- Cobalt(ii)-catalyzed benzylic oxidations with potassium persulfate in TFA/TFAA
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A cobalt-catalyzed C(sp3)-H oxygenation reaction to furnish aldehyde was herein reported. This transformation demonstrated high chemo-selectivity, and tolerated various methylarenes bearing electron-withdrawing substituents. This reaction provided rapid access to diverse aldehydes form methylarenes. Notably, TFA/TFAA was used for the first time as a mixed solvent in cobalt-catalyzed oxygenation of benzylic methylenes.
- Li, Tianlei,Li, Jishun,Zhu, Zihao,Pan, Weidong,Wu, Song
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p. 20879 - 20883
(2019/07/12)
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- Design, synthesis and biological evaluation of anti-pancreatic cancer activity of plinabulin derivatives based on the co-crystal structure
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Based on the co-crystal structures of tubulin with plinabulin and Compound 1 (a derivative of plinabulin), a total of 18 novel plinabulin derivatives were designed and synthesized. Their biological activities were evaluated against human pancreatic cancer BxPC-3 cell lines. Two novel Compounds 13d and 13e exhibited potent activities with IC50 at 1.56 and 1.72 nM, respectively. The tubulin polymerization assay indicated that these derivatives could inhibit microtubule polymerization. Furthermore, the interaction between tubulin and these compounds were elucidated by molecular docking. The binding modes of Compounds 13d and 13e were similar to the co-crystal structure of Compound 1. H-π interaction was observed between the aromatic hydrogen of thiophene moiety with Phe20, which could enhance their binding affinities.
- Fu, Zhangyu,Hou, Yingwei,Ji, Cunpeng,Ma, Mingxu,Tian, Zhenhua,Deng, Mengyan,Zhong, Lili,Chu, Yanyan,Li, Wenbao
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p. 2061 - 2072
(2018/03/26)
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- CO2-Catalyzed oxidation of benzylic and allylic alcohols with DMSO
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CO2-catalyzed transition-metal-free oxidation of alcohols has been achieved. Earlier, several methodologies have been explored for alcohol oxidations based on transition-metal catalysts. However, owing to the cheaper price, easy separation and nontoxicity, transition-metal-free systems are in high demand to the pharmaceutical industries. For this reason, various primary and secondary alcohols have been selectively oxidized to the corresponding carbonyl compounds using CO2 as a catalyst in the presence of different functional groups such as nitrile, nitro, aldehyde, ester, halogen, ether, and so on. At the end, transition-metal-free syntheses of pharmaceuticals have also been achieved. Finally, the role of CO2 has been investigated in detail, and the mechanism is proposed on the basis of experiments and DFT calculations.
- Riemer, Daniel,Mandaviya, Bhavdip,Schilling, Waldemar,G?tz, Anne Charlotte,Kühl, Torben,Finger, Markus,Das, Shoubhik
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p. 3030 - 3034
(2018/04/14)
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- Deuteration dehydrogenation 3-benzoyl phenyl plinabulin compound, preparation method of compound and application of compound to preparation of anti-tumor medicine
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The invention provides a deuteration dehydrogenation 3-benzoyl phenyl plinabulin compound, a preparation method of the compound and application of the compound to preparation of anti-tumor medicine. The compound has the structure shown by the general formula (I). A synthesis method comprises the following steps that firstly, diacetyl piperazinedione and deuterium aldehyde compounds b take a condensation reaction to form a deuterium heterocyclic ring containing compound c; then, a condensation reaction is taken with 3-benzoyl benzaldehyde compounds to form the deuteration dehydrogenation 3-benzoyl phenyl plinabulin compound. Meanwhile, the invention also provides an efficient high-deuteration-rate deuterium aldehyde intermediate and a deuterium heterocyclic ring containing the intermediate and a synthesis method thereof, and also provides an efficient synthesis method of the deuteration dehydrogenation 3-benzoyl phenyl plinabulin compound at the same time. Experiments prove that the deuteration dehydrogenation 3-benzoyl phenyl plinabulin compound provided by the invention has the effect of inhibiting the pancreatic cancer growth. The invention provides a method for studying and developing the anti-pancreatic cancer medicine relevant to the related compound.
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Paragraph 0097; 0098; 0099; 0100; 0101
(2017/10/31)
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- Reactions of difunctional electrophiles with functionalized aryllithium compounds: Remarkable chemoselectivity by flash chemistry
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Flash chemistry using flow microreactors enables highly chemoselective reactions of difunctional electrophiles with functionalized aryllithium compounds by virtue of extremely fast micromixing. The approach serves as a powerful method for protecting-group-free synthesis using organolithium compounds and opens a new possibility in the synthesis of polyfunctional organic molecules.
- Nagaki, Aiichiro,Imai, Keita,Ishiuchi, Satoshi,Yoshida, Jun-Ichi
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supporting information
p. 1914 - 1918
(2015/02/19)
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- Development of a Rhodium(II)-Catalyzed Chemoselective C(sp3)-H Oxygenation
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We report the first example of RhII-catalyzed chemoselective double C(sp3)-H oxygenation, which can directly transform various toluene derivatives into highly valuable aromatic aldehydes with great chemoselectivity and practicality. The critical combination of catalyst Rh(OAc)2, oxidant Selectfluor, and solvents of TFA/TFAA promises the successful delivery of the oxidation with satisfactory yields. A possible mechanism involving a unique carbene-Rh complex is proposed, and has been supported by both experiments and theoretical calculations.
- Lin, Yun,Zhu, Lei,Lan, Yu,Rao, Yu
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supporting information
p. 14937 - 14942
(2015/10/19)
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- Unmasked acyl anion equivalent from acid chloride with indium: Reversed-polarity synthesis of unsymmetric aryl aryl and alkenyl aryl ketone through palladium-catalyzed cross-coupling reaction
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A reversed-polarity synthetic method of a range of unsymmetric aryl aryl and alkenyl aryl ketones has been developed through Pd-catalyzed cross-coupling reaction of acylindium reagents generated in situ from easily available acid chlorides and indium with various electrophiles such as aryl iodide and triflate and alkenyl triflate.
- Lee, Dohyung,Ryu, Taekyu,Park, Youngchul,Lee, Phil Ho
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supporting information
p. 1144 - 1147
(2014/03/21)
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- Design and synthesis of l- and d-phenylalanine derived rhodanines with novel C5-arylidenes as inhibitors of HCV NS5B polymerase
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Hepatitis C virus (HCV) NS5B polymerase is a key target for anti-HCV therapeutics development. Herein, we report the synthesis and in vitro evaluation of anti-NS5B polymerase activity of a molecular hybrid of our previously reported lead compounds 1 (IC50 = 7.7 μM) and 2 (IC50 = 10.6 μM) as represented by hybrid compound 27 (IC 50 = 6.7 μM). We have explored the optimal substituents on the terminal phenyl ring of the 3-phenoxybenzylidene moiety in 27, by generating a set of six analogs. This resulted in the identification of compound 34 with an IC50 of 2.6 μM. To probe the role of stereochemistry towards the observed biological activity, we synthesized and evaluated the d-isomers 41 (IC50 = 19.3 μM) and 45 (IC50 = 5.4 μM) as enantiomers of the l-isomers 27 and 34, respectively. The binding site of compounds 32 and 34 was mapped to palm pocket-I (PP-I) of NS5B. The docking models of 34 and 45 within the PP-I of NS5B were investigated to envisage the molecular mechanism of inhibition.
- Patel, Bhargav A.,Krishnan, Ramalingam,Khadtare, Nikhil,Gurukumar,Basu, Amartya,Arora, Payal,Bhatt, Aaditya,Patel, Maulik R.,Dana, Dibyendu,Kumar, Sanjai,Kaushik-Basu, Neerja,Talele, Tanaji T.
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p. 3262 - 3271
(2013/07/05)
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- Tubulin photoaffinity labeling study with a plinabulin chemical probe possessing a biotin tag at the oxazole
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A new bioactive photoaffinity probe KPU-252-B1 (4) possessing a biotin tag on the oxazole ring of a potent plinabulin derivative KPU-244 (2) was synthesized via the CuI-catalyzed Huisgen's cycloaddition reaction to understand the precise binding mode of the diketopiperazine-based anti-microtubule agent plinabulin on tubulin. Probe 4 showed significant binding affinity toward tubulin and cytotoxicity against an HT-29 cells. A photoaffinity labeling study suggested that probe 4 specifically recognizes tubulin at a binding site that binds plinabulin or colchicine, most likely near or at the colchicine binding site, which is located at the interfacial region formed by α-and β-tubulin association. The results also demonstrated that probe 4 may serve as a useful plinabulin chemical probe to investigate the molecular mechanism by which anti-microtubule diketopiperazine derivatives operate.
- Yamazaki, Yuri,Kido, Yui,Hidaka, Koushi,Yasui, Hiroyuki,Kiso, Yoshiaki,Yakushiji, Fumika,Hayashi, Yoshio
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experimental part
p. 595 - 602
(2011/03/17)
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- Reaction mechanisms and structural characterization of the reactive intermediates observed after the photolysis of 3-(hydroxymethyl)benzophenone in acetonitrile, 2-propanol, and neutral and acidic aqueous solutions
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Nanosecond time-resolved resonance Raman (ns-TR3) spectroscopy was employed to investigate the photoinduced reactions of 3-(hydroxymethyl) benzophenone (1) in acetonitrile, 2-propanol, and neutral and acidic aqueous solutions. Density functional theory calculations were utilized to help the interpretation of the experimental spectra. In acetonitrile, the neutral triplet state 1 [denoted here as (m-BPOH)3] was observed on the nanosecond to microsecond time scale. In 2-propanol this triplet state appeared to abstract a hydrogen atom from the solvent molecules to produce the aryphenyl ketyl radical of 1 (denoted here as ArPK of 1), and then this species underwent a cross-coupling reaction with the dimethylketyl radical (also formed from the hydrogen abstraction reaction) to form a long-lived light absorbing transient species that was tentatively identified to be mainly 2-(4-(hydroxy(3- (hydroxymethyl)phenyl)methylene)cyclohexa-2,5-dienyl)propan-2-ol. In 1:1 H 2O:CH3CN aqueous solution at neutral pH, (m-BPOH) 3 reacted with water to produce the ArPK of 1 and then underwent further reaction to produce a long-lived light absorbing transient species. Three photochemical reactions appeared to take place after 266 nm photolysis of 1 in acidic aqueous solutions, a photoreduction reaction, an overall photohydration reaction, and a novel photoredox reaction. TR3 experiments in 1:1 H2O:CH3CN aqueous solution at pH 2 detected a new triplet biradical species, which is associated with an unusual photoredox reaction. This reaction is observed to be the predominant reaction at pH 2 and seems to face competition from the overall photohydration reaction at pH 0.
- Ma, Jiani,Li, Ming-De,Phillips, David Lee,Wan, Peter
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supporting information; scheme or table
p. 3710 - 3719
(2011/06/22)
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- Inhibitors of phenylalanine ammonia-lyase: Substituted derivatives of 2-aminoindane-2-phosphonic acid and 1-aminobenzylphosphonic acid
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Six derivatives of 2-aminoindane-2-phosphonic acid and 1-aminobenzylphosphonic acid were synthesized. The compounds were tested both as inhibitors of buckwheat phenylalanine ammonia-lyase (in vitro) and as inhibitors of anthocyanin biosynthesis (in vivo). (±)-2-Amino-4-bromoindane-2-phosphonic acid was found to be the strongest inhibitor from investigated compounds. The results obtained are a basis for design of phenylalanine ammonia-lyase inhibitors useful in the enzyme structure studies in photo labelling experiments.
- Miziak, Piotr,Zon, Jerzy,Amrhein, Nikolaus,Gancarz, Roman
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p. 407 - 415
(2007/10/03)
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- Substituent effects in the intramolecular photoredox reactions of benzophenones in aqueous solution
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A number of α-hydroxy-3-benzylbenzophenones 7-11 have been synthesized for the purpose of studying the effect of a phenyl substituent on the intramolecular photoredox reaction of 3-(hydroxymethyl)benzophenone (5) discovered in our laboratory. This latter compound was found to undergo a unimolecular (formal) intramolecular redox reaction upon photolysis in aqueous acid that results in clean reduction of the benzophenone ketone (to secondary alcohol) and oxidation of the alcohol to aldehyde. Three of the phenyl-substituted compounds with simple phenyl (7), p-methylphenyl (8), and p-methoxyphenyl (9) were found to undergo the acid-catalyzed intramolecular photoredox reaction with the observation that 9 also undergoes a residual photoredox reaction that is not acid-mediated and may in-volve initial photoinduced electron transfer, which is supported by LFP data. The m-methoxyphenyl (10) compound did not undergo the reaction. The trend in observed relative reactivity may be partially rationalized by examining changes in molecular orbital coefficients observed in the calculated HOMOs and LUMOs. The photoredox reaction has also been applied twice in succession in a single compound 11, demonstrating that the photoredox reaction may be useful for sequential photoredox reactions in a multifunctional compound.
- Basaric, Nikola,Mitchell, Devin,Wan, Peter
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p. 561 - 571
(2008/02/12)
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- Catalyst-free oxidation of alcohols at room temperature using water as solvent
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An effective, cheap, environmentally benign and catalyst-free oxidation of alcohols was carried out at room temperature using tetra-n-butylammonium Oxone (TBA-OX) as oxidant with moderate to high selectivity for most of the alcohols using water as the solvent.
- Lei, Ziqiang,Yang, Yaoxia,Bai, Xiangzhen
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p. 877 - 880
(2007/10/03)
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- Design, synthesis, and biological evaluation of potent discodermolide fluorescent and photoaffinity molecular probes
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(Chemical Equation Presented) The design, synthesis, and biological evaluation of a series of (+)-discodermolide molecular probes possessing photoaffinity and fluorescent appendages has been achieved. Stereoselective olefin cross-metathesis comprised a ke
- Smith III, Amos B.,Rucker, Paul V.,Brouard, Ignacio,Freeze, B. Scott,Xia, Shujun,Horwitz, Susan Band
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p. 5199 - 5202
(2007/10/03)
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- Formal intramolecular photoredox chemistry of meta-substituted benzophenones
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(Chemical Equation Presented) Photolysis of 3-(hydroxymethyl)benzophenone (1) in aqueous solution (pH -4 M) conditions. Evidence suggests that the highly efficient (Φ ~ 0.6) reaction involves a unimolecular mechanism and an overall formal intramolecular photoredox process, which requires electronic communication between the 1,3-positions of the benzene ring, an unprecedented example of the photochemical meta effect. The photoredox reaction was not observed in organic solvents, where only photoreduction of the benzophenone moiety was observed.
- Mitchell, Devin,Lukeman, Matthew,Lehnherr, Dan,Wan, Peter
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p. 3387 - 3389
(2007/10/03)
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- Trisubstituted-N-[(1S)-1,2,3,4-tetrahydro-1-naphthalenyl] benzamides which inhibit P2X3 and P2X2/3 containing receptors
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Compounds of formula (I) are novel P2X3 and P2X2/P2X3 antagonists which are useful in treating pain, urinary incontinence and bladder overactivity.
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- Fluorenone and benzophenone 1,4-dihydropyridine derivatives with cardiodepressant activity
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A series of fluorenone and benzophenone 1,4-dihydropyridine derivatives were prepared. The compounds were evaluated for inotropic, chronotropic and calcium antagonist properties.
- Rampa,Budriesi,Bisi,Chiarini,Valenti
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p. 1284 - 1287
(2007/10/02)
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- SUBSTITUTED-4-THIAZOLIDINONE DERIVATIVES
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Disclosed are novel substituted 4-thiazolidinone derivatives having cyclooxygenase and 5-lipoxygenase inhibiting properties and which are topical antiinflammatory agents for inflammed conditions of the skin
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- Pesticides
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New pesticidal e.g. insecticidal, compounds are of formula STR1 wherein X represents hydrogen, halogeno or an alkyl group, Z represents hydrogen, an alkyl group or a cyano or ethynyl group and R represents the residue of a carboxylic acid RCOOH which is a
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- Pesticides
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New insecticides are of formula: STR1 wherein R1 represents hydrogen or a methyl group; R2 represents hydrogen or a halogeno or lower alkyl group; R3 represents hydrogen or a halogeno or carbo(lower alkoxy) group which contains at least 2 carbon atoms in the lower alkoxy residue when R2 represents methyl; with the proviso that (a) R2 and R3 each represent hydrogen only when R1 represents methyl, (b) when R1 and R3 each represent hydrogen and R2 represents alkyl, that alkyl group contains at least 2 carbon atoms and (c) when R3 represents halogeno, R2 represents hydrogen or halogeno; and R represents a group which forms insecticidal esters with chrysanthemic acid e.g. 5-benzyl-3-furylmethyl, 3-phenoxybenzyl, α-cyano-3-phenoxybenzyl. The esters are prepared by forming the ester linkage conventionally or by a Wittig reaction using a 3-formyl- or 3-acetyl-2,2-dimethyl cyclopropane carboxylic acid esterified with the desired residue or by an alkyl group which is subsequently converted to the desired residue.
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