- Total Synthesis of (±)-Codonopiloneolignanin A
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An intramolecular formal [3 + 2] cationic cycloaddition between benzylic carbocation and styrene was developed for the total synthesis of codonopiloneolignanin A. Further study shows benzocycloheptene as a good substrate for 1,3-dipolar cycloaddition, and a model study toward cephalocyclidine A skeleton was reported.
- Gao, Zhiyu,Ren, Li,Wang, Ruizhi,Shi, Liang,Wang, Yanhai,Su, Feng,Hao, Hong-Dong
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Read Online
- Synthesis of the 5-hydroxymethyl-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one natural products descurainin and cartorimine
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Reaction of pyranulose 6 with styrenes 12c or 13 and Et3N in CH2Cl2 at 25 °C afforded the [5+2] cycloadducts 14c and 15, which were hydrolyzed to give the natural products 1 and descurainin (2) in 24 and 27% overall yield, respectively. Heating pyranulose 6 with cinnamate ester 21 in the presence of 2,6-di-t-butylpyridine in CH3CN at 175 °C afforded the [5+2] cycloadduct, which was hydrolyzed to give cartorimine (3) in 13% yield.
- Snider, Barry B.,Grabowski, James F.
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- Synthesis and optical properties of polystyrene bearing stilbenoid side chains
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Four series of random graft copolymers with stilbenoid side chains on a polystyrene (PS) backbone were synthesized, and their optical properties were compared with blends of a series of model compounds in PS. The graft loading (5, 15, and 25 mol %), the type of link to the polymer backbone ("ether" or "direct"), and the number of methoxy groups substituted on the stilbene moiety were systematically varied. Absorption, emission, and time-resolved photoluminescence (PL) properties are presented for the compounds in solution and as spin-coated films, and relative quantum yields have been determined. Mixed monomer/excimer emission was found to be the characteristic emission for all grafts, while the reversibility of the excimer formation seems to vary for the different grafts. In the blends the miscibility of the model compounds is quite different: the 4-methoxystilbene/PS system readily forms aggregates and crystallites, whereas the 3,4,5-trimethoxy-4′- methylstilbene/PS system forms uniform mixtures showing excimer-type emission. The PL efficiencies decreased with concentration in all cases where excimeric emission was found. For the blend containing 4-methoxystilbene, however, the PL efficiency increased with concentration.
- Aerts,Wuyts,Dermaut,Goovaerts,Geise,Blockhuys
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Read Online
- Alpha,beta-unsaturated ketone derivatives, preparation method of derivatives and application of derivatives as medicines
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The invention relates to the technical field of medicine, and proposes alpha,beta-unsaturated ketone derivatives and a preparation method thereof. The derivatives have a structural general formula represented by a formula I shown in the specification, whe
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Paragraph 0171-0175
(2019/12/15)
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- 4-AZAPODOPHYLOTOXINS COMPOUNDS
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The present disclosure relates to 4-azapodophylotoxins compounds, pharmaceutical compositions comprising such compounds, kits, and methods for using such compounds or pharmaceutical compositions.
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Page/Page column 70
(2017/09/15)
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- The synthesis and analysis of lignin-bound Hibbert ketone structures in technical lignins
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Understanding the structure of technical lignins resulting from acid-catalysed treatment of lignocellulosic biomass is important for their future applications. Here we report an investigation into the fate of lignin under acidic aqueous organosolv conditions. In particular we examine in detail the formation and reactivity of non-native Hibbert ketone structures found in isolated organosolv lignins from both Douglas fir and beech woods. Through the use of model compounds combined with HSQC, HMBC and HSQC-TOCSY NMR experiments we demonstrate that, depending on the lignin source, both S and G lignin-bound Hibbert ketone units can be present. We also show that these units can serve as a source of novel mono-aromatic compounds following an additional lignin depolymerisation reaction.
- Miles-Barrett, Daniel M.,Neal, Andrew R.,Hand, Calum,Montgomery, James R.D.,Panovic, Isabella,Ojo, O. Stephen,Lancefield, Christopher S.,Cordes, David B.,Slawin, Alexandra M.Z.,Lebl, Tomas,Westwood, Nicholas J.
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supporting information
p. 10023 - 10030
(2016/11/06)
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- Antineoplastic Agents. 585. Isolation of Bridelia ferruginea Anticancer Podophyllotoxins and Synthesis of 4-Aza-podophyllotoxin Structural Modifications
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Cytotoxic constituents of the terrestrial plant Bridelia ferruginea were isolated using bioactivity-guided fractionation, which revealed the presence of the previously known deoxypodophyllotoxin (1), isopicrodeoxypodophyllotoxin (2), β-peltatin (3), β-pel
- Pettit, George R.,Searcy, Justin D.,Tan, Rui,Cragg, Gordon M.,Melody, Noeleen,Knight, John C.,Chapuis, Jean-Charles
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p. 507 - 518
(2016/04/19)
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- Anti selective glycolate aldol reactions of (: S)-4-isopropyl-1-[(R)-1-phenylethyl]imidazolidin-2-one: application towards the asymmetric synthesis of 8-4′-oxyneolignans
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The anti selective glycolate aldol reactions of (S)-4-isopropyl-1-[(R)-1-phenylethyl]imidazolidin-2-one auxiliary have been standardized with high yields and excellent diastereoselectivities on various substituted aryl, allyl and alkyl aldehydes. The optimized reaction conditions were employed for the stereoselective synthesis of oxyneolignans.
- Gangar, Mukesh,Ittuveetil, Avinash,Goyal, Sandeep,Pal, Anang,Harikrishnan,Nair, Vipin A.
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p. 102116 - 102126
(2016/11/09)
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- Unambiguous Identification of β-Tubulin as the Direct Cellular Target Responsible for the Cytotoxicity of Chalcone by Photoaffinity Labeling
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Chalcone is a simple and potentially privileged structure in medicinal chemistry with a diverse repertoire of biological activities, among which cytotoxicity is of particular interest. The sharp structure–activity relationship (SAR) for chalcone's cytotoxicity suggests structure-specific target interactions. Despite the numerous putative targets proposed, evidence for direct target interactions in cells is unavailable. In this study, guided by the sharp cytotoxic SAR, we developed a cytotoxic chalcone-based photoaffinity labeling (PAL) probe, (E)-3-(3-azidophenyl)-1-[3,5-dimethoxy-4-(prop-2-yn-1-yloxy)phenyl]-2-methylprop-2-en-1-one (C95; IC50: 0.38±0.01 μm), along with two structurally similar non-cytotoxic probes. These probes were used to search for the direct cellular target responsible for chalcone's cytotoxicity through intact cell-based PAL experiments, in which β-tubulin was identified to specifically interact with the cytotoxic probe (i.e., C95) but not the non-cytotoxic probes. A set of phenotypical and biochemical assays further reinforced β-tubulin as the cytotoxic target of chalcones. Peptide mass quantitation by mass spectrometric analysis revealed one peptide potentially labeled by C95, providing information on chalcone's binding site on β-tubulin.
- Zhou, Bo,Yu, Xingxin,Zhuang, Chunlin,Villalta, Peter,Lin, Yong,Lu, Junxuan,Xing, Chengguo
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supporting information
p. 1436 - 1445
(2016/07/16)
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- Inverse electron demand hetero-Diels-Alder reaction in preparing 1,4-benzodioxin from o-quinone and enamine
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A process for synthesizing 1,4-benzodioxin, through oxidation of a phenol to an o-quinone followed by treatment with an enamine, has been developed. Adduct stereochemistry is found to be retained via this one-pot reaction. The method uses hypervalent iodine reagent under mild conditions and is compatible with a wide scope of phenols and enamines.
- Zhang, Jinsong,Taylor, Chris,Bowman, Erich,Savage-Low, Leo,Lodewyk, Michael W.,Hanne, Larry,Wu, Guang
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p. 6298 - 6302
(2013/11/06)
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- Molecular docking studies of (1E,3E,5E )-1,6-bis(substituted phenyl)-hexa-1,3,5-triene and 1,4-bis(substituted trans-styryl)benzene analogs as novel tyrosinase inhibitors
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We simulated the docking of the tertiary structure of mushroom tyrosinase with our compounds. From the structure-tyrosinase inhibitory activity relationship, it is notable that compounds 4, 8 and 11 showed similar or better activity rates than kojic acid which was used as a positive control. Compounds 17, 21, and 23 among benzene analogs that possess the same substituent showed significantly lower tyrosinase inhibitory effects. Therefore, we have confirmed that among the compounds showing better tyrosinase inhibitory effects than kojic acid, the compounds with triene analogs have better tyrosinase inhibitory effect than the compounds with benzene analogs. Docking simulation suggested the mechanism of compounds by several key residues which had possible hydrogen bonding interactions. The pharmacophore model underlined the features of active compounds, 4,4′-((1E,3E,5E )-hexa-1,3,5-triene-1,6-diyl)diphenol, 5,5′-((1E,3E,5E )-hexa-1,3,5-triene-1,6-diyl)bis(2-methoxy-phenol), and 5,5′-((1 E,3E,5E )-hexa-1,3,5-triene-1,6-diyl)dibenzene-1,3-diol among triene derivatives which had several hydrogen bond groups on both terminal rings. The soundness of the docking results and the agreement with the pharmacophores suggest that it can be conveniently exploited to design inhibitors with an improved affinity for tyrosinase.
- Ha, Young Mi,Lee, Hye Jin,Park, Daeui,Jeong, Hyoung Oh,Park, Ji Young,Park, Yun Jung,Lee, Kyung Jin,Lee, Ji Yeon,Moon, Hyung Ryong,Chung, Hae Young
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- Anticancer effects of the metabolic products of the resveratrol analogue, DMU-212: Structural requirements for potency
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The methoxylated trans-stilbene resveratrol analogue, (E)-3,4,5,4′- tetramethoxystilbene (1), has shown promising antiproliferative activity in in vitro cell line and in vivo models. In vivo 1 gives rise to several metabolic products through demethylation or hydroxylation reactions at the stilbene moiety. In the present study we examined the anticancer activity of 1 and the metabolites (E)-3′-hydroxy-3,4,5,4′-tetramethoxystilbene (2), (E)-4′-hydroxy-3,4,5-trimethoxystilbene (3), (E)-4-hydroxy-3,5,4′- trimethoxystilbene (4) and (E)-3-hydroxy-4,5,4′-trimethoxystilbene (5) by means of cell viability testing, cell cycle analysis, immunostaining and Western blotting. Compounds 1 and 2 exhibited submicromolar toxicity in MCF-7 breast adenocarcinoma and HepG2 hepatoma cells, whereas 3, 4 and 5 were inactive in terms of inhibition of cellular proliferation. Incubation with 1 or 2 at 10 μM for 24 h induced apoptosis and G2/M cell cycle arrest in MCF-7 and HepG2 cells. Immunostaining of MCF-7 cells for β-tubulin in the presence of either 1 or 2 revealed shorter localization of the protein around the nucleus, as compared to control cells. Western blot analyses further demonstrated that treatment with either 1 or 2 at concentrations between 30 and 50 μM for 24 h caused a downregulation in the levels of β-tubulin and cyclin D1 expression and an upregulation in the levels of p53 expression in MCF-7 and HepG2 cells. 2 further increased the ratio of mRNA levels of the apoptosis-related genes Bax/Bcl-xL in both MCF-7 and HepG2 cells in a dose-dependent manner. We conclude that 2 inhibits HepG2 and MCF-7 cellular proliferation by inducing apoptosis and G2/M arrest through p53 and Bax/Bcl-xL upregulation. Our findings further demonstrate that trimethoxy substitutions along with the presence of a methoxy group at position 4′ are necessary for retaining the activity of 1.
- Androutsopoulos, Vasilis P.,Ruparelia, Ketan C.,Papakyriakou, Athanasios,Filippakis, Harilaos,Tsatsakis, Aristeidis M.,Spandidos, Demetrios A.
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experimental part
p. 2586 - 2595
(2011/06/21)
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- Antineoplastic agents. 579. Synthesis and cancer cell growth evaluation of E-stilstatin 3: A resveratrol structural modification
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As an extension of our earlier structure/activity investigation of resveratrol (1a) cancer cell growth inhibitory activity compared to the structurally related stilbene combretastatin series (e.g., 2a), an efficient synthesis of E-stilstatin 3 (3a) and its phosphate prodrug 3b was completed. The trans-stilbene 3a was obtained using a convergent synthesis employing a Wittig reaction with phosphonium bromide 9 as the key reaction step. Deprotection of the Z-silyl ether 13 gave E-stilstatin 3 (3a) as the exclusive product. The structure and stereochemistry of 3a was confirmed by X-ray crystal structure determination.
- Pettit, George R.,Melody, Noeleen,Thornhill, Andrew,Knight, John C.,Groy, Thomas L.,Herald, Cherry L.
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experimental part
p. 1637 - 1642
(2010/03/31)
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- Development of synthetic methodology suitable for the radiosynthesis of combretastatin A-1 (CA1) and its corresponding prodrug CA1P
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Synthetic methodology has been established suitable for the preparation of combretastatin A-1 (CA1) and its corresponding phosphate prodrug salt (CA1P) in high specific activity radiolabeled form. Judicious selection of appropriate phenolic protecting groups to distinguish positions on the A-ring from the B-ring of the stilbenoid was paramount for the success of this project. Methylation of the C-4' phenolic moiety by removal of the tert- butyldimethylsilyl protecting group in the presence of methyl iodide was accomplished in excellent yield without significant Z to E isomerization. This step (carried out with 12C-methyl iodide as proof of concept in this study) represents the process in which a 14C radioisotope could be incorporated in an actual radiosynthesis. CA1 is a natural product isolated from the African bush willow tree (Combretum caffrum) that has important medicinal value due, in part, to its ability to inhibit tubulin assembly. As a prodrug, CA1P (OXi4503) is in human clinical trials as a vascular disrupting agent.
- Shirali, Anupama,Sriram, Madhavi,Hall, John J.,Nguyen, Benson L.,Guddneppanavar, Rajsekhar,Hadimani, Mallinath B.,Ackley, J. Freeland,Siles, Rogelio,Jelinek, Christopher J.,Arthasery, Phyllis,Brown, Rodney C.,Murrell, Victor Leon,McMordie, Austin,Sharma, Suman,Chaplin, David J.,Pinney, Kevin G.
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experimental part
p. 414 - 421
(2009/12/05)
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- The brosimum allene: A structural revision
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(Chemical Equation Presented) Insight derived from a synthetic model, calculated 13C NMR data, and comparison to experimental data indicate that the proposed allenic structure A, originally assigned to an isolate from Brosimum acutifolium Huber
- Hu, Gaojie,Liu, Kai,Williams, Lawrence J.
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supporting information; experimental part
p. 5493 - 5496
(2009/06/06)
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- Total synthesis of (±)-nitidanin and novel procedures for determination of the location of the side chains on 1,4-benzodioxane
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Regioselective cycloaddition of o-quinone 4 and protected sinapyl alcohol 2 gave 1,4-benzodioxane 5, which was converted to (±)-nitidanin (6), an antimalarial compound. Two novel procedures were developed to determine the location of the side chains of th
- Kuboki, Atsuhito,Yamamoto, Toru,Taira, Mamie,Arishige, Tetsuya,Ohira, Susumu
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p. 771 - 774
(2007/10/03)
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- HIV REPLICATION INHIBITING PURINE DERIVATIVES
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The present invention relates to the use of a compound of formula (I) for the manufacture of a medicament for the prevention or the treatment of HIV infection wherein the compound of formula (I) is a compound of formula (I) a N-oxide, a pharmaceutically a
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(2010/02/11)
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- Stilbene derivatives as anticancer agents
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The present invention relates to stilbene derivatives which possess utility as anti-cancer agents. The compounds can be used to treat cancers which are susceptible to treatment therewith, and can be utilized in a method of treating such cancers. Pharmaceu
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- Formation of Carbon-Carbon Bonds via Quinone Methide-Initiated Cyclization Reactions
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p-Quinone methides were found to be excellent electrophilic cyclization initiators for the formation of six-membered rings.Cyclizations to form five- and seven-membered rings were also studied.Oxidation of 2,6-disubstituted phenols with Ag2O afforded the
- Angle, Steven R.,Arnaiz, Damian O.,Boyce, James P.,Frutos, Rogelio P.,Louie, Michael S.,et al.
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p. 6322 - 6337
(2007/10/02)
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- Synthesis and Evaluation of Analogues of (Z)-1-(4-Methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene as Potential Cytotoxic and Antimitotic Agents
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A series of stilbenes has been prepared and tested for cytotoxicity in the five human cancer cell lines A-549 non-small cell lung, MCF-7 breast, HT-29 colon, SKMEL-5 melanoma, and MLM melanoma.The cis stilbenes 6a-f proved to be cytotoxic in all five cell
- Cushman, Mark,Nagatarathnam, Dhanapalan,Gopal, D.,He, Hu-Ming,Lin, Chii M.,Hamel, Ernest
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p. 2293 - 2306
(2007/10/02)
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- Tricyclic heterocyclic derivatives
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The invention relates to tricyclic heterocyclic derivatives, or pharmaceutically-acceptable salts or in vivohydrolysable esters thereof, which possess anti-cancer activity. The invention also relates to processes for the manufacture of said tricyclic hete
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- PHENOL DERIVATIVES, PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS AND PROCESSES FOR THE PREPARATION OF THESE COMPOUNDS AND COMPOSITIONS
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Phenol derivatives of the formula (I) wherein A and B have the same or different meanings and each represent one of the groups ?C=C?, cis?CH=CH? or trans?CH=CH?, R1 is hydrogen, an optionally substituted alkyl or phenyl group or a cycloalkyl group, R2 is hydrogen, methyl or ethyl, R3 represents hydrogen, acetyl or propionyl, R4 has the same meaning as R3 or represents an alkyl group, R5 is a carboxylic or a hydroxy group or a functional derivative of such groups or R5 is a nitrile group and R6 is hydrogen, an alkyl group or the group OR4 which specifically inhibit 5-lipoxygenase and are useful in pharmaceutical compositions for prophylaxis and treatment of diseases due to the action of leukotrienes. The compounds are prepared by reacting suitable acetylene compounds or metal derivatives thereof with alkyl or aryl halides or by means of Wittig reactions optionally followed by transforming the member R5 into another carboxylic acid derivative. By hydrogenation A and B may be varied within the scope of the definition.
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- Phenol derivatives and pharmaceutical compositions containing these compounds
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Phenol derivatives of the formula STR1 wherein A and B have the same or different meanings and each represent one of the groups --C C--, cis--CH=CH-- or trans--CH=CH--, R1 is hydrogen, an optionally substituted alkyl or phenyl group or a cycloalkyl group, R2 is hydrogen, methyl or ethyl, R3 represents hydrogen, acetyl or propionyl, R4 has the same meaning as R3 or represents an alkyl group, R5 is a carboxylic or a hydroxy group or a functional derivative of such groups or R5 is a nitrile group and R6 is hydrogen, an alkyl group or the group OR4 which specifically inhibit 5-lipoxygenase and are useful in pharmaceutical compositions for prophylaxis and treatment of diseases due to the action of leukotrienes. The compounds are prepared by reacting suitable acetylene compounds or metal derivatives thereof with alkyl or aryl halides or by means of Wittig reactions optionally followed by transforming the member R5 into another carboxylic acid derivative. By hydrogenation A and B may be varied within the scope of the definition.
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