Pillar[n]arenes are among the newest members of the macrocyclic family. Nevertheless, their conformational behavior and binding properties as well as redox properties of dealkylated pillar[n]arenes are well-studied. At the same time, introducing a heteroatom into a cyclophane macrocycle is already known to alter all the above properties drastically. This study presents a simple synthetic approach based on thia-Michael addition cyclization that readily resulted into hexathiapillar[6]arene with four phenylene units alternated by two redox-active hydroquinone moieties. The straightforward synthesis of the macrocycle enabled a systematic study of its conformation and redox behavior. The modification of hexathiapillar[6]arene afforded five functionalized derivatives, which were studied structurally in detail. The findings revealed interesting redox and structural properties of the macrocycle and its derivatives including the formation of crystal lattices with continuous channels and empty voids.
- Publikační typ
- časopisecké články MeSH
Aggregation of phthalocyanines (Pcs) represents a problematic feature that decreases the potential of these macrocycles in a number of applications. In this work, we present a supramolecular approach based on the interaction of aminoadamantyl-substituted Pcs with bulky and hydrophilic cucurbit[7]uril (CB[7]) to increase the levels of Pc monomers in water. A series of zinc(II) Pcs substituted at positions α or β by an aminoadamantyl substituent (with a different level of alkylation of nitrogen) were prepared from the corresponding phthalonitriles. A 1H nuclear magnetic resonance study of the interaction of phthalonitriles with CB[7] in water confirmed the formation of an inclusion complex with an aminoadamantyl moiety with Ka values of ∼1012 M-1. The interaction of CB[7] with Pcs in water substantially weakened H-type aggregation and improved both fluorescence and singlet oxygen production, confirming that this approach is efficient for the monomerization of Pcs. In vitro evaluation of the photodynamic activity of prepared Pcs led to EC50 values in the submicromolar range on HeLa and SK-MEL-28 cells. However, the activity decreased for at least an order of magnitude after host-guest interaction with CB[7] despite better photophysical properties. This was attributed to a much lower uptake by cells due to the very bulky and hydrophilic character of the Pc-CB[7] assembly.
- Publikační typ
- časopisecké články MeSH
A novel synthetic approach involving an Eschenmoser coupling reaction of substituted 3-bromooxindoles (H, 6-Cl, 6-COOMe, 5-NO2) with two substituted thiobenzanilides in dimethylformamide or acetonitrile was used for the synthesis of eight kinase inhibitors including Nintedanib and Hesperadin in yields exceeding 76%. Starting compounds for the synthesis are also easily available in good yields. 3-Bromooxindoles were prepared either from corresponding isatins using a three-step synthesis in an average overall yield of 65% or by direct bromination of oxindoles (yield of 65-86%). Starting N-(4-piperidin-1-ylmethyl-phenyl)-thiobenzamide was prepared by thionation of the corresponding benzanilide in an 86% yield and N-methyl-N-(4-thiobenzoylaminophenyl)-2-(4-methylpiperazin-1-yl)acetamide was prepared by thioacylation of the corresponding aniline with methyl dithiobenzoate in an 86% yield.
- MeSH
- indoly * MeSH
- oxindoly MeSH
- sulfonamidy * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
N-(3-Phenylprop-2-yn-1-yl)-sulfonamides derived from serine and threonine were synthesized using solid-phase synthesis and subjected to reaction with trimethylsilyl trifluoromethanesulfonate (TMSOTf). In contrast to the previously reported formation of 1,4-oxazepanes, this reaction afforded pyrrolidin-3-ones. A mechanistic explanation for this unexpected outcome is proposed, and the limitations and scope of the rearrangement are outlined.
Direct arylation and alkenylation of 1-substituted tetrazoles was achieved via Pd catalysis in the presence of CuI and Cs(2)CO(3). Unlike the related reactions of imidazoles and purines, phosphine ligand was necessary to prevent the intermediate tetrazolyl-Pd(II) species from fragmentation into the corresponding cyanamide. Various 1,5-disubstituted tetrazoles were prepared with good to excellent isolated yields.
Biologically interesting 2-substituted 4-alkylidene pentenolides were prepared with complete control of regio- and stereoselectivity from 2-iodo allylic alcohols via an array of Pd-catalyzed processes, including alkynylation with methyl propiolate, tributyltin hydride addition, and alpha-functionalization. Some of the compounds possess selective cytostatic activity against ovarian carcinoma HeLa S3 and leukemia CCRF-CEM cell lines.
- MeSH
- alkeny chemie MeSH
- antitumorózní látky farmakologie chemická syntéza chemie MeSH
- benzenové deriváty chemie MeSH
- financování organizované MeSH
- inhibiční koncentrace 50 MeSH
- katalýza MeSH
- lidé MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- palladium chemie MeSH
- propionáty farmakologie chemická syntéza chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
Photolysis of dihydroxy compounds (diols) protected as 2-nitrobenzylidene acetals (ONBA) and subsequent acid- or base-catalyzed hydrolysis of the 2-nitrosobenzoic acid ester intermediates result in an efficient and high-yielding release of the substrates. We investigated the scope and limitations of ONBA photochemistry and expanded upon earlier described two-step procedures to show that the protected diols of many structural varieties can also be liberated in a one-pot procedure. In view of the fact that the acetals of nonsymmetrically substituted diols are converted into one of the corresponding 2-nitrosobenzoic acid ester isomers with moderate to high regioselectivity, the mechanism of their formation was studied using various experimental techniques. The experimental data were found to be in agreement with DFT-based quantum chemical calculations that showed the preferential cleavage occurs on the acetal C-O bond in the vicinity of more electron-withdrawing (or less electron-donating) groups. The study also revealed considerable complexity in the cleavage mechanism and that the structural variations in the substrate can significantly alter the reaction pathway. This deprotection strategy was found to be also applicable for 2-thioethanol when released from the corresponding monothioacetal in the presence of a reducing agent, such as ascorbic acid.
A new and diastereoselective method for the synthesis of the estrone skeleton from a substituted styrene based on sequential 3-fold use of Cp 2ZrBu 2 (oxidative addition-alkylation and two cyclization-alkylation sequences) and a ruthenium complex catalyzed RC-metathesis of a sterically hindered diene was developed. The prepared estratetraene was obtained in 7 steps from a commercially available starting material and thus the overall synthesis of estrone could be accomplished in 9 steps. Moreover, we have also found that the course of the reaction of substrates bearing the 2-halo-1,7-diene moiety with Cp 2ZrBu 2, i.e., cyclization or oxidative addition to the C-X bond, could be controlled by the nature of the halogen leaving group.
A new modular methodology of preparation of 5-substituted thiophene-2-yl C-nucleosides was developed. A Friedel-Crafts-type of C-glycosidation of 2-bromothiophene with toluoyl-protected methylglycoside 2 gave the desired protected 1beta-(5-bromothiophen-2-yl)-1,2-dideoxyribofuranose 4a in 60%. The key intermediate 4a was then subjected to a series of palladium-catalyzed cross-coupling reactions. The cross-coupling reactions with alkyl organometallics gave beta-(5-alkylthiophen-2-yl)-2-deoxyribonucleosides 4 and 7 in moderate yields accompanied by side-products of reduction. On the other hand, cross-couplings with arylstannanes proceeded smoothly to give a series of beta-(5-arylthiophen-2-yl)-2-deoxyribonucleosides 4 in good yields. Deprotection of toluoylated nucleosides by NaOMe in MeOH and silylated nucleosides by Et 3N.3HF gave a series of free C-nucleosides 6. Alternatively, other types of 5-arylthiophene C-nucleosides 6 were prepared in one step by the aqueous-phase cross-coupling reactions of unprotected 1beta-(5-bromothiophen-2-yl)-1,2-dideoxyribofuranose with boronic acids. Title 5-arylthiophene C-nucleosides 6 exhibit interesting fluorescent properties with emission maxima varying from 339 to 396 nm depending on the aryl group attached.
The Pro-Gly sequence in designed peptides and proteins is often used to mimic natural beta-hairpin turns. Shorter peptides containing this moiety, however, adopt multiple conformations, and their propensity to form the turn is not obvious. In this study, conformational flexibility of Pro-Gly was investigated with the aid of NMR, Raman scattering, and Raman optical activity (ROA). The spectra of a model tetrapeptide NH3+-D-Ala-L-Pro-Gly-D-Ala-CO2- were analyzed on the basis of statistical methods and density functional computations. Other peptide derivatives were adopted as supporting theoretical and experimental models. The results suggest that the loop conformation of the Pro-Gly core is not inherently stable in vacuum. On the other hand, in aqueous environment the propensity to form the beta-hairpin loops is an intrinsic property of the Pro-Gly sequence. It was observed also in a shorter Ac-D-Pro-Gly-NH-Me dipeptide. The attached alanine residues in the tetrapeptide stabilize the structure only partially. Thus an inclusion of the solvent in the calculations is important for correct description of peptide folding in the aqueous environment. The agreement of the optical spectra with the experiment was determined from overlaps between simulated and measured spectral curves. The comparison of the computed NMR, Raman, and ROA was hampered by experimental noise and limited accuracy of the computations. However, the statistical analysis of the spectroscopic data provided conformer distribution consistent with the computation of the relative energies. The combination of the NMR and Raman techniques with the quantum computations appeared very beneficial for the investigation of Pro-Gly conformational behavior, and can be recommended for future peptide folding studies.
- MeSH
- aminokyselinové motivy MeSH
- diferenciální skenovací kalorimetrie MeSH
- difrakce rentgenového záření MeSH
- financování organizované MeSH
- konformace proteinů MeSH
- nukleární magnetická rezonance biomolekulární metody MeSH
- oligopeptidy chemie MeSH
- Ramanova spektroskopie metody MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
