- Chiral Bicyclic Imidazole-Catalyzed Acylative Dynamic Kinetic Resolution for the Synthesis of Chiral Phthalidyl Esters
-
Utilizing a chiral bicyclic imidazole organocatalyst and adopting a continuous injection process, an alternative route has been developed for the efficient synthesis of chiral phthalidyl ester prodrugs via dynamic kinetic resolution of 3-hydroxyphthalides through enantioselective acylation (up to 99 % ee). The computational studies suggest a general base catalytic mechanism differing from the widely accepted nucleophilic catalytic mechanism. The structure analysis of the key transition states shows that the CH-π interactions and not the previously considered cation/π-π interactions between the catalyst and substrate is the dominant factor giving rise to the observed stereocontrol.
- Zhou, Muxing,Gridneva, Tatiana,Zhang, Zhenfeng,He, Ende,Liu, Yangang,Zhang, Wanbin
-
supporting information
p. 1641 - 1645
(2020/11/30)
-
- Visible Light-Promoted Magnesium, Iron, and Nickel Catalysis Enabling C(sp3)-H Lactonization of 2-Alkylbenzoic Acids
-
A mild and practical C(sp3)-H lactonization protocol has been achieved by merging photocatalysis and magnesium (iron, nickel) catalysis. A diverse range of 2-alkylbenzoic acids with a variety of substitution patterns could be transformed into the corresponding phthalide products. Based on the mechanistic experimentation and reported prior studies, a possible mechanism for the benzylic oxidative lactonization reaction was proposed with the hypothetic photoactive ternary complex formed between the 2-alkylbenzoic acid substrate, magnesium ion, and bromate anion.
- Li, Sasa,Su, Mincong,Sun, Jie,Hu, Kunjun,Jin, Jian
-
supporting information
p. 5842 - 5847
(2021/07/31)
-
- Squaramide-catalyzed asymmetric intramolecular oxa-michael reaction of α,β-unsaturated carbonyls containing benzyl alcohol: Construction of chiral 1-substituted phthalans
-
Organocatalytic enantioselective intramolecular oxa-Michael reactions of benzyl alcohol bearing α,β-unsaturated carbonyls as Michael acceptors are presented herein. Using cinchona squaramide-based organocatalyst, enones as well as α,βunsaturated esters containing benzyl alcohol provided their corresponding 1,3-dihydroisobenzofuranyl-1-methylene ketones and 1,3-dihydroisobenzofuranyl-1-methylene esters in excellent yields with high enantioselectivities. In addition, enantioenriched 1,3-dihydroisobenzofuranyl-1-methylene ketone could be obtained from the Wittig/oxa-Michael reaction cascade of 1,3-dihydro-2-benzofuran-1-ol.
- Son, Eun Chae,Kim, Seung Yeon,Kim, Sung-Gon
-
p. 6826 - 6839
(2021/05/29)
-
- Organocatalytic enantioselective synthesis of phthalans via Wittig/oxa-Michael cascade reaction
-
An enantioselective synthetic method for 1-substituted phthalans has been developed. The organocatalytic reaction between 1,3-dihydro-2-benzofuran-1-ols and Wittig reagents using cinchona squaramide-based organocatalyst proceeded with sequential Wittig reaction followed by an enantioselective intramolecular oxa-Michael reaction, yielding enantioenriched phthalans with moderate to good enantioselectivities.
- Son, Eun Chae,No, Jaeeun,Kim, Sung-Gon
-
p. 1473 - 1480
(2021/09/25)
-
- Synthesis of 3-Unsubstituted Phthalides from Aryl Amides and Paraformaldehyde via Ruthenium(II)-Catalyzed C–H Activation
-
A straightforward and convenient route has been developed for the synthesis of 3-unsubstituted phthalide derivatives from aryl amides and paraformaldehyde by ruthenium(II)-catalyzed C–H activation. The reaction proceeds through tandem ortho-hydroxymethylation of aryl amide and subsequent intramolecular lactonization.
- Zhou, Chao,Zhao, Junqi,Chen, Wenkun,Imerhasan, Mukhtar,Wang, Jun
-
supporting information
p. 6485 - 6488
(2020/10/02)
-
- IDO/TDO Inhibitor
-
A compound of formula (I) given below or a pharmaceutically acceptable salt of the compound is useful as an IDO/TDO inhibitor. Thus, the compound of formula (I) or the pharmaceutically acceptable salt of the compound can be used as, for example, a therapeutic agent for a disease or a disorder selected from tumor, infectious disease, neurodegenerative disorder, cataract, organ transplant rejection, autoimmune disease, postoperative cognitive impairment, and disease related to women's reproductive health [in the following formula (I), ring A represents an aromatic ring, an aliphatic ring, a heterocyclic ring, or a condensed ring of two or more rings selected from an aromatic ring, an aliphatic ring and a heterocyclic ring; X, R1 and R2 represent a substituent on a ring atom constituting ring A; m represents an integer of 0 to 6; X represents, for example, a halogen atom; and R1 and R2 are the same or different and are selected from, for example, the group consisting of groups of formula (a) or formula (b); and in the following formula (a) and formula (b), Y is selected from the group consisting of O, S, and Se, Z is selected from the group consisting of O, S, and Se, n represents an integer of 1 to 8, r represents an integer of 1 to 8, s represents an integer of 1 to 8, R4 represents, for example, —C(═NH)—HN2, and R6 represents, for example, a substituted or unsubstituted aryl group].
- -
-
Paragraph 0906-0909
(2020/08/19)
-
- A g-C3N4-based heterogeneous photocatalyst for visible light mediated aerobic benzylic C-H oxygenations
-
A metal-free heterogeneous photocatalytic system has been developed for highly efficient benzylic C-H oxygenations using oxygen as an oxidant. This visible light mediated oxidation reaction utilizes graphitic carbon nitride (g-C3N4) as a recyclable, nontoxic and low cost photocatalyst. Mild reaction conditions allow for the generation of synthetically and biologically valued isochromannones, phthalides, isoquinolinones, isoindolinones and xanthones from readily accessible alkyl aromatic precursors in good yields. The heterogeneous nature of the g-C3N4 catalytic system enables easy recovery and recycling as well as the use in multiple runs without loss of activity. The synthetic utility of this "green" methodology was further demonstrated by applying in bioactive and drug valued target syntheses.
- Geng, Pengxin,Tang, Yurong,Pan, Guanglong,Wang, Wentao,Hu, Jinchuan,Cai, Yunfei
-
supporting information
p. 6116 - 6122
(2019/11/20)
-
- Platinum-on-Carbon-Catalyzed Aqueous Oxidative Lactonization of Diols by Using Molecular Oxygen
-
A lactonization of various diols catalyzed by platinum on carbon (Pt/C) in water under an atmosphere of molecular oxygen was developed. Derivatives of 1,4- 1,5- and 1,6-diols were transformed into the corresponding five-, six-, and seven-membered lactones by the present oxidative lactonization method.
- Ban, Kazuho,Sajiki, Hironao,Sawama, Yoshinari,Takakura, Ryoya
-
supporting information
p. 1919 - 1923
(2019/09/30)
-
- 6 - [...] indoline - 1 - one synthetic method
-
The invention provides a synthesis method of 6-bromoisoindolinyl-1-one, which comprises the following steps: (a) carrying out substitution reaction on a compound (I) and a bromination reagent in an organic solvent to obtain a compound (IIa)-compound (IIb) mixture; (b) carrying out hydrolysis reaction on the compound (IIa)-compound (IIb) mixture under alkaline conditions, and separating a compound (IIIa) out of the obtained product; (c) carrying out cyclization reaction on the compound (IIIa) in an acidic solution to obtain the compound (IIa); (d) reacting the compound (IIa) and thionyl chloride in an organic solvent under the action of a catalyst to obtain a compound (IV); and (e) carrying out reflux reaction on the compound (IV) in ethanol, and adding ammonia water to react, thereby obtaining the compound (V) 6-bromoisoindolinyl-1-one. The method has the advantages of simple route, controllable conditions and high yield, and can easily implement industrial production. The reaction route of the method is disclosed in the specification.
- -
-
Paragraph 0060-0062; 0065-0066
(2018/01/13)
-
- Isomerically Pure Tetramethylrhodamine Voltage Reporters
-
We present the design, synthesis, and application of a new family of fluorescent voltage indicators based on isomerically pure tetramethylrhodamines. These new Rhodamine Voltage Reporters, or RhoVRs, use photoinduced electron transfer (PeT) as a trigger for voltage sensing, display excitation and emission profiles in the green to orange region of the visible spectrum, demonstrate high sensitivity to membrane potential changes (up to 47% ΔF/F per 100 mV), and employ a tertiary amide derived from sarcosine, which aids in membrane localization and simultaneously simplifies the synthetic route to the voltage sensors. The most sensitive of the RhoVR dyes, RhoVR 1, features a methoxy-substituted diethylaniline donor and phenylenevinylene molecular wire at the 5′-position of the rhodamine aryl ring, exhibits the highest voltage sensitivity to date for red-shifted PeT-based voltage sensors, and is compatible with simultaneous imaging alongside green fluorescent protein-based indicators. The discoveries that sarcosine-based tertiary amides in the context of molecular-wire voltage indicators prevent dye internalization and 5′-substituted voltage indicators exhibit improved voltage sensitivity should be broadly applicable to other types of PeT-based voltage-sensitive fluorophores.
- Deal, Parker E.,Kulkarni, Rishikesh U.,Al-Abdullatif, Sarah H.,Miller, Evan W.
-
supporting information
p. 9085 - 9088
(2016/08/05)
-
- Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
-
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
- -
-
Paragraph 1265
(2015/09/22)
-
- Discovery of potent indenoisoquinoline topoisomerase i poisons lacking the 3-nitro toxicophore
-
3-Nitroindenoisoquinoline human topoisomerase IB (Top1) poisons have potent antiproliferative effects on cancer cells. The undesirable nitro toxicophore could hypothetically be replaced by other functional groups that would retain the desired biological activities and minimize potential safety risks. Eleven series of indenoisoquinolines bearing 3-nitro bioisosteres were synthesized. The molecules were evaluated in the Top1-mediated DNA cleavage assay and in the National Cancer Institute's 60 cell line cytotoxicity assay. The data reveal that fluorine and chlorine may substitute for the 3-nitro group with minimal loss of Top1 poisoning activity. The new information gained from these efforts can be used to design novel indenoisoquinolines with improved safety.
- Beck, Daniel E.,Abdelmalak, Monica,Lv, Wei,Reddy, P. V. Narasimha,Tender, Gabrielle S.,O'Neill, Elizaveta,Agama, Keli,Marchand, Christophe,Pommier, Yves,Cushman, Mark
-
p. 3997 - 4015
(2015/05/27)
-
- Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery
-
Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases. Building on the previous identification of NEU-617 (1) as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, we describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors' biological activities against these parasites. In doing this, we have identified several potent proliferation inhibitors for each pathogen, such as 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile (NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.
- Devine, William,Woodring, Jennifer L.,Swaminathan, Uma,Amata, Emanuele,Patel, Gautam,Erath, Jessey,Roncal, Norma E.,Lee, Patricia J.,Leed, Susan E.,Rodriguez, Ana,Mensa-Wilmot, Kojo,Sciotti, Richard J.,Pollastri, Michael P.
-
p. 5522 - 5537
(2015/08/03)
-
- PROTOZOAN PARASITE GROWTH INHIBITORS
-
Compounds and methods for inhibiting growth of a protozoan parasite. Methods of treating a protozoan parasite infection in a subject by administering a therapeutically effective amount of a compound as disclosed herein. The compounds and methods can be us
- -
-
Paragraph 0195
(2015/11/10)
-
- Hypervalent iodine catalyzed cyclization of aryl-substituted alkanoic acids
-
A novel and efficient procedure was developed for direct preparation of aryl-substituted lactones from corresponding aryl-substituted alkanoic acids, catalyzed by the in situ generated hypervalent iodine intermediate from iodobenzene (PhI). In this protocol, aryl-substituted alkanoic acids were treated with m-chloroperbenzoic acid (mCPBA) and KBr in the presence of a catalytic amount of PhI in 2,2,2-trifluoroethanol at room temperature for 24 h, resulting in corresponding aryl lactones in moderate-to-good yields. Copyright
- Li, Tingting,Xiang, Changbin,Zhang, Bijun,Yan, Jie
-
p. 854 - 860
(2014/07/07)
-
- Dehydrogenative lactonization of diols in aqueous media catalyzed by a water-soluble iridium complex bearing a functional bipyridine ligand
-
A new catalytic system for the dehydrogenative lactonization of a variety of benzylic and aliphatic diols in aqueous media was developed. By using a water-soluble, dicationic iridium catalyst bearing 6,6′-dihydroxy-2, 2′-bipyridine as a functional ligand, highly atom economical and environmentally benign synthesis of various lactones was achieved in good to excellent yields. Recovery and reuse of the catalyst were also accomplished by a simple phase separation and the recovered catalyst maintained its high activity at least until the fifth run. Copyright
- Fujita, Ken-Ichi,Ito, Wataru,Yamaguchi, Ryohei
-
p. 109 - 112
(2014/01/23)
-
- Facile organocatalytic domino oxidation of diols to lactones by in situ-generated TetMe-IBX
-
The domino oxidation of diols to lactones is an important transformation, and catalytic protocols that allow this conversion smoothly are scarce. Capitalizing on the established reactivity of tetramethyl-IBX (TetMe-IBX) and its in situ generation in the presence of a co-oxidant, such as oxone, we have shown that a variety of diols can be converted to the corresponding lactones in respectable yields by employing the precursor of TetMe-IBX, namely, tetramethyl-o-iodobenzoic acid (TetMe-IA), as a catalyst in 5 mol % in the presence of 2 equiv of oxone.
- Jhulki, Samik,Seth, Saona,Mondal, Manas,Moorthy, Jarugu Narasimha
-
p. 2286 - 2293
(2014/03/21)
-
- Catalytic and chemoselective oxidation of activated alcohols and direct conversion of diols to lactones with in situ-generated bis-IBX catalyst
-
The twisted 3,3′-diiodo-2,2′,6,6′-tetramethoxybiphenyl-4, 4′-dicarboxylic acid (DIDA) was designed and synthesized for the in situ generation of Bis-IBX and catalytic oxidations. The seemingly better solubility of the in situ-generated Bis-IBX and the attenuated reactivity arising from its unique structural features and methoxy substituents allowed the catalytic oxidation of activated alcohols selectively using DIDA/oxone. Chemoselective oxidations were demonstrated for substrates containing two different hydroxy groups. Furthermore, the unique reactivity of DIDA was demonstrated for sequential oxidation reactions of 1,4- and 1,6-diols to give lactones catalytically in respectable yields.
- Seth, Saona,Jhulki, Samik,Moorthy, Jarugu Narasimha
-
p. 2445 - 2452
(2013/05/22)
-
- A synthetic route to chiral C(3)-functionalized phthalides via a Ag(I)-catalyzed allylation/transesterification sequence
-
A Ag(I)-catalyzed synthesis of chiral C(3)-substituted phthalides (8a-f) via a Sakurai-Hosomi allylation/transesterification reaction is described (ee ≤86%). A notable feature of this reaction is that it utilizes ortho-substituted aldehydes, which are a class of compounds that generally afford poor levels of stereoinduction when applying most known catalytic asymmetric allylation approaches. It was also found that elongation of the n-alkyl chain length (R1, up to n=6; R2=H) of the starting alkyl 2-formylbenzoates (7g-i) improved the enantiomeric excess (ee) of the product.
- Mirabdolbaghi, Roya,Dudding, Travis
-
p. 3287 - 3292
(2013/04/24)
-
- An indium-mediated allylative/transesterification DFT-directed approach to chiral C(3)-functionalized phthalides
-
A one-pot synthesis of chiral C(3)-substituted phthalides via an indium-mediated allylation/transesterification reaction is described. The development of this reaction was facilitated through the applied use of DFT calculations to rationalize the stereoselection of a chiral In-mediated process. It was discovered that the enantiomeric excess of this reaction depended upon the steric size, chain length, and substitution of the aldehyde employed.
- Mirabdolbaghi, Roya,Dudding, Travis
-
supporting information; experimental part
p. 3748 - 3751
(2012/09/07)
-
- SULPHONE COMPOUNDS AND METHODS OF MAKING AND USING SAME
-
The invention provides sulphone compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making various sulphone compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2
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-
Page/Page column 151
(2011/04/26)
-
- COMPOSITIONS FOR TREATMENT OF CYSTIC FIBROSIS AND OTHER CHRONIC DISEASES
-
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
- -
-
-
- Synthesis of isothiocoumarin derivatives
-
A method was developed for the synthesis of 1-oxo-1H-isothiochromenes from 2-benzofuran-1(3H)-one (phthalide). 3-Bromo-6-chloro- and 3,6-dibromo-2- benzofuran-1(3H)-ones were prepared by the bromination of 6-chloro- and 6-bromo-2-benzofuran-1(3H)-ones and were converted by hydrolysis into 5-chloro- or 5-bromo-2-formylbenzoic acids. The condensation of these acids with rhodanine followed by recyclization gave 7-chloro- and 7-bromo-1-oxo-1H-isothiochromene- 3-carboxylic acids.
- Pokhodylo,Matiychuk,Obushak
-
experimental part
p. 140 - 145
(2011/08/07)
-
- Synthesis and biological activity of n-butylphthalide derivatives
-
A series of n-butylphthalide derivatives were designed and synthesized. The in vitro activities of these compounds were evaluated by a resting tension of isolated rat thoracic aorta ring assay. Compounds 4g and 4i were found to be more active than n-butylphthalide.
- Wang, Wei,Cha, Xue-Xiang,Reiner, John,Gao, Yuan,Qiao, Hai-Ling,Shen, Jia-Xiang,Chang, Jun-Biao
-
experimental part
p. 1941 - 1946
(2010/06/19)
-
- PENTACYCLINE COMPOUNDS
-
The present invention is directed to a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (I) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (I) and its therapeutic use.
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-
Page/Page column 50-51
(2010/12/17)
-
- Modulators of ATP-binding cassette transporters
-
Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using compounds of the present invention.
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-
Page/Page column 410
(2008/06/13)
-
- Furan ring opening - Isocoumarine ring closure: A recyclization reaction of 2-carboxyaryldifurylmethanes
-
A general method for the synthesis of isocoumarine derivatives has been developed. Bis(5-R-2-furyl)methylbenzoic acids (R = methyl, ethyl) underwent recyclization and subsequent cyclization into tetracyclic isochromene-1-one derivatives under treatment with hydrogen chloride in methanol. It has been shown that intermediate 4-(5-R-furan-2-yl)-3-(3-oxo-3-R-propyl)-isochromene-1- ones can be obtained selectively by varying a concentration of the hydrogen chloride and reaction times. In the case of R = tert-butyl only corresponding 4-[5-(tert-butyl)-2-furyl]-3-(4,4-dimethyl-3-oxopentyl)-1-isochromenones were isolated regardless of the reaction conditions.
- Abaev, Vladimir T.,Dmitriev, Artem S.,Gutnov, Andrey V.,Podelyakin, Sergey A.,Butin, Alexander V.
-
p. 1195 - 1204
(2007/10/03)
-
- PIPERAZINYLPHENALKYL LACTAM/AMINE LIGANDS FOR THE 5HT1B RECEPTOR
-
The present invention relates to novel derivatives, that are compounds of Formula (I), wherein R1, R2, R3, R14, X, Y, n and m are defined herein, their pharmaceutically acceptable salts, pharmaceutical compositions and methods using said compounds in treating or preventing depression, anxiety, obsessive compulsive disorder (OCD) and other disorders for which selective antagonists, inverse agonists and partial agonists of serotonin 1 (5-HT1) receptors, specifically, antagonists of 5-HT1B are useful.
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Page/Page column 70-71
(2010/11/30)
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- SELECTIVE ESTROGEN RECEPTOR MODULATORS
-
The present invention relates to a selective estrogen receptor modulators of formula I (I); or a pharmaceutical acid addition salt thereof; and of formula II (II); or a pharmaceutical salt thereof; useful, e.g., for treating endometriosis and/or uterine leiomyoma/leiomyomata.
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Page/Page column 29-30
(2010/02/13)
-
- PROCESS FOR THE PREPARATION OF 5-BROMOPHTHALIDE
-
A process, which comprises reducing 4-bromophthalic anhydride in an organic solvent, to obtain a mixture of 5-bromophthalide and 6-bromophthalide, acidifying the reaction mixture, separating the same into aqueous and organic phases, and selectively crystallizing 5-bromophthalide from the organic phase.
- -
-
Page 7; 16-17
(2008/06/13)
-
- WATER-SOLUBLE TRIAZOLE FUNGICIDE
-
A triazole compound of the general formula (I) or a pharmacologically acceptable salt thereof: [wherein,X represents a group of formula X-OH which has antifungal activity,L represents a -(adjacently substituted C6-C10 aryl)-CH2-group and the like, andR represents a -P(=O) (OH)2 group and the like.
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-
Page/Page column 159
(2010/02/07)
-