- Construction of Enantiopure Taxoid and Natural Product-like Scaffolds Using a C-C Bond Cleavage/Arylation Reaction
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An approach to construct enantiopure complex natural product-like frameworks, including the first reported synthesis of a C17 oxygenated taxoid scaffold, is presented. A palladium-catalyzed C-C activation/cross-coupling is utilized to access these structu
- Weber, Manuel,Owens, Kyle,Masarwa, Ahmad,Sarpong, Richmond
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Read Online
- Fungal-Selective Resorcylate Aminopyrazole Hsp90 Inhibitors: Optimization of Whole-Cell Anticryptococcal Activity and Insights into the Structural Origins of Cryptococcal Selectivity
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The essential eukaryotic chaperone Hsp90 regulates the form and function of diverse client proteins, many of which govern thermotolerance, virulence, and drug resistance in fungal species. However, use of Hsp90 inhibitors as antifungal therapeutics has be
- Marcyk, Paul T.,Leblanc, Emmanuelle V.,Kuntz, Douglas A.,Xue, Alice,Ortiz, Francisco,Trilles, Richard,Bengtson, Stephen,Kenney, Tristan M. G.,Huang, David S.,Robbins, Nicole,Williams, Noelle S.,Krysan, Damian J.,Privé, Gilbert G.,Whitesell, Luke,Cowen, Leah E.,Brown, Lauren E.
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p. 1139 - 1169
(2021/02/01)
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- Reinvestigating the acyl cyclization to the precursor of diptoindonesin G
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We reinvestigated the synthesis of the precursor of diptoindonesin G (2) by the intramolecular acyl cyclization of compound 1 or compound 3 in the presence of trifluoroacetic anhydride (TFAA) [1,2]. Although the reaction of 3 with TFAA generated 2 smoothl
- Li, Nan-Sheng,Greene, Geoffrey L.
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supporting information
(2021/03/29)
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- Method for preparing apabetalone, intermediates and preparation method of intermediates
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The invention provides a preparation method of apabetalone. The preparation method comprises the step of reacting a first intermediate, namely 2-bromo-4,6-dimethoxybenzoic acid with a second intermediate, namely 4-(2-hydroxyethoxy)-3,5-dimethylbenzamidine hydrochloride in an alkali-containing organic solvent under the action of a catalyst so as to obtain apabetalone. According to the invention, total yield is 33.4% or above, raw materials are easy to obtain, process is simple, reaction conditions are mild, post-treatment method is simple, the yield of each step and the total yield are high, and cost can be reduced. Apabetalone is a medicine for treating cardiovascular diseases such as atherosclerosis and the like, and has good application prospects. The invention also provides the intermediate 4-(2-hydroxyethoxy)-3,5-dimethylbenzamidine hydrochloride for synthesizing apabetalone and a preparation method thereof, and a preparation method of the compound 2-bromo-4,6-dimethoxybenzoic acid.
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Paragraph 0061-0066
(2020/05/30)
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- AROMATIC DERIVATIVES, PREPARATION METHODS, AND MEDICAL USES THEREOF
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The present disclosure relates generally to aromatic derivatives that are inhibitors of FGFR4 and are useful in treating FGFR4-associated diseases or conditions. Compositions containing the compounds of the present disclosure are also provided.
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Paragraph 0192
(2020/09/19)
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- Synthesis and pharmacological evaluation of childinin E and several derivatives as anti-hyphal formation inhibitors against Candida albicans
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The natural highly substituted benzophenone childinin E (1) was previously isolated from the fungus Daldinia childiae. Here we describe the total synthesis of childinin E and several derivatives using a linear seven-step sequence. The antifungal propertie
- Hirata, Momoka,Kamauchi, Hitoshi,Sugita, Yoshiaki,Takao, Koichi
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supporting information
(2020/11/12)
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- HSP90 INHIBITORS AND USES THEREOF
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Herein is described the design and synthesis of resorcylate aminopyrazole compounds. These compounds show broad, potent and fungal-selective Hsp90 inhibitory activity. These compounds also find use in treating Hsp90 related deseases.
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Paragraph 00476-00478
(2020/11/23)
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- Design and Synthesis of Metabolically Stable tRNA Synthetase Inhibitors Derived from Cladosporin
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Selective and specific inhibitors of Plasmodium falciparum lysyl-tRNA synthetase represent promising therapeutic antimalarial avenues. Cladosporin was identified as a potent P. falciparum lysyl-tRNA synthetase inhibitor, with an activity against parasite
- Rusch, Marion,Thevenon, Arnaud,Hoepfner, Dominic,Aust, Thomas,Studer, Christian,Patoor, Maude,Rollin, Patrick,Livendahl, Madeleine,Ranieri, Beatrice,Schmitt, Esther,Spanka, Carsten,Gademann, Karl,Bouchez, Laure C.
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p. 644 - 649
(2019/02/13)
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- Convergent synthesis of diptoindonesin G
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A convergent and scalable synthetic route to a tetracyclic oligostilbenoid natural product, diptoindonesin G, is described where Suzuki-Miyaura cross-coupling and intramolecular Friedel-Crafts acylation were employed to construct the central C ring of dip
- Singh, Dileep Kumar,Kim, Ikyon
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supporting information
p. 300 - 301
(2019/01/04)
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- Drug compound for treating hepatopathy and application thereof
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The invention discloses a drug compound for treating hepatopathy and application thereof. The drug compound specifically serves as a compound shown in general formula (I) or an optical isomer or a pharmaceutically-acceptable salt of the compound. The compound or the optical isomer or the pharmaceutically-acceptable salt of the compound has a good curative effect and low toxicity on hepatopathy, especially fatty liver. Experiments show that the compound has an obvious protective effect on zebrafish nonalcoholic fatty liver, so that the drug compound has a good application prospect in medicinesfor treatment or prevention of hepatopathy, especially fatty liver or liver fibrosis or liver cirrhosis.
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Paragraph 0307-0309
(2019/10/15)
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- A New Secondary Metabolite from Alternaria Alternata: Structure Elucidation and Total Synthesis of Altenuic Acid IV
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A putative intermediate in the biosynthesis of altenuic acids I–III was isolated from Alternaria alternata in the 1950ies and a sample survived over the decades. This resorcylic lactone named altenuic acid IV is a composite of a resorcylic and a muconic a
- Kohler, Dominik,Podlech, Joachim
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p. 1748 - 1753
(2019/02/20)
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- A novel selenoflavone compound as anti-obesity agent
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The present invention relates to a process for producing a novel selenoflavone compound and a pharmaceutical composition for preventing or treating obesity comprising the selenoflavone compound. In the present invention, selenoflavone, especially PMSF, which has never been synthesized due to synthetic difficulties can be synthesized through palladium-catalyzed direct C-H arylation. Since the synthesized selenoflavone has an improving effect related to activation of brown adipose tissue (BAT), the selenoflavone can be used in the composition for prevention and treatment of obesity.COPYRIGHT KIPO 2018
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Paragraph 0177; 0181; 0207; 0218-0220; 0222
(2018/12/01)
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- Synthesis and Biological Evaluation of Cajaninstilbene Acid and Amorfrutins A and B as Inhibitors of the Pseudomonas aeruginosa Quorum Sensing System
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The quorum sensing (QS) system inhibitors of Pseudomonas aeruginosa are thought to attenuate bacterial pathogenicity and drug resistance by inhibiting biofilm formation and the production of virulence factors. In this study, a synthetic approach to the na
- Xu, Xing-Jun,Zeng, Ting,Huang, Zhi-Xing,Xu, Xiao-Fang,Lin, Jing,Chen, Wei-Min
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p. 2621 - 2629
(2018/11/27)
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- Preparation method for Apabetalone
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The invention relates to a preparation method for Apabetalone, and particularly discloses a synthesis method for Apabetalone. The preparation method comprises the following steps: (1) a first intermediate, i.e., 2-bromo-4,6-dimethoxy benzamide, is prepared; (2) a second intermediate, i.e., 4-{2-[(t-butyldimethylsilicon)oxy]ethyoxyl}-3,5-dimethyl benzaldehyde, is prepared; (3) the first intermediate and the second intermediate are sealed under the conditions of cuprous bromide, cesium carbonate, L-proline and ammonia hydroxide to react, so that Apabetalone is obtained. The preparation method disclosed by the invention is simple, and yield is high.
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Paragraph 0051; 0052
(2018/07/30)
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- Efficient synthesis of polymethoxyselenoflavones via regioselective direct C-H arylation of selenochromones
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Substantial research has suggested that the configuration and the total number of functional groups on flavones influence their bioactivity. To investigate the changes in the biological activities of selenoflavones in relationship to structural changes, the development of a generally applicable synthetic method was a key. Until now, an efficient pathway for palladium-catalyzed direct arylation with the selenocyclic enone systems is not known in the literature. We herein introduce a simple direct C-H arylation of two difficult coupling partners, selenochromones and electron-rich aryl bromide, affording diverse polymethoxyselenoflavones with great efficiency and high selectivity.
- Yang, Woo-Ram,Choi, Yong-Sung,Jeong, Jin-Hyun
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supporting information
p. 3074 - 3083
(2017/04/10)
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- Total Synthesis of the Resorcyclic Acid Lactone Spiroketal Citreoviranol
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The first total synthesis of resorcyclic acid lactone spiroketal citreoviranol (1) is described. The synthesis was completed in nine steps and via Sonogashira cross-coupling, gold-catalyzed cyclization, and an unusual base-induced ketalization. The relati
- Quach, Rachelle,Furkert, Daniel. P.,Brimble, Margaret A.
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p. 8343 - 8350
(2016/09/28)
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- HETEROARYL COMPOUNDS AND USES THEREOF
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The present invention relates to compounds useful as inhibitors of protein kinases, containing a cysteine residue in the ATP binding site. The invention further provides for pharmaceutically acceptable compositions comprising therapeutically effective amounts of one or more of the protein kinase inhibitor compounds and methods of using said compositions in the treatment of cancers and carcinomas.
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Paragraph 00838
(2014/09/29)
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- Increasing the structural span of alkyne metathesis
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A new generation of alkyne metathesis catalysts, which are distinguished by high activity and an exquisite functional group tolerance, allows the scope of this transformation to be extended beyond its traditional range. They accept substrates that were previously found problematic or unreactive, such as propargyl alcohol derivatives, electron-deficient and electron-rich acetylenes of various types, and even terminal alkynes. Moreover, post-metathetic transformations other than semi-reduction increase the structural portfolio, as witnessed by the synthesis of a annulated phenol derivative via ring-closing alkyne metathesis (RCAM) followed by a transannular gold-catalyzed Conia-ene reaction. Further examples encompass a post-metathetic transannular ketone-alkyne cyclization with formation of a trisubstituted furan, a ruthenium-catalyzed redox isomerization, and a Meyer-Schuster rearrangement/oxa-Michael cascade. These reaction modes fueled model studies toward salicylate macrolides, furanocembranolides, and the cytotoxic macrolides acutiphycin and enigmazole A; moreover, they served as the key design elements of concise total syntheses of dehydrocurvularin (27) and the antibiotic agent A26771B (36). Ask for more! Many possibilities exist to take advantage of alkyne metathesis. In addition to the approved semi-reduction to stereodefined olefins, it is shown how to convert the products primarily formed into aromatic or heteroaromatic rings, enones, Michael adducts, or β-ketolactones. At the same time, new types of substrates were engaged, including electron-rich, electron-poor, and terminal alkynes, as well as propargyl alcohol derivatives. Copyright
- Persich, Peter,Llaveria, Josep,Lhermet, Rudy,Deharo, Teresa,Stade, Robert,Kondoh, Azusa,Fuerstner, Alois
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p. 13047 - 13058
(2013/10/01)
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- Catalytic asymmetric total synthesis of (S)-(-)-zearalenone, a novel lipoxygenase inhibitor
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A catalytic asymmetric synthesis of (S)-(-)-zearalenone is reported using asymmetric allylic alkylation for the introduction of the stereocenter. (S)-(-)-Zearalenone turned out to be a novel lipoxygenase inhibitor.
- Baggelaar, Marc P.,Huang, Yange,Feringa, Ben L.,Dekker, Frank J.,Minnaard, Adriaan J.
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p. 5271 - 5274
(2013/09/02)
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- SYNTHESIS OF THE POTENT IMMUNOSUPPRESSANT AGENTS DALESCONOL A AND B
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This invention relates to compounds having the structure: wherein bonds α, β, γ, δ, ω, η, χ, ε, κ, and μ are each present or absent, and R1-R18 are various substituents described herein.
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Page/Page column 7; 61-62
(2011/09/19)
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- TRISUBSTITUTED BORON-CONTAINING MOLECULES
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This invention largely relates to 3,4,6-trisubstituted benzoxaborole compounds, and their use for treating bacterial infections.
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Page/Page column 124
(2011/02/24)
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- Total syntheses of dalesconol A and B
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(Chemical equation Presented) (Chemical equation Presented) A polycyclic collapse: Use of a carefully designed acyclic intermediate participated in a cascade reaction that formed the entire core of the polyketide-derived dalesconols in a single flask (see scheme). A number of additional and carefully controlled synthetic operations completed an expeditious synthesis of both of these highly bioactive natural products as well as structural congenors.
- Snyder, Scott A.,Sherwood, Trevor C.,Ross, Audrey G.
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supporting information; experimental part
p. 5146 - 5150
(2010/11/04)
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- COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASES
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The present disclosure relates to compounds, which are useful for regulating the expression of apolipoprotein A-I (ApoA-I), and their use for treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis.
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Page/Page column 31-32
(2008/12/07)
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- A new mechanism for benzopyrone formation in aromatic polyketide biosynthesis
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Aromatic polyketides are all biosynthesized from highly reactive poly-β-ketone intermediates. Keys to introducing the vast chemical diversity seen in these natural products are the enzymatic and non-enzymatic tailoring chemistries that occur after biosynt
- Zhang, Wenjun,Wilke, Burkhardt I.,Zhan, Jixun,Watanabe, Kenji,Boddy, Christopher N.,Tang, Yi
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p. 9304 - 9305
(2008/02/10)
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- Depsidone Synthesis. Part 21. A New Synthesis of Grisa-2',5'-diene-3,4'-diones
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Treatment of suitably substituted methyl 2-phenoxybenzoates with titanium(IV) chloride and dry hydrogen chloride afforded grisa-2',5'-diene-3,4'-diones in high yield.The structures of these compounds followed from their thermal stability, their methanolysis to methyl 2-(4-hydroxyphenoxy)benzoates, and their reductive cleavage to 2,4'-dihydrobenzophenones.Treatment of the benzophenones with base gave xanthones.An attempt to synthesize dehydrogriseofulvin (1) by this method failed.
- Sargent, Melvyn V.
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p. 403 - 411
(2007/10/02)
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