共查询到20条相似文献,搜索用时 15 毫秒
1.
《Bioorganic & medicinal chemistry》2016,24(20):4787-4790
Density functional theory (M06-2X) studies of the regioselectivity of 1,3-dipolar cycloaddition reactions of benzo and mesitonitrile oxides with alkynyl pinacol and MIDA boronates are reported. Calculated relative free energies of activation reproduce the experimentally observed product ratios. The electronic energies of activation are found to be mainly controlled by distortion energies required to achieve the transition states. Both electronic and steric effects influence regioselectivities. 相似文献
2.
Hornyák M Kele Z Kovács L Forgó P Howarth NM 《Nucleosides, nucleotides & nucleic acids》2006,25(8):867-870
The effect of the media (achiral and chiral ionic liquids) on the stereochemistry of intramolecular 1,3-dipolar cycloaddition reactions of D-galactose-derived omega-unsaturated nitrones, leading to bicyclic isoxazolidines, has been investigated. 相似文献
3.
Acetylene derivatives of phenylalanine, phenethylamine and the multifunctional unnatural amino acids, phenyl-bis-alanine and phenyl-tris-alanine, were synthesized and functionalized with 2-azidoethyl beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranoside via regioselective copper(I)-mediated 1,3-dipolar cycloaddition to give a panel of mono-, di- and trivalent lactoside derivatives. Evaluation of the compounds as inhibitors against the tumour- and inflammation-related galectin-1, -3, -4N, -4C, -4, -7, -8N and -9N revealed a divalent compound with a Kd value as low as 3.2 microM for galectin-1, which corresponded to a relative potency of 30 per lactose unit as compared to the natural disaccharide ligand lactose. This divalent compound had at least one order of magnitude higher affinity for galectin-1 than for any of the other galectins investigated. 相似文献
4.
Lindsay E. Chatkewitz John F. Halonski Marshall S. Padilla Douglas D. Young 《Bioorganic & medicinal chemistry letters》2018,28(2):81-84
The prevalence of 1,3-dipolar cycloadditions of azides and alkynes within both biology and chemistry highlights the utility of these reactions. However, the use of a copper catalyst can be prohibitive to some applications. Consequently, we have optimized a copper-free microwave-assisted reaction to alleviate the necessity for the copper catalyst. A small array of triazoles was prepared to examine the scope of this approach, and the methodology was translated to a protein context through the use of unnatural amino acids to demonstrate one of the first microwave-mediated bioconjugations involving a full length protein. 相似文献
5.
Stecko S Jurczak M Urbańczyk-Lipkowska Z Solecka J Chmielewski M 《Carbohydrate research》2008,343(13):2215-2220
The 1,3-dipolar cycloaddition of cyclic nitrone derived from tartaric acid and (S)-5-hydroxymethyl-2(5H)-furanone leads to a single adduct which was transformed into 2,6-dihydroxyhastanecine via reaction sequence involving reduction of the lactone moiety, glycolic cleavage of the terminal diol, and the N-O hydrogenolysis followed by the intramolecular alkylation of the nitrogen atom. 相似文献
6.
Ranjith Kumar R Perumal S Menéndez JC Yogeeswari P Sriram D 《Bioorganic & medicinal chemistry》2011,19(11):3444-3450
The 1,3-dipolar cycloaddition of nitrile oxides generated in situ from benzohydroximinoyl chloride and triethylamine to 2-aminopyranopyridine-3-carbonitriles and 2-aminochromene-3-carbonitriles occurred chemoselectively furnishing novel 1,2,4-oxadiazole-pyranopyridine/chromene hybrid heterocycles in moderate yields. In vitro screening of these compounds against Mycobacterium tuberculosis H37Rv (MTB) disclosed that the 1,2,4-oxadiazole-pyranopyridine hybrids display enhanced activity relative to the 1,2,4-oxadiazole-chromene hybrids. Among the compounds screened, 3-[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]-4-(2,4-dichlorophenyl)-8-[(E)-(2,4-dichlorophenyl)-methylidene]-6-methyl-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridin-2-amine (MIC: 0.31 μM) is 1.2, 15.2 and 24.6 times more active than standard antitubercular drugs, viz. isoniazid, ciprofloxacin and ethambutol, respectively. 相似文献
7.
Hatem Layeb Abdelmalek Khorief Nacereddine Abdelhafid Djerourou Mar Ríos-Gutiérrez Luis R. Domingo 《Journal of molecular modeling》2015,21(5):104
The mechanism of the [3+2] cycloaddition (32CA) reaction of C-phenyl-N-methylnitrone with ethyl trifluoroacetoacetate has been theoretically studied at the MPWB1K/6-311G(d,p) level. This 32CA reaction, in which the enol form of the β-keto ester participates as the ethylene component, takes place with complete ortho regioselectivity and exo stereoselectivity. The presence of the CF3 group in the β-position in the enol acetate accelerates the 32CA reaction, but it does not modify the regioselectivity, which is controlled by the presence of the ester group. While ortho regioselectivity is reproduced by the MPWB1K calculations, the endo selectivity is not. The inclusion of solvent effects slightly decreases the reactivity but does not modify the gas phase selectivities. Analysis of the DFT global reactivity indices and the Parr functions in reagents provide a rationalization for the participation of ethyl trifluoroacetoacetate and the regioselectivity in this zw-type 32CA reaction. 相似文献
8.
The synthesis of 2-phenyl-3-aryl and 2-phenyl-3-aroyl derivatives 5-(1,2-O-isopropylidene-alpha-D-xylo-tetrofuranos-4-yl)isoxazolidi ne (3) from nitrones and 5,6-dideoxy-1,2-O-isopropylidene-alpha-D-xylo-hex-5- enofuranose (1) is described. The 1,3-dipolar cycloaddition reactions given mainly anti adducts 3 and 4 (greater than or equal to 95% pi-facial stereoselectivity). The cycloadducts 3 with H-3,5 cis are formed either exclusively or preponderate over the trans diastereoisomers 4. 相似文献
9.
Pádár P Forgó P Kele Z Howarth NM Kovács L 《Nucleosides, nucleotides & nucleic acids》2005,24(5-7):743-745
The diastereoselective intramolecular 1,3-dipolar cycloaddition reaction of unsaturated nitrones, derived from methyl alpha-D-glucopyranoside with 2-furaldehyde and 2-(benzyloxy)acetaldehyde has been studied In our pevious studies with 2-furaldehyde, the cycloaddition resulted 3 diastereoisomers in a 3:1:1 ratio. In this article, how the number of the possible isomers generated by 1,3-cycloaddition could be reduced from 4 to 1 when 2-(benzyloxy)acetaldehyde was employed as an aldehyde is shown. 相似文献
10.
Abdulrahman I. Almansour Sadath Ali Mohamed Ashraf Ali Rusli Ismail Tan Soo Choon Velmurugan Sellappan Karthi keyan Elumalai Suresh Pandian 《Bioorganic & medicinal chemistry letters》2012,22(24):7418-7421
A series of dispiropyrrolothiazoles compounds were synthesized using 1,3-dipolar cycloaddition and were screened for antimycobacterial activity against Mycobacterium tuberculosis H37Rv and INH resistant M. tuberculosis strains. Two of them were showing good activity with MIC of less than 1 μM. Compound (5f) was found to be the most active with MIC of 0.210 and 8.312 μM respectively. 相似文献
11.
Quercetin 2,3-dioxygenase (QDO) is an enzyme which accepts various transition metal ions as cofactors, and cleaves the heterocyclic ring of quercetin with consumption of dioxygen and release of carbon monoxide. QDO from B. subtilis that binds Mn(II) displays an unprecedented nitroxygenase activity, whereby nitroxyl (HNO) is incorporated into quercetin cleavage products instead of dioxygen. Interestingly, the reaction proceeds with high regiospecificity, i.e., nitrogen and oxygen atoms of HNO are incorporated into specific fragments of the cleavage product. A nonenzymatic base-catalyzed reaction, which occurs in pH above 7.5, yields the same reaction products. Herein, we report results of quantum chemical studies on the mechanisms of the nitroxygenase reaction of Mn-QDO. Density functional method with dispersion correction (B3LYP-D3) was applied to the Mn-QDO active site model and the reactants of the nonenzymatic reaction. Co(II)- and Fe(II)-variants of the active site were also considered. Analysis of reaction energy profiles suggests that the regiospecificity of the reaction is an inherent property of the reactants, whereas the unique reactivity of Mn-QDO, as opposed to Co- or Fe-QDO that do not catalyze nitroxygenation, stems from weak HNO binding and lack of strong preference for coordination of HNO through the nitrogen atom. Moreover, the enzyme activates quercetin through deprotonation and the proton acceptor—Glu69 needs to reorient for the reaction to proceed. 相似文献
12.
van Teeffelen S Shaevitz JW Gitai Z 《BioEssays : news and reviews in molecular, cellular and developmental biology》2012,34(5):427-436
Fluorescence microscopy is the primary tool for studying complex processes inside individual living cells. Technical advances in both molecular biology and microscopy have made it possible to image cells from many genetic and environmental backgrounds. These images contain a vast amount of information, which is often hidden behind various sources of noise, convoluted with other information and stochastic in nature. Accessing the desired biological information therefore requires new tools of computational image analysis and modeling. Here, we review some of the recent advances in computational analysis of images obtained from fluorescence microscopy, focusing on bacterial systems. We emphasize techniques that are readily available to molecular and cell biologists but also point out examples where problem-specific image analyses are necessary. Thus, image analysis is not only a toolkit to be applied to new images but also an integral part of the design and implementation of a microscopy experiment. 相似文献
13.
14.
Welch JJ 《Proceedings. Biological sciences / The Royal Society》2009,276(1657):675-682
The island rule states that after island colonization, larger animals tend to evolve reduced body sizes and smaller animals increased sizes. Recently, there has been disagreement about how often, if ever, this rule applies in nature, and much of this disagreement stems from differences in the statistical tests employed. This study shows, how different tests of the island rule assume different null hypotheses, and that these rely on quite different biological assumptions. Analysis and simulation are then used to quantify the biases in the tests. Many widely used tests are shown to yield false support for the island rule when island and mainland evolution are indistinguishable, and so a Monte Carlo permutation test is introduced that avoids this problem. It is further shown that tests based on independent contrasts lack power to detect the island rule under certain conditions. Finally, a complete reanalysis is presented of recent data from primates. When head-body length is used as the measure of body size, reports of the island rule are shown to stem from methodological artefacts. But when skull length or body mass are used, all tests agree that the island rule does hold in primates. 相似文献
15.
Principal component analysis as an alternative treatment for morphometric characters: phylogeny of caseids as a case study
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In a recent study, the phylogeny of Caseidae (a herbivorous family of Palaeozoic synapsids belonging to the paraphyletic grade known as pelycosaurs) was analysed with a dataset employing more than three hundred continuous morphological characters in an effort to follow the principles of total evidence. Continuous characters are a source of great debate, with disagreements surrounding their suitability for and treatment in phylogenetic analysis. A number of shortcomings were identified in the handling of continuous characters in this study of caseids, including the use of gap weighting to discretize the characters and potential issues with redundancy and character non‐independence. Therefore, an alternative treatment for these characters is suggested here. First, rather than using gap weighting, the continuous characters were analysed in the program TNT, in which the raw values can be treated as continuous rather than discrete. Second, prior to the phylogenetic analysis, the continuous characters were subjected to a log‐ratio principal component analysis, and then the principal components were included in the character matrix rather than the raw ratios. Analysing the original data in TNT produced little difference in the results, but using the principal components as continuous characters resulted in alternative positions for Caseopsis agilis, Ennatosaurus tecton and Caseoides sanangeloensis. The differences are judged to be due to the reduced redundancy of the characters, the smaller number of principal components not overwhelming the discrete characters and the use of a scaling method which allows principal components with a higher variance to have a greater influence on the analysis. The positions of highly fragmentary fossils depended heavily on the method used to treat the missing characters in the principal component analysis, and so the method proposed here is not recommended for analysing very incomplete taxa. 相似文献
16.
17.
Mario Vincenzo?La?Rocca Malvina?Rutkowski Stéphanie?Ringeissen Jér?me?Gomar Marie-Céline?Frantz Saliou?Ngom Carlo?Adamo
The overall objective was to identify an accurate computational electronic method to virtually screen phenolic compounds through their antioxidant and free-radical scavenging activity. The impact of a key parameter of the density functional theory (DFT) approach was studied. Performances of the 21 most commonly used exchange-correlation functionals are thus detailed in the evaluation of the main energetic parameters related to the activities of two prototype antioxidants, namely quercetin and edaravone, is reported. These functionals have been chosen among those belonging to three different families of hybrid functionals, namely global, range separated, and double hybrids. Other computational parameters have also been considered, such as basis set and solvent effects. The selected parameters, namely bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) allow a mechanistic evaluation of the antioxidant activities of free radical scavengers. Our results show that all the selected functionals provide a coherent picture of these properties, predicting the same order of BDEs and PDEs. However, with respect to the reference values, the errors found at CBS-Q3 level significantly vary with the functional. Although it is difficult to evidence a global trend from the reported data, it clearly appears that LC-ωPBE, M05-2X, and M06-2X are the most suitable approaches for the considered properties, giving the lowest cumulative mean absolute errors. These methods are therefore suggested for an accurate and fast evaluation of energetic parameters related to an antioxidant activity via free radical scavenging. 相似文献
18.
Edson Romano Nucci Antonio J. G. Cruz Roberto C. Giordano 《Bioprocess and biosystems engineering》2010,33(5):557-564
The complexity of biological processes often makes impractical the development of detailed, structured phenomenological models
of the cultivation of microorganisms in bioreactors. In this context, data pre-treatment techniques are useful for bioprocess
control and fault detection. Among them, principal component analysis (PCA) plays an important role. This work presents a
case study of the application of this technique during real experiments, where the enzyme penicillin G acylase (PGA) was produced
by Bacillus megaterium ATCC 14945. PGA hydrolyzes penicillin G to yield 6-aminopenicilanic acid (6-APA) and phenyl acetic acid. 6-APA is used to
produce semi-synthetic β-lactam antibiotics. A static PCA algorithm was implemented for on-line detection of deviations from
the desired process behavior. The experiments were carried out in a 2-L bioreactor. Hotteling’s T
2 was the discrimination criterion employed in this multivariable problem and the method showed a high sensibility for fault
detection in all real cases that were studied. 相似文献
19.
Harzsch, S. and Wanninger, A. 2010. Evolution of invertebrate nervous systems: the Chaetognatha as a case study. —Acta Zoologica (Stockholm) 91 : 35–43 Although recent molecular studies indicate that Chaetognatha may be one of the earliest Bilaterian offshoots, the phylogenetic position of this taxon still is a matter of ongoing debate. In this contribution, we review recent attempts to contribute phylogenetic information on the Chaetognatha by analysing structure and development of their nervous system (neurophylogeny). Analysing this group of organisms also has a major impact on our understanding of nervous system evolution in Bilateria. We review recent evidence from this field and suggest that Urbilateria already was equipped with the genetic toolkit required to build a complex, concentrated central nervous system (CNS), although this was not expressed phenotypically so that Urbilateria was equipped with a nerve plexus and not a CNS. This implies that in the deep metazoan nodes, concentration of the ancestral plexus occurred twice independently, namely once after the protostome–deuterostome split on the branch leading to the protostomes (resulting in a ventrally positioned nerve cord) and once along the chordate line (with a dorsal nerve cord). 相似文献
20.
Maheswari SU Balamurugan K Perumal S Yogeeswari P Sriram D 《Bioorganic & medicinal chemistry letters》2010,20(24):7278-7282
A facile 1,3-dipolar cycloaddition of azomethine ylide generated in situ from the reaction of 1,3-thiazolane-4-carboxylic acid and isatin to 2-arylidene-1,3-indanediones furnished novel dispiro-oxindolylpyrrolothiazoles regio- and stereo-selectively in moderate to good yields (60-92%). In vitro antitubercular screening of 27 compounds against Mycobacterium tuberculosis H37Rv (MTB) disclosed that spiro[5.3']-5'-nitrooxindolespiro-[6.3″]-1H-inden-1″,3″(2H)-dione-7-(4-bromophenyl)tetrahydro-1H-pyrrolo[1,2-c][1,3]thiazole has the maximum potency with a minimum inhibitory concentration (MIC) of 1.4 μM against MTB, being 3.4 and 5.4 times more potent than ciprofloxacin and ethambutol, respectively. 相似文献