaturated alkoxy ketones by using 11 different enoate reductases from the "Old Yellow Enzyme" family. The stereochemical outcome of the biotransformation could be switched by variation of the O-protecting group or by the ring size of the substrate, which allows access to both stereoisomers in up to >97 % ee Whereas α-alkoxy enones were readily accepted as substrates, β-analogs were not converted. Overall, α-alkoxy enones represent a novel type of substrate for flavin-dependent ene-reductases. Copyright
- Winkler, Christoph K.,Stueckler, Clemens,Mueller, Nicole J.,Pressnitz, Desiree,Faber, Kurt
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experimental part
p. 6354 - 6358
(2011/02/24)
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- Synthesis, structures, and heterogeneous catalytic applications of {Co 3+-Eu3+} and {Co3+-Tb3+} heterodimetallic coordination polymers
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Two {Co3+-Eu3+} and {Co3+-Tb3+} heterodimetallic coordination polymers have been synthesized by using a Co 3+-based coordination complex as the building block. Structural studies show that the lanthanide atoms are coordinated to the cobalt complex through Oamide groups. This results in the generation of a one-dimensional zigzag coordination polymer. These coordination polymers have been shown to catalyze the ring-opening reactions of the epoxides with anilines and alcohols under heterogeneous and solvent-free conditions. Interestingly, a perfect regioselectivity was observed in the aminolysis and alcoholysis reaction of styrene oxide. Two {Co3+-Eu3+} and {Co 3+-Tb3+} zigzag coordination polymers have been synthesized by using a Co3+-based coordination complex. These coordination polymers have been shown to catalyze the ring-opening reactions of epoxides with anilines and alcohols under heterogeneous and solvent-free conditions.
- Kumar, Girijesh,Singh, Amit Pratap,Gupta, Rajeev
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experimental part
p. 5103 - 5112
(2011/02/17)
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- Catalytic monoalkylation of 1,2-diols
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A catalytic monoalkylation of 1,2-diols by using a weak base has been developed. Copper(II) dichloride and boronic acids are effective catalysts for activating 1,2-diols in the presence of potassium carbonate as a base. Various 1,2-diols were selectively monoalkylated with allyl-, benzyl- and alkyl- halides in DMF by choosing a suitable catalyst for each 1,2-diols.
- Maki, Toshihide,Ushijima, Nobuto,Matsumura, Yoshihiro,Onomura, Osamu
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experimental part
p. 1466 - 1468
(2009/05/31)
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- Copper-based metal-organic framework for the facile ring-opening of epoxides
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A simplified, facile route was applied for the synthesis of Cu(bpy)(H2O)2(BF4)2(bpy) [Cu-MOF] from Cu(BF4)2sH2O and 4,4′-bipyridine in aqueous ethanol. The Cu-MOF catalyst was characterized by XRD, elemental analysis, N2 adsorption, SEM, TEM, and electron diffraction. The crystalline Cu-MOF is an efficient catalyst in the ring-opening reactions of epoxides with alcohols and aniline under ambient, solvent-free conditions. The catalytic activity of Cu-MOF was comparable to that of the homogeneous catalyst Cu(BF4)2sH2O in the case of methanolysis, but the relative activity dropped significantly with increasing steric bulkiness of the alcohol, indicating the location of active sites in micropores. Although the catalyst was found to be truly heterogeneous and recyclable with no loss of activity, XRD revealed some restructuring due to interaction with methanol. This restructuring is attributed to the partial replacement of the structural water molecules by methanol, leading to significant changes in the H-bonding system of Cu-MOF.
- Jiang, Dongmei,Mallat, Tamas,Krumeich, Frank,Baiker, Alfons
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experimental part
p. 390 - 395
(2009/02/05)
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- Remaekable effect of subtle structural change of chiral pseudo-18-crown-6 on enantiomer-selectivity in complexation with chiral amino alcohols
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Chiral receptors [(S,S)-1] and [(S,S,S,S)-2] having 1,2-dialkoxy-1-(3,5-dimethylphenyl)ethane and 1,2-dialkoxy-1-(3,5-dimethyl phenyl)cyclohexane as chiral building blocks, respectively, were prepared. Thermodynamic parameters of complexations of these and structurally related receptors [(S,S)-3] and [(S,S,S,S)-4] with 2-amino-l-propanol (5), 2-amino-2-phenylethanol (6), and 3-methylbutan-l-ol (7) in chloroform were determined. It was found that the host-guest systems that have same enantiomer-selectivity at 25°C showed opposite selectivity in the enthalpy term. For example, complexations of both (S,S)-1 and (S,S)-3 with 5 are R-selective at 25°C (ΔΔG = 2.2 and 3.8 kJ mol-1, respectively), whereas in terms of the enthalpy of complexation the former is S-selective (ΔΔH = 22 kJ mol-1) but the latter is R-selective (ΔΔH = 10 kJ mol-1).
- Hirose, Keiji,Aksharanandana, Pakatip,Suzuki, Michiko,Wada, Kiyoshi,Naemura, Koichiro,Tobe, Yoshito
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p. 405 - 431
(2007/10/03)
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- Carbon tetrabromide: An efficient catalyst for regioselective ring opening of epoxides with alcohols and water
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Epoxides undergo rapid ring opening with a range of alcohols in the presence of catalytic amount of carbon tetrabromide under mild and convenient conditions to afford the corresponding β-alkoxy alcohols and 1,2-diols in high yields with high regioselectivity. Georg Thieme Verlag Stuttgart.
- Yadav,Reddy,Harikishan,Madan,Narsaiah
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p. 2897 - 2900
(2007/10/03)
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- Copper(II) tetrafluoroborate catalyzed ring-opening reaction of epoxides with alcohols at room temperature
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(figure presented) Efficient ring opening of different epoxides by reaction with representative alcohols is presented. These processes were carried out at room temperature and rely on the usefulness of commercial copper tetrafluoroborate as catalyst.
- Barluenga, Jose,Vazquez-Villa, Henar,Ballesteros, Alfredo,Gonzalez, Jose M.
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p. 2817 - 2819
(2007/10/03)
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- Synthesis of chiral trans-anti-trans-isomers of dicyclohexano-18-crown-6 via an enzymatic reaction and the solid-state structure of one enantiomer
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Chiral trans-anti-trans-dicyclohexano-18-crown-6 isomers are synthesized via a lipase-catalyzed reaction. The solid-state structure of the (S)-enantiomer is determined and compared with those reported for 18-crown-6 and trans-syn-trans-dicyclohexano-18-crown-6.
- Yamato, Kazuhiro,Bartsch, Richard A.,Broker, Grant A.,Rogers, Robin D.,Dietz, Mark L.
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p. 5805 - 5808
(2007/10/03)
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- Improved conditions for the addition of alkoxides to di(ethylene glycol) di-p-tosylate: Application to the stereospecific synthesis of the trans-isomers of dicyclohexano-18-crown-6
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Conditions are defined for the efficient preparation of polyethers by direct condensation of ditosylates and alkoxides, and this approach is shown to provide a facile method for the synthesis of the trans-syn-trans (C) and trans-anti-trans (D) isomers of
- Huber, Vincent J.,Dietz, Mark L.
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p. 2945 - 2948
(2007/10/03)
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- Regiochemical control of the ring opening of 1,2-epoxides by means of chelating processes. Part 14: Regioselectivity of the opening reactions with MeOH of remote O-substituted 1,2-epoxycyclohexanes under gas-phase operating conditions
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The regiochemical behavior of cyclohexene oxides bearing a remote O-functionality was determined in the gas-phase in opening reactions with MeOH, using a gaseous acid (D3/+, C(n)H5/+, Me2F+
- Crotti, Paolo,Di Bussolo, Valeria,Favero, Lucilla,Pineschi, Mauro,Marianucci, Francesco,Renzi, Gabriele,Amici, Giuseppina,Roselli, Graziella
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p. 7513 - 7524
(2007/10/03)
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- Alcoholysis of Epoxides Catalyzed by Tetracyanoethylene and Dicyanoketene Acetals
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A typical π-acid tetracyanoethylene and capto-dative olefin dicyanoketene acetals were found to catalyze stereospecific alcoholysis of epoxides at the ambient temperature to 50°C in good yields. Mildness and significant chemoselectivity of the catalysts were demonstrated by intactness of tetrahydropyranyl ether and ethylene acetal groups. A novel regioselectivity associated with anchimeric assistance of the ethereal group on the side chain was observed in the ring opening reaction of the 1,2-disubstituted epoxides.
- Masaki, Yukio,Miura, Tsuyoshi,Ochiai, Masahito
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p. 195 - 205
(2007/10/03)
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- Preparation and Enantiomer Recognition Behaviour of Azophenolic Crown Ethers containing cis-Cyclohexane-1,2-diol as a Chiral Centre
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Both enentiomers of the azophenolic crown ether 1 incorporating the cis-cyclohexane-1,2-diol residue as the chiral centre have been prepared in enantiomerically pure forms and the chiral recognition behaviour towards 2-aminoethanols and ethylamines has be
- Naemura, Koichiro,Takeuchi, Sachiko,Hirose, Keiji,Tobe, Yoshito,Kaneda, Takahiro,Sakata, Yoshiteru
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p. 213 - 220
(2007/10/02)
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- Regiochemical control of the ring opening of 1,2-epoxides by means of chelating processes. 8. Synthesis and ring opening reactions of cis- and trans-oxides derived from 3-benzyloxycyclohexene and 2-benzyloxy-5,6-dihydro-2H-pyran
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The regiochemical outcome of the ring opening of 1,2-epoxides bearing polar remote functionalization through chelation processes assisted by metal ions, was verified in cyclic oxirane systems having the polar functionality in an allylic position to the oxirane ring. The diastereoisomeric cis/trans epoxide pairs 5,6 and 7,8 derived from 3-benzyloxycyclohexene, and 2-benzyloxy-5,6-dihydro-2H-pyran, respectively, were prepared and several of their opening reactions were studied. The regioselectivity observed largely depends on the reaction conditions (standard or metal-assisted) and, interestingly, on the nature of the nucleophile used.
- Calvani, Federico,Crotti, Paolo,Gardelli, Cristina,Pineschi, Mauro
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p. 12999 - 13022
(2007/10/02)
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- Pig liver acetone powder (PLAP) as biocatalyst: Enantioselective synthesis of trans-2-alkoxycyclohexan-1-ols
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Pig liver acetone powder (PLAP) enantioselectively hydrolyzes trans-1- acetoxy-2-alkoxycyclohexanes 1a-6a in biphasic medium (ether and phosphate buffer) to provide the required (1R,2R)-2-alkoxycyclohexan-1-ols in 61-82% enantiomeric purities.
- Basavaiah, Deevi,Krishna, Peddinti Rama
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p. 10521 - 10530
(2007/10/02)
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- Enantiomerically Pure Cyclohexanols and Cyclohexane-1,2-Diol Derivatives; Chiral Auxiliaries and Substitutes for (-)-8-Phenylmenthol. A Facile Enzymatic Route
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A number of optically active cyclohexanol and cyclohexane-1,2-diol derivatives, chiral auxiliaries and substitutes for (-)- and (+)-8-phenylmenthol, have been prepared by enzymatic hydrolysis of their racemic acetates and chloroacetates in the presence of a highly selective ester hydrolase from Pseudomonas sp. (SAM-II).
- Laumen, Kurt,Breitgoff, Detlef,Seemayer, Robert,Schneider, Manfred P.
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p. 148 - 150
(2007/10/02)
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- Hydroboration of Vinyl Ethers with Diisopinocampheylborane
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The reactions of diisopinocampheylborane with cyclic vinyl ethers having an exocyclic oxygen and with acyclic vinyl ethers having groups of varying size attached to oxygen were explored.Evidence of some interaction of the bulkier vinyl ethers with diisopinocampheylborane was obtained, but high enantiomeric excesses were not found.However, the hydroboration-oxidation of benzyl or diphenylmethyl vinyl ethers, followed by cleavage, is a practical route to partially resolved diols.
- Peterson, Paul E.,Stepanian, Marshall
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p. 1903 - 1907
(2007/10/02)
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