- Micellar Catalysis for Sustainable Hydroformylation
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It is here reported a fully sustainable and generally applicable protocol for the regioselective hydroformylation of terminal alkenes, using cheap commercially available catalysts and ligands, in mild reaction conditions (70 °C, 9 bar, 40 min). The process can take advantages from both micellar catalysis and microwave irradiation to obtain the linear aldehydes as the major or sole regioisomers in good to high yields. The substrate scope is largely explored as well as the application of hydroformylation in tandem with intramolecular hemiacetalization thus demonstrating the compatibility with a broad variety of functional groups. The reaction is efficient even in large scale and the catalyst and micellar water phase can be reused at least 5 times without any impact in reaction yields. The efficiency and sustainability of this protocol is strictly related to the in situ transformation of the aldehyde into the corresponding Bertagnini's salt that precipitates in the reaction mixture avoiding organic solvent mediated purification steps to obtain the final aldehydes as pure compounds.
- Calamante, Massimo,Dei, Filippo,Maramai, Samuele,Migliorini, Francesca,Petricci, Elena
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p. 2794 - 2806
(2021/05/03)
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- Synthesis and evaluation of new sesamol-based phenolic acid derivatives with hypolipidemic, antioxidant, and hepatoprotective effects
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The objective of this study is to synthesize a series of sesamol-based phenolic acid derivatives, which were designed by combination principle. The hypolipidemic activity of all these compounds was preliminarily screened by acute hyperlipidemic mice model induced by Triton WR 1339, in which compound T6 exhibited more significant reducing plasma TG and TC than fenofibrate. Compound T6 was also found to obviously decrease TG and TC both in the plasma and hepatic tissue of high-fat-diet-induced hyperlipidemic mice. Moreover, T6 showed hepatoprotective effects, which remarkable amelioration in characteristic liver enzymes was examined and the histopathological observation displayed that compound T6 inhibited lipids accumulation in the hepatic. The levels of PPAR-α receptor related to lipids metabolism in hepatic tissue were upregulated after T6 treatment. Other potent effects of T6 such as antioxidant and anti-inflammatory activity were also observed. On the bases of these findings, compound T6 may serve as an effective hypolipidemic and hepatoprotective agent. [Figure not available: see fulltext.]
- Xie, Yundong,Liu, Jiping,Shi, Yongheng,Bin Wang,Wang, Xiaoping,Wang, Wei,Sun, Meng,Xu, Xinya,He, Shipeng
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p. 1688 - 1702
(2021/07/26)
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- Beyond Basicity: Discovery of Nonbasic DENV-2 Protease Inhibitors with Potent Activity in Cell Culture
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The viral serine protease NS2B-NS3 is one of the promising targets for drug discovery against dengue virus and other flaviviruses. The molecular recognition preferences of the protease favor basic, positively charged moieties as substrates and inhibitors, which leads to pharmacokinetic liabilities and off-target interactions with host proteases such as thrombin. We here present the results of efforts that were aimed specifically at the discovery and development of noncharged, small-molecular inhibitors of the flaviviral proteases. A key factor in the discovery of these compounds was a cellular reporter gene assay for the dengue protease, the DENV2proHeLa system. Extensive structure-activity relationship explorations resulted in novel benzamide derivatives with submicromolar activities in viral replication assays (EC50 0.24 μM), selectivity against off-target proteases, and negligible cytotoxicity. This structural class has increased drug-likeness compared to most of the previously published active-site-directed flaviviral protease inhibitors and includes promising candidates for further preclinical development.
- Kühl, Nikos,Leuthold, Mila M.,Behnam, Mira A. M.,Klein, Christian D.
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p. 4567 - 4587
(2021/05/06)
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- A New Class of Dengue and West Nile Virus Protease Inhibitors with Submicromolar Activity in Reporter Gene DENV-2 Protease and Viral Replication Assays
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Dengue and West Nile virus are rapidly spreading global pathogens for which no specific therapeutic treatments are available. One of the promising targets for drug discovery against dengue and other flaviviruses is the viral serine protease NS2B-NS3. We present the design, synthesis, and in vitro and cellular characterization of a novel chemotype of potent small-molecule non-peptidic dengue protease inhibitors derived from 4-benzyloxyphenylglycine. A newly developed luciferase-based DENV-2 protease reporter system in HeLa cells (DENV2proHeLa) was employed to determine the activity of the compounds in a cellular environment. Specificity and selectivity of the DENV2proHeLa system were confirmed by viral titer reduction assays. The compounds reach low micromolar to upper nanomolar inhibitory potency in cell-based assays, are selective against other serine proteases, and do not show relevant cytotoxicity. An extensive structure-activity relationship study provides a perspective for further drug development against flaviviral infections.
- Kühl, Nikos,Graf, Dominik,Bock, Josephine,Behnam, Mira A. M.,Leuthold, Mila-Mareen,Klein, Christian D.
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supporting information
p. 8179 - 8197
(2020/09/21)
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- HIF-1α inhibitors: Synthesis and biological evaluation of novel moracin O and P analogues
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The natural products moracins O and P exhibited potent in vitro inhibitory activity against hypoxia-inducible factor (HIF-1), which is a key mediator during adaptation of cancer cells to tumour hypoxia. Systematic variations of the structures of benzofuran type moracins were made and structure-activity relationship analysis showed the importance of the 2-arylbenzofuran ring and the (R)-configuration of the core scaffold. Further evaluation of the representative compound 5 showed its inhibitory effect on HIF-1α protein accumulation and target gene expression under hypoxia.
- Xia, Yan,Jin, Yinglan,Kaur, Navneet,Choi, Yongseok,Lee, Kyeong
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supporting information; experimental part
p. 2386 - 2396
(2011/06/21)
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- COMPOSITIONS AND METHODS FOR GLUCOSE TRANSPORT INHIBITION
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Glucose deprivation is an attractive strategy in cancer research and treatment. Cancer cells upregulate glucose uptake and metabolism for maintaining accelerated growth and proliferation rates. Specifically blocking these processes is likely to provide new insights to the role of glucose transport and metabolism in tumorigenesis, as well as in apoptosis. As solid tumors outgrow the surrounding vasculature, they encounter microenvironments with a limited supply of nutrients leading to a glucose deprived environment in some regions of the tumor. Cancer cells living in the glucose deprived environment undergo changes to prevent glucose deprivation-induced apoptosis. Knowing how cancer cells evade apoptosis induction is also likely to yield valuable information and knowledge of how to overcome the resistance to apoptosis induction in cancer cells. Disclosed herein are novel anticancer compounds that inhibit basal glucose transport, resulting in tumor suppression and new methods for the study of glucose deprivation in animal cancer research.
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Page/Page column 27-28
(2011/10/13)
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- Synthesis, radical scavenging activity, protection during storage, and frying by novel antioxidants
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Novel antioxidants, derivatives of trolox, and selected phenolic acids have been prepared in good yields and fully characterized by 1H NMR, 13C NMR, and MS. Their antioxidant activities have been assessed by DPPH and ORAC assays, and during frying and accelerated storage tests. Novel phenolic compounds exhibited higher radical scavenging activities than both trolox and R-tocopherol. Trolox hydroxybenzoate showed a significantly higher protection than R-tocopherol under storage conditions. All new antioxidants performed better than R-tocopherol under frying conditions. Moreover, their outstanding thermal stability makes them more valuable than R-tocopherol for frying applications.
- Catel, Yohann,Aladedunye, Felix,Przybylski, Roman
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scheme or table
p. 11081 - 11089
(2011/06/21)
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- Novel inhibitors of basal glucose transport as potential anticancer agents
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Cancer cells commonly show increased levels of glucose uptake and dependence. A potential strategy for the treatment of cancer may be the inhibition of basal glucose transport. We report here the synthesis of a small library of polyphenolic esters that inhibit basal glucose transport in H1299 lung and other cancer cells. These basal glucose transport inhibitors also inhibit cancer cell growth in H1299 cells, and these two activities appear to be correlated.
- Zhang, Weihe,Liu, Yi,Chen, Xiaozhuo,Bergmeier, Stephen C.
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scheme or table
p. 2191 - 2194
(2010/06/15)
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- Counterattack mode differential acetylative deprotection of phenylmethyl ethers: Applications to solid phase organic reactions
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A counterattack protocol for differential acetylative cleavage of phenylmethyl ether has been developed. The phenylmethyl moiety is liberated as benzyl bromide that is isolated and reused providing advantages in terms of waste minimization/utilization and atom economy. The applicability of this methodology has been extended for solid phase organic reactions with the feasibility of reuse of the solid support.
- Chakraborti, Asit K.,Chankeshwara, Sunay V.
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supporting information; experimental part
p. 1367 - 1370
(2009/07/04)
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- Semi-synthesis and proteasome inhibition of D-ring deoxy analogs of (-)-epigallocatechin gallate (EGCG), the active ingredient of green tea extract
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A semi-synthetic route to the D-ring analogs of (-)-epigallocatechin gallate (EGCG) from the relatively abundant (-)-epigallocatechin (EGC), isolated from, green tea leaves, is described. A natural product (13), found in Cistus salvifolius, its acetate (14) and analog (17) were synthesized by this method. Their inhibitory activities against proteasomes were investigated.
- Huo, Congde,Shi, Guoqing,Lam, Wai Har,Chen, Di,Cui, Quizhi Cindy,Dou, Q. Ping,Chan, Tak Hang
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p. 495 - 502
(2008/09/21)
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- First chemical synthesis of three natural depsides involved in flavonol catabolism and related to quercetinase catalysis
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We report here the first chemical synthesis of three depsides related to quercetinase-catalyzed degradation of kaempferol, quercetin, and myricetin. The three depsides were constructed through the coupling of suitably protected phloroglucinol carboxylic acid and hydroxy-perbenzylated, derivatives of gallic, protocatechuic, and 4-hydroxy benzoic acids. The three synthesized target compounds proved to be identical to their natural counterparts, arising from quercetinase action on corresponding flavonols. Copyright Taylor & Francis Group, LLC.
- Tranchimand, Sylvain,Tron, Thierry,Gaudin, Christian,Iacazio, Gilles
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p. 587 - 597
(2007/10/03)
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- Synthesis of functionalised 2-aryl-5-nitro-1H-indoles and their activity as bacterial NorA efflux pump inhibitors
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In order to develop structure-activity relationships and to provide access to antibacterial agents for dual action studies, a variety of aryl group-substituted 2-aryl-5-nitro-1H-indoles were synthesized and the activity of the compounds assessed as inhibitors of the NorA multidrug resistance pump in the bacterium Staphylococcus aureus. The NorA protein from the major facilitator superfamily of efflux pumps confers resistance to a variety of structurally dissimilar antimicrobials such as norfloxacin, ethidium bromide, berberine and acriflavin. The compound [4-benzyloxy-2-(5-nitro-1H-2-yl)-phenyl]-methanol was the most potent pump inhibitor.
- Samosorn, Siritron,Bremner, John B.,Ball, Anthony,Lewis, Kim
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p. 857 - 865
(2007/10/03)
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- A simple and effective method for chemoselective esterification of phenolic acids
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A new method for efficient and chemoselective esterification of phenolic acids in KHCO3/alkyl halide/DMF reaction system is described, by which a series of phenoic acid esters were obtained in excellent yields.
- Guo, Wei,Li, Junfei,Fan, Ningjuan,Wu, Weiwei,Zhou, Peiwen,Xia, Chizhong
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p. 145 - 152
(2007/10/03)
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- Structure - Activity relationships of non-imidazole H3 receptor ligands. Part 1
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SAR studies for novel non-imidazole containing H3 receptor antagonists with high potency and selectivity for rat H3 receptors are described. A high throughput screening lead, A-923, was further elaborated in a systematic manner to clarify a pharmacophore for this class of aryloxyalkyl piperazine based compounds.
- Faghih, Ramin,Dwight, Wesley,Gentles, Robert,Phelan, Kathleen,Esbenshade, Timothy A,Ireland, Lynne,Miller, Thomas R,Kang, Chae-Hee,Fox, Gerard B,Gopalakrishnan, Sujatha M,Hancock, Arthur A,Bennani, Youssef L
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p. 2031 - 2034
(2007/10/03)
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- Biologically compatible linear block copolymers of polyalkylene oxide and peptide units
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A linear block copolymer comprising units of an alkylene oxide, linked to units of peptide via a linking group comprising a --CH2 CHOHCH2 N(R)-- moiety, is useful as an imaging agent, drug, prodrug or as a delivery system for imaging agents, drugs or prodrugs.
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- The synthesis and characterisation of a novel thiophene-based liquid crystal exhibiting ferro-, ferri- and antiferro-electric phase types
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The synthesis and liquid crystal properties of (R)-(-)-4-(l-methylheptyloxycarbonyl)phenyl 5-(4-decyloxyphenyl)thiophene-2carboxylate is reported. This material exhibits the following phase types (°C): I 97.4 SA 92.2 Sc*81.4 ferri 78.8 antiferroelectric 48.6 glass state (characterised by thermal optical microscopy and differential scanning calorimetry). Results from electro-optical investigations, for example, field-induced transitions, temperature and voltage dependence and current and electro-optic response, clearly illustrate the presence of the Sc* ferro-, ferri- and antiferro-electric phase types.
- Byron, David J.,Komitov, Lachezar,Matharu, Avtar S.,McSherry, Ian,Wilson, Robert C.
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p. 1871 - 1878
(2007/10/03)
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- Process for producing benzyl esters of aromatic hydroxycarboxylic acids
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Highly pure benzyl esters of aromatic hydroxycarboxylic acids are produced in high yields by reacting an aromatic hydroxycarboxylic acid or its lower alkyl ester with a benzyl alcohol in the presence of an organotin compound of the general formula STR1 wherein R's are identical or different and each represents an alkyl group having 1 to 8 carbon atoms or an aryl group, and Z represents an oxygen or sulfur atom, an organotin compound of the general formula wherein R is as defined, X represents a halogen atom or the group --OCOR1 in which R1 represents a saturated or unsaturated alkyl group having 1 to 18 carbon atoms or an aryl group, p is 2, 3 or 4, q is 0, 1 or 2, the sum of p and q is 4, and when q is 2, the two X's may be linked to each other to form the group --OCO--R2 --COO-- in which R2 represents a saturated or unsaturated alkylene group having 1 to 10 carbon atoms or an arylene group, or an organotitanium compound of the general formula wherein R is as defined.
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- Smectic-smectic phase transitions in binary liquid-crystalline mixtures of DB5-T8
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We have used high-resolution x-ray diffraction and ac calorimetry to study the liquid-crystalline smectic-A-smectic-A phase transitions in binary mixtures of polar mesogenic compounds DB5 phenyl ester> and T8 ethenyl> phenyl ester>.A detailed synthesis for each of these compounds is presented.The smectic A1 phase in this system shows two collinear diffuse x-ray maxima at incommensurate wave vectors, indicating a tendency to form the predicted Ai1 phase with two strongly coupled density modulations having incommensurate wavelengths.The Ad peak position, while both temperature and concentration dependent, is remarkably constant along the N-Ad phase boundary.In the vicinity of 16 mol percent T8, both the x-ray and heat-capacity results are reproducibly history dependent.The simultaneous observation of sharp A2 and Ad peaks most likely results from phase coexistence, but a condensed incommensurate Ai2 phase cannot be ruled out.
- Fontes, Ernest,Lee, Wah Keat,Heiney, Paul A.,Nounesis, George,Garland, Carl W.,et al.
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p. 3917 - 3929
(2007/10/02)
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- Biosynthesis of Phenanthroindolizidine Alkaloids: Incorporation of 2-Pyrrolidin-2-ylacetophenone and Benzoylacetic Acid and Derivatives
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2-Pyrrolidin-2-ylacetophenone (12) and its oxygenated derivatives, (13) and (14), bearing 14C and 3H labels are synthesized and are shown to be intact precursors for the phenanthroindolizidine alkaloid, tylophorinine (16), in Tylophora asthmatica; the three amines, singly labelled with tritium, are shown to be precursors for tylophorine (3) and tylophorinidine (17).Benzoylacetic acid (9) and p-hydroxybenzoylacetic acid (10), but not 4-hydroxy-3-methoxybenzoylacetic acid, are also precursors for tylophorinine (16).The results allow partial description of the biosynthetic pathways tophenanthroindolizidine alkaloids.A degradation is described which allowed the location of label in 2-pyrrolidin-2-ylacetophenone, derived from ornithine, to be established.
- Herbert, Richard B.,Jackson, Frederick B.,Nicolson, Ian T.
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p. 825 - 831
(2007/10/02)
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