- Radical Carbonyl Propargylation by Dual Catalysis
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Carbonyl propargylation has been established as a valuable tool in the realm of carbon–carbon bond forming reactions. The 1,3-enyne moiety has been recognized as an alternative pronucleophile in the above transformation through an ionic mechanism. Herein, we report for the first time, the radical carbonyl propargylation through dual chromium/photoredox catalysis. A library of valuable homopropargylic alcohols bearing all-carbon quaternary centers could be obtained by a catalytic radical three-component coupling of 1,3-enynes, aldehydes and suitable radical precursors (41 examples). This redox-neutral multi-component reaction occurs under very mild conditions and shows high functional group tolerance. Remarkably, bench-stable, non-toxic, and inexpensive CrCl3 could be employed as a chromium source. Preliminary mechanistic investigations suggest a radical-polar crossover mechanism, which offers a complementary and novel approach towards the preparation of valuable synthetic architectures from simple chemicals.
- Huang, Huan-Ming,Bellotti, Peter,Daniliuc, Constantin G.,Glorius, Frank
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supporting information
p. 2464 - 2471
(2020/12/07)
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- Synthesis of the analogs of plocabulin and their preliminary structure-activity relationship study
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Plocabulin, a marine natural polyketide isolated from the sponge Lithoplocamia lithistoides, is a novel and potent microtubule-destabilizing agent. Guided by the reported binding mode, several new analogs of plocabulin have been designed through removing
- Wang, Leiming,Li, Xin,Cui, Hong,Lei, Xinsheng,Liu, Hongchun,Wang, Quanrui,Li, Yingxia
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supporting information
(2021/09/28)
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- Facile preparation of 2-aryl-3-iodopyrroles with N-tosyl 4-aryl-3-butyn-1-ylamines, I2, andtBuOK
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Treatment of N-tosyl 4-aryl-3-butyn-1-ylamines with I2 and K2CO3, followed by the reaction withtBuOK under mild conditions gave 2-aryl-3-iodopyrroles in good yields. The present approach is a one-pot method for the preparation of 2-aryl-3-iodopyrroles from N-tosyl 4-aryl-3-butyn-1-ylamines, which could be easily prepared from aryl iodides, N-(3-butyn-1-yl)phthalimides, and p-toluenesulfonyl chloride.
- Naruto, Hiroki,Shibasaki, Kaho,Togo, Hideo
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p. 1091 - 1118
(2021/06/21)
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- Regio- And stereoselective electrochemical synthesis of sulfonylated enethers from alkynes and sulfonyl hydrazides
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An electrooxidative direct difunctionalization of internal alkynes with sulfonyl hydrazides has been developed for the construction of sulfonated enethers. In this transformation, metal catalysts or stoichiometric amount of oxidants are not required and molecular nitrogen and hydrogen are the sole byproducts, providing a simple and green approach for preparing various sulfonyl tetrasubstituted alkenes. Notably, the protocol could be efficiently scaled up and the follow-up procedures of the corresponding functionalized alkenes demonstrate the practicality of the electrochemical synthesis.
- Du, Wu-Bo,Wang, Ning-Ning,Pan, Chao,Ni, Shao-Fei,Wen, Li-Rong,Li, Ming,Zhang, Lin-Bao
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supporting information
p. 2420 - 2426
(2021/04/07)
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- Design, synthesis and structure-activity relationships of novel 15-membered macrolides: Quinolone/quinoline-containing sidechains tethered to the C-6 position of azithromycin acylides
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In the search for novel hybrid molecules by fusing two biologically active scaffolds into one heteromeric chemotype, we found that hybrids of azithromycin and ciprofloxacin/gatifloxacin 26j and 26l can inhibit the supercoiling activity of E. coli gyrase by poisoning it in a way similar to fluoroquinolones. This may modestly contribute to their potencies, which are equal to ciprofloxacin against constitutively resistant Staphylococcus aureus, whose growth is not inhibited by the presence of macrolides. In contrast, introduction of quinolines (the 3-quinoline 26b and the 6-quinoline 26o) with an optimized rigid spacer at the 6-OH of azithromycin acylides did not exert significant potency against constitutively resistant S. aureus, despite the fact that the quinoline-containing compounds, exemplified by 26o, were as active as telithromycin against susceptible, inducibly- and efflux-resistant pathogens. The novel dual modes of action involving protein synthesis inhibition and poisoning DNA replication may pave the way for restoration of antibacterial activities of the current macrolides against constitutively resistant clinical isolates.
- Aldrich, Courtney,Brody, Scott,Cushman, Mark,Fan, Bing-Zhi,Hiasa, Hiroshi,Liang, Jian-Hua,Lv, Wei,Yang, Zhao-Yong
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- 17BETA-HETEROCYCLYL-DIGITALIS LIKE COMPOUNDS FOR THE TREATMENT OF HEART FAILURE
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Disclosed are compounds of formula (I) wherein X, Y, Z are annular atoms comprised in a five-membered carbocyclic or heterocyclic ring, selected from the group consisting of CH, NH, N, O, S; said carbocyclic or heterocyclic ring being optionally substituted with amino (C1-C4) linear or branched alkyl or guanidine or guanidino (C1-C4) linear or branched alkyl; with the proviso that the heterocycle ring is not furyl; n is 0 or 1; R is H or OH; the dotted line represents an optional double bond C=C; the thick line represents a bond in the β configuration; the wavy line represents a bond both in the α and β configuration; their enantiomeric and/or diastereomeric mixtures, their pharmaceutically acceptable salts, their solvates, hydrates; their metabolite and metabolic precursors. The compounds of formula (I) are for use as medicaments, in particular for the treatment of acute or chronic heart failure. Oral administration is also possible.
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Page/Page column 0215; 0217; 0218
(2020/02/13)
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- MACROCYCLE CONTAINING AMINOPYRAZOLE AND PYRIMIDINE AND PHARMACEUTICAL COMPOSITION AND USE THEREOF
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The present application relates to a macrocycle containing aminopyrazole and pyrimidine, which is represented by formula (I), a pharmaceutical composition thereof, and a use thereof in inhibiting tropomyosin receptor kinase (Trk) activity and in treating diseases in mammals that are mediated by Trk.
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Paragraph 0077-0078
(2020/07/15)
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- Synthesis of Exo- and Endocyclic Enamides Through Copper-Catalyzed Regioselective Intramolecular N-Halovinylation
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Cross-couplings between amides and 1,2-dihaloalkenes are an efficient and straightforward way to access β-haloenamides which, in turn, can be functionalized into complex, stereodefined enamide motifs. However, the intramolecular version of these cross-couplings, leading to cyclic β-haloenamides, has not been formally studied. In this paper, we report an investigation of factors affecting the efficiency of the reaction and its selectivity between potential exo and endo cyclization products. We demonstrate that exo/endo selectivity is largely determined by ring strain, whether it arises from the size of the resulting ring or from the structure of the starting compound, but that selectivity can also be modulated by varying reaction conditions. Finally, we show that resulting β-haloenamides readily undergo transition metal-catalyzed reactions, making this sequence a viable way to access highly functionalized cyclic enamides.
- Bergeron, Jodrey,Daoust, Benoit,Gilbert, Nicolas,Lambolez, Pierre,Ricard, Simon
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supporting information
(2020/05/04)
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- Method for synthesizing alkyne through catalytic asymmetric cross coupling (by machine translation)
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The invention belongs to the field of, asymmetric synthesis, and discloses a method for catalyzing asymmetric cross- coupling to synthesize: an alkyne, and the L method comprises, the following steps, of A: preparing B a cuprous, salt and C a: ligand; preparing a catalyst; adding a base; reacting the compound with the compound with the compound; and reacting the compound with the compound. Of these, one of them, X is selected from the group consisting of, R halogens. 1 Optionally substituted heteroarylsulfonylcyanamide groups selected from the, group consisting, of optionally substituted, phenyl groups In-flight vehicle, R6 Trialkyl silyl groups or alkyl radicals, R2 Cycloalkyl radicals optionally substituted with an, optionally substituted alkyl, (CH radical2 )n R4 Multi,layer chain, n＝0-10,R saw blade4 A group selected, from, the group consisting of phenyl, alkenyl, aralkynyls, noonyloxy,and, noonylsulfonylsulfonylsulfonylsulfonylsulfonylsulfonylsulfonylsulfonylsulfonylsulphonylsulphonylsulphonylsulphonylsulphonylsulphonylsulphonylsulphonylsulphonylsulphonylphenyl disiloxy-radicals. R3 A ligand, selected from hydrogen or any of the functional groups, is selected from the group consisting of, hydrogen and any L other functional group. The method, R disclosed by the, A invention has the, advantages of good catalytic, R ’ effect, wide application range. and high catalytic efficiency, and the, method disclosed by the, invention has the. advantages of good catalytic effect, wide application range and high catalytic efficiency. (by machine translation)
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Paragraph 0171; 0193-0195
(2020/01/12)
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- Discovery of a New Isoxazole-3-hydroxamate-Based Histone Deacetylase 6 Inhibitor SS-208 with Antitumor Activity in Syngeneic Melanoma Mouse Models
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Isoxazole is a five-membered heterocycle that is widely used in drug discovery endeavors. Here, we report the design, synthesis, and structural and biological characterization of SS-208, a novel HDAC6-selective inhibitor containing the isoxazole-3-hydroxamate moiety as a zinc-binding group as well as a hydrophobic linker. A crystal structure of the Danio rerio HDAC6/SS-208 complex reveals a bidentate coordination of the active-site zinc ion that differs from the preferred monodentate coordination observed for HDAC6 complexes with phenylhydroxamate-based inhibitors. While SS-208 has minimal effects on the viability of murine SM1 melanoma cells in vitro, it significantly reduced in vivo tumor growth in a murine SM1 syngeneic melanoma mouse model. These findings suggest that the antitumor activity of SS-208 is mainly mediated by immune-related antitumor activity as evidenced by the increased infiltration of CD8+ and NK+ T cells and the enhanced ratio of M1 and M2 macrophages in the tumor microenvironment.
- Shen, Sida,Hadley, Melissa,Ustinova, Kseniya,Pavlicek, Jiri,Knox, Tessa,Noonepalle, Satish,Tavares, Mauricio T.,Zimprich, Chad A.,Zhang, Guiping,Robers, Matthew B.,Ba?inka, Cyril,Kozikowski, Alan P.,Villagra, Alejandro
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p. 8557 - 8577
(2019/10/02)
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- ISOXAZOLE HYDROXAMIC ACIDS AS HISTONE DEACETYLASE 6 INHIBITORS
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The present disclosure provides compounds represented by Formula (I): (Formula(I) and pharmaceutically acceptable salts, solvates, e.g., hydrates, and prodrugs thereof, wherein X and n are as defined as set forth in the specification. The present disclosure also provides compounds of Formula (I) for use to treat diseases and conditions, e.g., cancer, wherein inhibition of HDAC provides a benefit.
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Paragraph 0243; 0247; 0251; 0255
(2018/10/25)
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- Hydration and Intramolecular Cyclization of Homopropargyl Sulfonamide Derivatives Catalyzed by Silver Hexafluoroantimonate(V): Synthesis of Structurally Diverse 2,3-Dihydro-1H-Pyrroles
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We have developed an efficient, simple protocol for synthesis of structurally diverse functionalized 2,3-dihydro-1H-pyrroles by hydration and intramolecular cyclization of homopropargyl sulfonamide derivatives. Mechanistic experiments revealed that the sulfonamide nitrogen participated in the hydration reaction by chelating the Ag atom of the catalyst to assist in the formation of the hydration intermediate. The protocol accommodated a wide range of substrates and was used for a formal synthesis of (S)-nicotine. (Figure presented.).
- Yu, Xiuling,Guo, Zhonglin,Song, Hongjian,Liu, Yuxiu,Wang, Qingmin
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p. 1077 - 1081
(2018/01/22)
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- Transformation of Carbonyl Compounds into Homologous Alkynes under Neutral Conditions: Fragmentation of Tetrazoles Derived from Cyanophosphates
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Cyanophosphates (CPs) can be easily prepared from either ketones or aldehydes, and their reaction with NaN3-Et3N·HCl results in the formation of azidotetrazoles. Under microwave irradiation, successive fragmentation of the azidotetrazoles generates alkylidene carbenes that undergo [1,2]-rearrangement and are transformed into homologous alkynes. Treatment of ketone-derived CPs with TMSN3 and Bu2SnO as catalyst in toluene at reflux directly yields the corresponding internal alkynes, whereas the reaction of aldehyde-derived CPs with NaN3-Et3N·HCl in THF at reflux or TMSN3-Bu2SnO (cat.) in toluene at reflux provides homologous terminal alkynes in good yields. These reactions take place under neutral conditions and can be successfully extended to obtain alkynes that are not usually accessible from the corresponding carbonyl compounds by the Ohira-Bestmann or Shioiri procedures, which require basic conditions.
- Yoneyama, Hiroki,Numata, Masahiro,Uemura, Kenji,Usami, Yoshihide,Harusawa, Shinya
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p. 5538 - 5556
(2017/06/07)
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- Synthesis and antimicrobial evaluation of cationic low molecular weight amphipathic 1,2,3-triazoles
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A library of 28 small cationic 1,4-substituted 1,2,3-triazoles was prepared for studies of antimicrobial activity. The structures addressed the pharmacophore model of small antimicrobial peptides and an amphipathic motif found in marine antimicrobials. Eight compounds showed promising antimicrobial activity, of which the most potent compound 10b displayed minimum inhibitory concentrations of 4–8?μg/mL against Streptococcus agalacticae, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis. The simple syntheses and low degree of functionalization make these 1,4-substituted 1,2,3-triazoles interesting for further optimizations.
- Bakka, Thomas A.,Str?m, Morten B.,Andersen, Jeanette H.,Gautun, Odd R.
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supporting information
p. 1119 - 1123
(2017/06/21)
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- Radical Cation Cycloadditions Using Cleavable Redox Auxiliaries
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The incorporation of an easily oxidized arylsulfide moiety facilitates the photocatalytic generation of alkene radical cations that undergo a variety of cycloaddition reactions with electron-rich reaction partners. The sulfide moiety can subsequently be reductively cleaved in a traceless fashion, affording products that are not otherwise directly accessible using photoredox catalysis. This approach constitutes a novel oxidative “redox auxiliary” strategy that offers a practical means to circumvent a fundamental thermodynamic limitation facing photoredox reactions.
- Lin, Shishi,Lies, Shane D.,Gravatt, Christopher S.,Yoon, Tehshik P.
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supporting information
p. 368 - 371
(2017/04/21)
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- Facile one-pot synthesis of 2,3-dihydro-1H-indolizinium derivatives by rhodium(iii)-catalyzed intramolecular oxidative annulation via C-H activation: application to ficuseptine synthesis
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Various substituted indolizidinium, quinolizinium and pyrido[1,2-a]azepinium salts synthesized from benzaldehydes (or α,β-unsaturated aldehydes) and alkyne-amines catalyzed by rhodium complexes via C-H activation are demonstrated. The reaction was carried
- Upadhyay, Nitinkumar Satyadev,Jayakumar, Jayachandran,Cheng, Chien-Hong
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supporting information
p. 2491 - 2494
(2017/03/01)
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- FUSED RING HETEROARYL COMPOUNDS AND THEIR USE AS TRK INHIBITORS
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The disclosure provides novel chemical compounds represented by Formula I or a pharmaceutically acceptable salt, solvate, polymorph, ester, tautomer or prodrug thereof. The compounds can be used as an inhibitor of Trk and are useful in the treatment of pain, cancer, inflammation, neurodegenerative disease and certain infectious diseases. In some compounds of Formula I, Q is —CH═CR3C(O)NR4R5, —C≡CC(O)NR4R5, or
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Paragraph 0183; 0185; 0186
(2016/07/05)
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- Regioselective Amine–Borane Cyclization: Towards the Synthesis of 1,2-BN-3-Cyclohexene by Copper-Assisted Triazole/Gold Catalysis
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The combination of triazole/gold (TA-Au) and Cu(OTf)2is identified as the optimal catalytic system for promoting intramolecular hydroboration for the synthesis of a six-membered cyclic amine–borane. Excellent yields (up to 95 %) and regioselectivities (5-exo vs. 6-endo) were achieved through catalyst control and sequential dilution. Good functional-group tolerance was attained, thus allowing the preparation of highly functionalized cyclic amine–borane substrates, which could not be achieved using other methods. Deuterium-labeling studies support the involvement of a hydride addition to a gold-activated alkyne with subsequent C?B bond formation.
- Motika, Stephen E.,Wang, Qiaoyi,Akhmedov, Novruz G.,Wojtas, Lukasz,Shi, Xiaodong
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supporting information
p. 11582 - 11586
(2016/10/24)
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- Modular, Concise, and Efficient Synthesis of Highly Functionalized 5-Fluoropyridazines by a [2 + 1]/[3 + 2]-Cycloaddition Sequence
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An easy access to 5-fluoropyridazines by a [2 + 1]/[3 + 2]-cycloaddition sequence between terminal alkynes, a difluorocarbene, and a diazo compound is reported. This approach does not necessitate the isolation of any intermediates, and a wide range of novel 5-fluoropyridazines was synthesized from readily available starting materials. Additionally, these compounds were used as a platform to access novel and highly diversified pyridazines.
- Tran, Ga?l,Gomez Pardo, Domingo,Tsuchiya, Tomoki,Hillebrand, Stefan,Vors, Jean-Pierre,Cossy, Janine
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supporting information
p. 3414 - 3417
(2015/07/28)
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- Palladium-catalysed cyclisation of N-alkynyl aminomalonates
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Go around in (hetero)cycles! The palladium-catalysed tandem cyclisation/coupling reaction of alkynyl- and alkenyl-substituted aminomalonates leads to highly functionalised pyrrolidines and piperidines in good yield (see scheme). The reaction allows efficient access to a broad range of synthetically valuable building blocks.
- Hess, Wilfried,Burton, Jonathan W.
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supporting information; experimental part
p. 12303 - 12306
(2011/02/23)
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- Processes for the preparation of N-substituted phthalimides
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The present invention describes a process for preparing N-substituted phthalimides of Formula I which are widely useful as intermediates in the preparation of organic compounds such as pharmaceuticals.
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Page/Page column 4
(2008/06/13)
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- Recognition of CG inversions in DNA triple helices by methylated 3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one nucleoside analogues
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Substituted 3H-pyrrolo[2,3-d]pyrimidin-2(7H)-one nucleoside analogues have been synthesised from 5-alkynyl-uridine derivatives, incorporated into triplex forming oligonucleotides (TFOs) and found to selectively bind CG inversions with enhanced affinity co
- Ranasinghe, Rohan T.,Rusling, David A.,Powers, Vicki E. C.,Fox, Keith R.,Brown, Tom
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p. 2555 - 2557
(2007/10/03)
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- Synthesis of substituted Se-phenyl selenocarboxylates from terminal alkynes
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Se-Phenyl selenocarboxylates have been conveniently prepared from (phenylseleno)acetylenes by treatment with p-toluenesulfonic acid monohydrate in dichloromethane. This easy conversion is compatible with a broad range of oxygen- and nitrogen-containing functional groups. The Se-phenyl selenocarboxylates were easily converted into the corresponding esters and amides. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Tiecco, Marcello,Testaferri, Lorenzo,Temperini, Andrea,Bagnoli, Luana,Marini, Francesca,Santi, Claudio,Terlizzi, Raffaella
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p. 3447 - 3458
(2007/10/03)
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- PYRIDYL SUBSTITUTED KETOLIDE ANTIBIOTICS
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Antimicrobial macrolide and ketolide compounds are provided having formulas (XII), as well as pharmaceutically acceptable salts, esters or prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.
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- Pyridoarylphenyl oxazolidinone antibacterials, and related compositions and methods
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Pyridoarylphenyl oxazolidinone compounds of the formula: in which the substituents have the meaning indicated in the description. These compounds are useful as antibacterial agents.
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- Prodrugs activated by targeted catalytic proteins
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Prodrugs that are activated by and conjugated to a catalytic antibody conjugated to a moiety that binds to a tumor cell population are provided.
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- Model studies for damage to nucleic acids mediated by thiyl radicals
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The ability of phenylthiovinyl radicals to abstract hydrogen from appropriately substituted carbon atoms has been studied as a model for the reactions of the deoxyribose units of DNA with similar radicals in two.
- Griffiths,Murphy
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p. 5543 - 5556
(2007/10/02)
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- The Stereochemistry of Organometallic Compounds. XXXII. Hydrocyanation of Derivatives of Amino Alkynes
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The hydrocyanation of a range of amino alkyne derivatives has been studied by using nickel-based catalyst systems.The phthalimido derivatives have been shown to give good yields of unsaturated cyano amine derivatives, and some of these have been converted into both saturated and unsaturated amino acids.
- Jackson, W. Roy,Perlmutter, Patrick,Smallridge, Andrew J.
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p. 1201 - 1208
(2007/10/02)
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- THE HYDROCYANATION ROUTE TO β- AND γ-AMINO ACIDS. A SYNTHESIS OF α-METHYLENE-β-ALANINE
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Hydrocyanation of several phthalimidoalkynes proceeds with good regioselection yielding products which were easily converted into unsaturated β- and γ-amino acids.
- Jackson, W. Roy,Perlmutter, Patrick,Smallridge, Andrew
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p. 1983 - 1984
(2007/10/02)
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- Fibrin stabilizing factor inhibitors. 12. 5 dibenzylaminopentylamine and related compounds, a new type of FSF inhibitors
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A series of omega dibenzylaminoalkylamines and related compounds have been prepared and tested as inhibitors of fibrin cross linking. This structural type was chosen in an attempt to develop noncompetitive inhibitors of fibrinoligase. By the combination o
- Hoffmann,Stenberg,Ljunggren,Svensson,Nilsson
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p. 278 - 284
(2007/10/04)
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