- Synthesis of Methyl (5Z,9Z,17R)-17-Methylnonadeca-5,9-dienoate, the (R)-Enantiomer of the Structure Proposed for a Metabolite of the Philippine Sponge Plakinastrella sp.
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The (R)-enantiomer (1) of methyl (5Z,9Z)-17-methylnonadeca-5,9-dienoate, the structure proposed for a metabolite of the Philippine sponge, Plakinastrella sp., was synthesized. The 1H- and 13C-NMR spectra of the synthetic material were different from those reported for the natural product. The proposed structure 1 is therefore incorrect.
- Takagi, Miho,Takikawa, Hirosato,Mori, Kenji
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- Mitochondria-Targeted Lupane Triterpenoid Derivatives and Their Selective Apoptosis-Inducing Anticancer Mechanisms
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Betulin and betulinic acid have been widely studied for their anticancer activities. However, their further development is limited due to low bioavailability, poor aqueous solubility, and limited intracellular accumulation. In the present study, a triphenylphosphonium cation moiety was linked to betulin and betulinic acid to specifically target them to cancer cell mitochondria. Biological characterization established that uptake of mitochondria-targeted compound 1a in the mitochondria of cancer cells was increased compared to betulin. The mitochondria-targeted derivatives of betulin and betulinic acid showed stronger cytotoxicity than their parent drugs and exhibited more cytotoxic effects in cancer cells than normal cells. The mechanisms may involve the mitochondrial apoptotic pathway, probably caused by the induction of reactive oxygen species production and reducing mitochondrial membrane potential. More importantly, 1a significantly inhibited cancer cell proliferation and migration in an in vivo zebrafish xenograft model. Collectively, these results encourage further study of 1a analogs as anticancer agents.
- Ye, Yaqing,Zhang, Tao,Yuan, Huiqing,Li, Defeng,Lou, Hongxiang,Fan, Peihong
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- Synthesis and Kinetic Studies of a Simple Prostacyclin Model
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A simple prostacyclin model, (Z)-6,9-epoxynon-5-enoic acid, has been synthesized, and the rate of hydrolysis of the vinyl ether functional group of it and its methyl ester has been measured by monitoring UV spectral changes over the pH range 1-8 at 25.0 +/- 0.1 deg C and total ionic strength 0.1 M.The measurements show that (Z)-6,9-epoxynon-5-enoic acid is 82 times more reactive than its methyl ester at high pH when the carboxylic acid group is in an ionized form.The present results indicate that the simple model closely mimics the behavior of prostacyclin.
- Bergman, Nils-Ake,Jansson, Marie,Chiang, Yvonne,Kresge, A. Jerry,Yin, Ya
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- Rational design of mitochondria-targeted pyruvate dehydrogenase kinase 1 inhibitors with improved selectivity and antiproliferative activity
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Herein, triphenylphosphonium cation moieties were incorporated into a dichloroacetophenone derivative, leading to the discovery of novel mitochondria-targeted and tumor-specific pyruvate dehydrogenase kinase 1 (PDK1) inhibitors. Biological studies suggest
- Xu, Biao,Yu, Zhimei,Xiang, Sichuan,Li, Yunshan,Zhang, Shao-Lin,He, Yun
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- Convenient approach for the synthesis of ONO-LB-457, a potent leukotriene B4 receptor antagonist
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This study reports a new approach for the synthesis of 5-[2-(2-carboxyethyl)-3-[6-(4-methoxyphenyl)-(5E)-hexen-1-yloxy]phenoxy]pentanoic acid V (ONO-LB-457), previously described by Konno and col. and which is considered a highly potent and orally active
- Hamri, Salha,Jouha, Jabrane,Oumessaoud, Asmaa,Pujol,Khouili, Mostafa,Guillaumet, Gérald
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- Binding and action of triphenylphosphonium analog of chloramphenicol upon the bacterial ribosome
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Chloramphenicol (CHL) is a ribosome-targeting antibiotic that binds to the peptidyl transferase center (PTC) of the bacterial ribosome and inhibits peptide bond formation. As an approach for modifying and potentially improving the properties of this inhib
- Chen, Chih-Wei,Pavlova, Julia A.,Lukianov, Dmitrii A.,Tereshchenkov, Andrey G.,Makarov, Gennady I.,Khairullina, Zimfira Z.,Tashlitsky, Vadim N.,Paleskava, Alena,Konevega, Andrey L.,Bogdanov, Alexey A.,Osterman, Ilya A.,Sumbatyan, Natalia V.,Polikanov, Yury S.
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- A mitochondrial targeting of the nano drug delivery system and its preparation method and application
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The invention discloses a mitochondrion-targeting nano-drug delivery system, comprising polyethylene glycol connected with TPP and thioketal linker connected with a chemotherapeutic drug, the polyethylene glycol and the thioketal linker are connected with
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Paragraph 0046; 0062-0063
(2019/04/18)
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- Impact of Mitochondrion-Targeting Group on the Reactivity and Cytostatic Pathway of Platinum(IV) Complexes
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Platinum(IV) complexes are prodrugs of cisplatin with multiple potential advantages over platinum(II) drugs. Mitochondria play pivotal roles in producing energy and inducing death of cancer cells. Two platinum(IV) complexes, namely, c,c,t-[Pt(NH3)2Cl2(OH)(OCOCH2CH2CH2CH2PPh3)]Br and c,c,t-[Pt(NH3)2Cl2(OCOCH2CH2CH2CH2PPh3)2]Br2, were designed to explore the effect of mitochondrion-targeting group(s) on the bioactivity and cytotoxicity of platinum(IV) complexes. The complexes were characterized by electrospray ionization mass spectrometry, reverse-phase high-performance liquid chromatography, and multinuclear (1H, 13C, 31P, and 195Pt) NMR spectroscopy. The introduction of triphenylphosphonium targeting group(s) markedly influences the reactivity and cytotoxicity of the Pt(IV) complexes. The targeted complex displays more potent disruptive effect on mitochondria but less inhibitory effect on cancer cells than cisplatin. The lipophilicity of the Pt(IV) complexes is enhanced by the targeting group(s), while their reactivity to DNA is decreased. As a result, the mitochondrial morphology and adenosine triphosphate producing ability are impaired, which constitutes an alternative pathway to inhibit cancer cells. This study shows that both the reactivity of platinum(IV) center and the property of axial targeting ligand exert influences on the cytotoxicity of targeted Pt(IV) complexes. For targeting groups with pharmacological activities, their intrinsic function could enrich the anticancer mechanism of Pt(IV) complexes.
- Jin, Suxing,Hao, Yigang,Zhu, Zhenzhu,Muhammad, Nafees,Zhang, Zhenqin,Wang, Kun,Guo, Yan,Guo, Zijian,Wang, Xiaoyong
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p. 11135 - 11145
(2018/09/14)
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- Quaternary phosphonium salt modified dendritic polymer preparation and application of
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The invention belongs to the technical field of biological materials, and particularly relates to preparation and application of a quaternary phosphonium salt modified dendriform molecule. The invention provides a quaternary phosphonium salt and a prepara
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Paragraph 0143; 0144; 0145
(2018/01/19)
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- Combination of Lewis Basic Selenium Catalysis and Redox Selenium Chemistry: Synthesis of Trifluoromethylthiolated Tertiary Alcohols with Alkenes
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A new and efficient method for diaryl selenide catalyzed vicinal CF3S hydroxylation of 1,1-multisubstitued alkenes has been developed. Various trifluoromethylthiolated tertiary alcohols could be readily synthesized under mild conditions. This method is also effective for the intramolecular cyclization of alkenes tethered by carboxylic acid, hydroxy, sulfamide, or ester groups and is associated with the introduction of a CF3S group. Mechanistic studies have revealed that the pathway involves a redox cycle between Se(II) and Se(IV) and Lewis basic selenium catalysis.
- Zhu, Zechen,Luo, Jie,Zhao, Xiaodan
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supporting information
p. 4940 - 4943
(2017/09/23)
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- Organoselenium-catalyzed synthesis of oxygen- and nitrogen-containing heterocycles
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A new and efficient approach for the synthesis of oxygen and nitrogen heterocycles by organoselenium catalysis has been developed. The exo-cyclization proceeded smoothly under mild conditions with good functional group tolerance and excellent regioselectivity. Mechanistic studies revealed that 1-fluoropyridinium triflate is key for oxidative cyclization.
- Guo, Ruizhi,Huang, Jiachen,Huang, Haiyan,Zhao, Xiaodan
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supporting information
p. 504 - 507
(2016/02/18)
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- The optically pure sodium alcoholate dextrorotary chlorine forefront of the method for the preparation of
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The invention relates to a preparation method of optically pure dextro cloprostenol sodium. The method comprises the following steps: using the combination of ketonic acid and S-phenylethylamine resolving agent, and carrying out chiral resolution to obtain S-propenylphosphonate with the structural formula of R-ketonic acid; then separating to obtain R-chlorone and preparing to obtain R-cloprostenol sodium. The preparation method has the benefits that the optically pure dextro cloprostenol sodium in the invention is called D-cloprostenol sodium for short, the using amount only needs one third of cloprostenol sodium being a racemic modification in current market, and the pesticide effect is obviously better than cloprostenol sodium with three times of using amount.
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Paragraph 0126 - 0128
(2018/02/04)
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- Synthesis of (±)-15-deoxy-Δ12,14-prostaglandin J2 and Δ12-prostaglandin J2 15-acetate methyl esters
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A new synthetic approach to 15-deoxy-Δ12,14-prostaglandin J2 and related compounds starting from Corey (±)-lactone diol has been developed. The key stage of this approach includes synthesis of a prostaglandin derivative possessing le
- Vostrikov, N. S.,Lobko, I. F.,Miftakhov, M. S.,Ishimova, D. U.
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- Functionalized phosphonium-based ionic liquids as efficient catalysts for the synthesis of cyclic carbonate from expoxides and carbon dioxide
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A series of novel functionalized phosphonium-based ionic liquids (FPBILs) were synthesized by a simple method, and first evaluated as catalysts for the synthesis of cyclic carbonates through the cycloaddition of CO2 to epoxides in the absence of co-catalyst and solvent. The FPBILs perform well in the cycloaddition reaction, especially the carboxyl-functionalized one. Over [Ph3PC2H4COOH]Br, the yield of propylene carbonate is 97.3% (TOF = 64.9 h-1) at 130 C and 2.5 MPa in 3 h. The synergistic effects of polarization induced by hydrogen bonding and nucleophilic attack of Br-anion account for the excellent performance. Furthermore, the FPBILs with moderate methylene chain length show superior catalytic activity. It is because they have both strong acidity and weak electrostatic interaction between phosphonium cation and halide anion. The strong acidity facilitates the ring-opening of epoxyl, and the weak electrostatic interaction enhances the nucleophilic attack capability of Br -. It is envisaged that the metal- and solvent-free process has high potential for the catalytic conversion of CO2 into value-added chemicals.
- Dai, Wei-Li,Jin, Bi,Luo, Sheng-Lian,Luo, Xu-Biao,Tu, Xin-Man,Au, Chak-Tong
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p. 183 - 188
(2014/01/06)
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- A photo-favorskii ring contraction reaction: The effect of ring size
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The effect of ring size on the photo-Favorskii induced ring-contraction reaction of the hydroxybenzocycloalkanonyl acetate and mesylate esters (7a-d, 8a-c) has provided new insight into the mechanism of the rearrangement. By monotonically decreasing the ring size in these cyclic derivatives, the increasing ring strain imposed on the formation of the elusive bicyclic spirocyclopropanone 20 results in a divergence away from rearrangement and toward solvolysis. Cycloalkanones of seven or eight carbons undergo a highly efficient photo-Favorskii rearrangement with ring contraction paralleling the photochemistry of p-hydroxyphenacyl esters. In contrast, the five-carbon ring does not rearrange but is diverted to the photosolvolysis channel avoiding the increased strain energy that would accompany the formation of the spirobicyclic ketone, the "Favorskii intermediate 20". The six-carbon analogue demonstrates the bifurcation in reaction channels, yielding a solvent-sensitive mixture of both. Employing a combination of time-resolved absorption measurements, quantum yield determinations, isotopic labeling, and solvent variation studies coupled with theoretical treatment, a more comprehensive mechanistic description of the rearrangement has emerged.
- Kammath, Viju Balachandran,?olomek, Tomá?,Ngoy, Bokolombe Pitchou,Heger, Dominik,Klán, Petr,Rubina, Marina,Givens, Richard S.
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supporting information
p. 1718 - 1729
(2013/03/29)
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- The manufacture of a homochiral 4-silyloxycyclopentenone intermediate for the synthesis of prostaglandin analogues
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A process is described for the synthesis of kilogram quantities of homochiral 4-silyloxycyclopentenone (R)-1, a key intermediate useful for the synthesis of a plurality of prostaglandin analogue drugs. Cyclopentenone (R)-1 was synthesized in 14 isolated steps from furfural. Key steps in the synthesis include a Wittig reaction, Piancatelli rearrangement, and an enzymatic resolution featuring in situ recycling of the undesired enantiomer furnishing the desired homochiral alcohol in ≥99.5% ee. As a retort to the unsatisfactory coformation of about 8% at best of the trans-olefin in the Wittig reaction, a change to the order of several steps and the identification of a recrystallisable, amine salt derivative, 2, allowed the unwanted isomer to be controlled to as low as 0.2%.
- Henschke, Julian P.,Liu, Yuanlian,Huang, Xiaohong,Chen, Yungfa,Meng, Dechao,Xia, Lizhen,Wei, Xiuqiong,Xie, Aiping,Li, Danhong,Huang, Qiang,Sun, Ting,Wang, Juan,Gu, Xuebin,Huang, Xinyan,Wang, Longhu,Xiao, Jun,Qiu, Shenhai
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p. 1905 - 1916
(2013/03/13)
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- Design, synthesis and antimycobacterial activities of 1-methyl-2-alkenyl- 4(1H)-quinolones
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A series of 23 new 1-methyl-2-alkenyl-4(1H)quinolones have been synthesized and evaluated in vitro for their antimycobacterial activities against fast growing species of mycobacteria, such as Mycobacterium fortuitum, M. smegmatis and M. phlei. The compounds displayed good to excellent inhibition of the growth of the mycobacterial test strains with improved antimycobacterial activity compared to the hit compound, evocarpine. The most active compounds, which possessed chain length of 11-13 carbons at position-2 displayed potent inhibitory effects with an MIC value of 1.0 mg/L. In a human diploid embryonic lung cell line, MRC-5 cytotoxicity assay, the alkaloids showed weak to moderate cytotoxic activity. Biological evaluation of these evocarpine analogues on the less pathogenic fast growing strains of mycobacteria showed an interesting antimycobacterial profile and provided significant insight into the structure-activity relationships.
- Wube, Abraham A.,Hüfner, Antje,Thomaschitz, Christina,Blunder, Martina,Kollroser, Manfred,Bauer, Rudolf,Bucar, Franz
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experimental part
p. 567 - 579
(2011/03/17)
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- Scaffold-based design and synthesis of potent N-type calcium channel blockers
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The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type calcium channel blockers. During this optim
- Zamponi, Gerald W.,Feng, Zhong-Ping,Zhang, Lingyun,Pajouhesh, Hossein,Ding, Yanbing,Belardetti, Francesco,Pajouhesh, Hassan,Dolphin, David,Mitscher, Lester A.,Snutch, Terrance P.
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experimental part
p. 6467 - 6472
(2010/04/30)
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- Novel 1,8-naphthyridin-2(1h)-one derivatives
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The purpose is to provide selective PDE IV inhibitors which have a potent anti-asthmatic profile with excellent safety. A compound of the formula (1): wherein: A is an unsubstituted or optionally substituted 5 or 6 membered heteroaryl group or a fused benzene ring in which any of the above-defined heteroaryl groups is fused to a benzene ring, B is carbon or nitrogen, R1 is hydrogen, lower alkyl, trifluoromethyl, hydroxyl, lower alkoxy, a residue derived from a carboxylic acid or a derivative thereof, amino, or an amino nitrogen-containing group, R2 is hydrogen, halogen, cyano, nitro, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, hydroxyl, lower alkoxy, a residue derived from a carboxylic acid or a derivative thereof, amino, or an amino nitrogen-containing group, and m is an integer of from 1 to 8, both inclusive; or a pharmaceutically acceptable salt thereof possesses selective PDE IV inhibition and is useful as a pharmaceutical drug, preferably an anti-asthmatic, etc.
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- Cyclization of 5-hexenyl radicals from nitroxyl radical additions to 4-pentenylketenes and from the acyloin reaction
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Photochemical Wolff rearrangements were used to form 5-substituted-4-pentenylketenes 1a-1d (RCH=CHCH2X-CH 2CH=C=O: 1a R = H, X = CH2; 1b R = Ph, X = CH 2; 1c R = c-Pr, X = CH2; 1d R = H, X = O), which were observed by IR at 2121, 2120, 2119, and 2126 cm-1, respectively, as relatively long-lived species at room temperature in hydrocarbon solvents. These reacted with the nitroxyl radical tetramethylpiperidinyloxyl (TEMPO, TO·) forming carboxy-substituted 5-hexenyl radicals 3, which were trapped by a second nitroxyl radical forming 1,2 diaddition products 4a-4d. On thermolysis, 4a-4d underwent reversible reformation of the radicals 3, which underwent cyclization forming cyclopentanecarboxylic acid derivatives 6 or 11 as the major products. However, in the case of 1b, the cyclopentane derivative was formed reversibly and on prolonged reaction times the only product isolated was PhCH=CH-(CH2)4CO2H (8b) from hydrogen transfer to Cβ and cleavage of the TEMPO group. Cyclopropylcarbinyl radical ring opening in the cyclized radical 5c from 1c led to the 2-(4-N-tetramethylpiperidinyloxybut-1-enyl)cyclopentane derivative 11 as the major product. In a test for 5-hexenyl radical ring closure in the radical anion intermediate of the acyloin condensation, the ester CH 2=CH(CH2)3CO2Et (12a) gave the acyloin 13a (76%) as the only observed product, while PhCH=CH(CH 2)3CO2CH3 (12b) with Na in toluene gave 21% of the acyloin product 13b and 42% of 2-benzylcyclopentanol (15) from cyclization of the intermediate radical anion.
- Henry-Riyad, Huda,Tidwell, Thomas T.
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p. 697 - 704
(2007/10/03)
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- Difluoroprostaglandin derivatives and their use
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A fluorine-containing prostaglandin derivative of the formula (1) (or a salt thereof) and a medicine containing it, particularly, a preventive or therapeutic medicine for an eye disease: STR1 wherein A is a vinylene group or the like, R1 is an
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- New synthetic strategies to vitamin D analogues modified at the side chain and D ring. Synthesis of 1α,25-dihydroxy-16-ene-vitamin D3 and C-20 analogues
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Two efficient synthetic routes to 1α,25-dihydroxy-16-ene-vitamin D3 (4a) and their C-20 analogues (3 and 4) have been developed. Key features common to both routes A and B are the introduction of side chains functionalized at C20 (17, 21, 19, and 25). In route A the CD side chain fragments 5 and 6 are prepared by SN2' syn displacement of allylic carbamates 8 and 9 (X = OCONHPh) by Li2Cu3R5. The triene unit is then constructed by assembling the latter fragments with the A-ring fragment using the Wittig- Horner method (average yield of vitamin D analogue 35%, 11-13 steps from ketone 11). In route B, the SN2' syn displacement of the carbamate moiety by Li2Cu3R5 is carried out on intermediates 12 and 13, both of which bear the vitamin D triene unit (average yield of vitamin D analogue 27%, 13-15 steps from ketone 11). The latter route is particularly attractive as an approach to diverse C-20 vitamin D analogues for biological screening.
- De Los Angeles Rey, Maria,Martinez-Perez, Jose Antonio,Fernandez-Gacio, Ana,Halkes, Koen,Fall, Yagamare,Granja, Juan,Mourino, Antonio
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p. 3196 - 3206
(2007/10/03)
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- Double Wittig reactions with 4-carboxybutylidene triphenylphosphorane as the key step in the synthesis of benzene derivatives metadisubstituted with ωω'-difunctionalized six-carbon chains
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Using a double Wittig reaction from diformylbenzene derivatives, a direct synthetic way to 1,3-di(5-carboxypent-1-yl)benzene compounds is discussed.
- Provent, Christophe,Chautemps, Pierre,Gellon, Gisele,Pierre, Jean-Louis
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p. 1393 - 1396
(2007/10/03)
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- Novel Ring Cleavage Based on Intermolecular Aldol Condensation
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Ring cleavage and reconstruction via intramolecular aldol condensation followed by Grob fragmentation under acetalization conditions (BF3/ethylene glycol) was developed into a novel ring cleavage based on intermolecular aldol condensation.On the basis of
- Nagumo, Shinji,Matsukuma, Aki,Suemune, Hiroshi,Sakai, Kiyoshi
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p. 10501 - 10510
(2007/10/02)
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- Synthesis and in Vitro Activity of Various Derivatives of a Novel Thromboxane Receptor Antagonist, (+/-)-(5Z)-7-bicyclohept-2-exo-yl>heptenoic Acid
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Several sulfonyl derivatives (13a-t) of (+/-)-(5Z)-7-(3-endo-amonobicyclohept-2-exo-yl)heptenoic acid (VI) were synthesized via its methyl ester 10.Sulfonylation of 10 with 11a-t followed by saponification yielded 13a-t.Inhibitory concentrations (IC50) of the corresponding sodium salts 14a-t for platelet aggregation were measured with rat washed platelets (WP) and rabbit platelet-rich plasma (PRP).IC50 values of some derivatives for contraction of the rat aorta were also measured.The IC50 values for rat WP increased from 2.9 to 26 nM in the order of 14a, 14c, 14d, and 14b for derivatives with an arylsulfonyl residue, depending on the number of interventing methylene groups.Methyl derivative 14e exhibited a higher IC50 value than n-hexyl derivative 14f.Substitution with a p-methyl-, p-fluoro-, or p-chloro group in 14a retained or slightly reduced its IC50 value, while a p-n-pentyl or p-oxycarbonyl group augmented it significantly.The representative 14a supressed (15S)-15-hydroxy-11,9-(epoxymethano)prosta-5(Z),13(E)-dienoic acid (U-46619) induced aggregation of human WP with an IC50 value of 7.7 nM, which corresponds well to the IC50 value of 3 nM obtained for each displacement by 14a of -U-46619 or (5Z,15ξ)-9α,11α-(dimethylmethano)-15-hydroxy-16-(3-iodo-4-hydroxyphenyl)-17,18,19,20-tetranor-13-aza-11a-carbathrombo-5-enoic acid (-PTA-OH) bound to human WP.Synthesis of thromboxane A2 (TxA2) in human WP stimulated by thrombin was not inhibited by 14a at a concentration up to 10 μM.From these observations, the corresponding acid 13a (S-145) was concluded to be potent TxA2 receptor antagonist.
- Narisada, Masayuki,Ohtani, Mitsuaki,Watanabe, Fumihiko,Uchida, Kiyohisa,Arita, Hitoshi,et al.
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p. 1847 - 1854
(2007/10/02)
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- Carbacyclin derivatives
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Carbacyclin derivatives with anti-ulcer activity comprise compounds of the general formula (I): STR1 (wherein R1 is selected from the group consisting of a hydrogen atom and an alkyl group having from 1 to 10 carbon atoms; R2 is sele
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- Thromboxane Synthetase Inhibitors (TXSI). Design, Synthesis, and Evaluation of a Novel Series of ω-Pyridylalkenoic Acids
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A novel series of ω-pyridylalkenoic acids has been prepared by applying the Wittig reaction.Modifications were made in the ω-aryl moiety, the alkylene chain length, the α-methylene group adjacent to the carbonyl group, and the carboxyl group in the molecu
- Kato, Kaneyoshi,Ohkawa, Shigenori,Terao, Shinji,Terashita, Zen-ichi,Nishikawa, Kohei
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p. 287 - 294
(2007/10/02)
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- 16-Methyl prost-5-en-13-ynoic acid derivatives
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16S and 16R methyl 13, 14 dehydro PGE2 compounds have been prepared.
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