Synthesis of novel analogues of zanamivir as neuraminidase inhibitors

<正>A versatile synthesis of novel zanamivir analogues modified at C-4 and C-8 positions was described.The formation of amides from the acid with corresponding amines,followed by click chemistry generated the triazole substituted compounds as novel analogues of neuraminidase inhibitors in good yields.     

A novel BINOL-based cyclophane via click chemistry: synthesis and its applications for sensing silver ions

A novel BINOL-based cyclophane 1 incorporating two triazole moieties was synthesized via click chemistry and characterized. Among the metal ions screened, only Ag⁺ was found to have the ability to quench the fluorescence of 1 in methanol solution. The 1:1 binding mode of 1-Ag⁺ was confirmed. The competitive experiment showed that compound 1 can be used as a specific fluorescent sensor for Ag⁺ over a wide range of competing cations.     

Synthesis of dinucleotides with 2′-C to phosphate connections by ring-closing metathesis

Four different nucleosides with olefinic 2′-modifications were prepared; 2′-C-methylene, 2′-C-(propen-1-yl), 2′-C-allyl and 2′-O-allyl uridines, respectively. These were incorporated into dinucleotides with allyl phosphate or vinyl phosphonate linkages. Hence, six different dinucleotides were studied as substrates for RCM reactions, and from four of these, cyclic dinucleotides with connections between 2′-C and phosphorus of 3-6 atoms were obtained.     

One-pot synthesis of triazole-linked glycoconjugates

Highly efficient one-pot synthesis of 1,2,3-triazole-linked glycoconjugates was presented involving a Cu(I) catalyzed 1,3-dipolar cycloaddition as the key step. It offers a convenient route to prepare neoglycoconjugates derived from unprotected saccharides or peracetylated saccharides.     

Synthesis of steroidal dendrimers modified by ‘click’ chemistry with PAMAM dendrons as unimolecular micelles

Novel Fréchet–PAMAM hybrid dendrimers linked by triazole units as unimolecular micelles with a hydrophobic core surrounded by a hydrophilic shell were prepared. The dendritic cores with 3 and 6 alkyne terminal groups were synthesized from 1,3,5-tribromomethyl-benzene (tBrMeB), in one case by direct coupling with 17α-ethynylestradiol (EE); in the second one the tBrMeB was reacted with bis(hydroxymethyl) phenol followed by chlorination of the hydroxyl groups and subsequent coupling to EE. With this strategy, the core can be grown by further substitutions of bis(hydroxymethyl) phenol over the halogenated terminals as Fréchet dendrimer. The hydrophilic shells used were PAMAM type dendrons of 0.5 and 1.5 generations with azide as focal point and tert-butyl ester as end groups. The unimolecular micelles were obtained by cycloaddition between an azide in the selected dendron and the alkyne terminal in the hydrophobic core to obtain a 1,4-disubstituted 1,2,3-triazole. Once the coupling was achieved, the tert-butyl ester groups were hydrolyzed in trifluoroacetic acid and the corresponding dendrimers with carboxylic acid as end groups were completely soluble in phosphate buffer solutions of pH 7.0, 7.4, and 8.0. All hybrid dendrimers were characterized by High Resolution Mass Spectrometry, ¹H and ¹³C NMR, and FTIR.     

Microwave-assisted synthesis of a triazole-linked 3′-5′ dithymidine using click chemistry

Synthesis of a triazole-linked 3′-5′ thymidine dimer making use of 1,3-dipolar cycloaddition is described. The azido-precursor was obtained by regioselective chlorination of thymidine, followed by azidation. The second precursor, a propargyl derivative, was obtained by selective 3′-O-alkylation of thymidine. Two ‘click systems’ were compared to obtain the desired dimer. These reactions were performed by microwave irradiation.     

Convergent synthesis of oligomers of triazole-linked DNA analogue (DNA) in solution phase

A convergent route for the solution-phase synthesis of oligomeric triazole-linked analogues of DNA (^TLDNA) has been developed. A one-pot procedure for desilylation of masked acetylene and the ensuing copper-catalyzed Huisgen coupling reaction between oligomers allowed the solution-phase synthesis of 7-mer and 8-mer ^TLDNA in good yield.     

Microwave assisted synthesis of triazolobenzoxazepine and triazolobenzoxazocine heterocycles

Intramolecular click chemistry was utilized to effect synthesis of the benzofused, triazole ring systems. The trimethylsilyl group was found to impede the reaction progress, and therefore, conditions employing in situ removal of the TMS group coupled with microwave irradiation give the penultimate targets with good conversion.     

Separation of inorganic anions on a triazole-functionalized ion exchanger in ion chromatography

The retention behavior of inorganic anions on a triazole-based stationary phase was first examined in ion chromatography. It was initially designed for hydrophilic interaction liquid chromatography and was simply prepared by introducing the triazole groups onto the surface of silica gel via click chemistry. Effective separation of common inorganic anions, including iodate, chloride, bromide, nitrate and iodide, was achieved with Na(2)SO(4) eluent. The logarithm of the retention factor of analytes was observed to be linear with the logarithm of the eluent concentration, and the slopes of the plots were almost the same as those of the ideal theoretical value. The eluent pH value in the range of 3.4-7.0 had little effect on the separation. The utility of the column was demonstrated for the determination of UV-absorbing anions in saliva and tap water.     

Efficient and tunable synthesis of new polydentate bifunctional chelating agents using click chemistry

Two novel bifunctional chelating agents, which are bistriazole-based polyaminocarboxylic acids, have been designed and synthesised in high yields. An elegant synthetic approach using the Cu-catalysed azide-alkyne cycloaddition has been developed. This convenient route could be employed for the synthesis of a variety of polydentate bifunctional chelators.     

Synthesis of novel 1,4-disubstituted-1,2,3-triazole semi synthetic analogues of forskolin by click reaction

New 1,4-disubstituted-1,2,3-triazole analogues of forskolin (5a-g, 6a-g) have been prepared by regioselective propargylation at 1-position followed by Cu(I) catalysed cycloaddition of different alkyl azides under the click reaction conditions. An interesting acyl shift in the base catalysed propargylation afforded a new series of 1,4-disubstituted-1,2,3-triazole analogues of forskolin (6a-g). These analogues have potential selective therapeutic applications as antihypertensive, antiglaucoma, antiasthma and antiobesity agents.     

Halide binding and self-assembling behavior of Triazole-based acyclic and cyclic molecules

The present study demonstrates the use of triazole moiety in designing molecules endowed with the ability for self-assembly and molecular recognition. The receptors 7a and 9a having open structures bind to fluoride ion with good affinity. Various cyclophanes with 19-, 20-, 21-, 38-, and 40-membered rings containing triazole units were designed and synthesized. X-ray crystal structure of macrocycle 16 showed a tubular like architecture. Triazolophane 22 possesses bifurcated CH?N intramolecular hydrogen bonds and it further organizes in the solid state using CH?N interactions. Triazole based compounds are potential store house for exploiting CH?O and CH?N hydrogen bonding interactions for molecular self-assembly.     

Fixed-charge labels for simplified reaction analysis: 5-hydroxy-1,2,3-triazoles as byproducts of a copper(I)-catalyzed click reaction

High-resolution multistage mass spectrometric studies of isotope-labelled derivatives of a fixed-charge labelled sugar triazole assisted the identification of 5-hydroxy-1,2,3-triazoles as byproducts of the copper(I)-catalyzed cycloaddition of azides and terminal alkynes. Reaction optimization with inclusion of the auxiliary ligand, tris(benzyltriazolylmethyl)amine furnished an improved ligation protocol in which formation of the 5-hydroxytriazole is mitigated.     

Conformational features of linear and cyclic enkephalins. A computational study

A theoretical conformational study using the CICADA program package (J. Mol. Struct. (Theochem), 337 (1995) 17) was performed for two linear enkephalins, Leu-enkephalin and Met-enkephalin, and two cyclic analogues, DLFE and DPDPE. The conformational flexibilities of whole molecules and selected torsions were calculated.

The low energy conformers obtained were compared with structures obtained by spectroscopic methods. The mutual space positions of key elements for receptor recognition were analyzed. Conformations were clustered using RMS deviation computed for selected atoms. The different conformational behavior of aromatic rings in cyclic analogues of enkephalins was observed. While aromatic rings of cyclic analogues exhibit different conformational behavior, the linear enkephalins show similar behavior in these key parts.

Hydrogen bonds predicted by spectroscopic measurements were confirmed by our calculations. Also very specific conformational features, like concerted conformational movement, were analyzed.     

An efficient one-pot synthesis of C2-symmetric triazolophanes by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction

A facile and efficient one-pot synthesis of 12-15-membered triazolophanes has been accomplished using CuAAC methodology. The formation of triazolophanes was confirmed by spectral analysis and the products were isolated in good yield. The effect of solvents on this reaction was also studied.     

Synthesis of triazole analogues of the nanaomycin antibiotics using ‘click chemistry’

A series of triazole analogues of the nanaomycin family of antibiotics have been prepared using a ‘click’ dipolar cycloaddition of a naphthalene azide to various alkynes, followed by oxidation to the desired pyranonaphthoquinones.     

Conformational Study of Glycal-Type Neuraminidase Inhibitors

The conformational flexibility of two glycal-type neuraminidase inhibitors has been studied, using several molecular modeling techniques. In agreement with the experimental data available, an intramolecular hydrogen bond, representing a key structural feature that controls the conformer distribution in solution, has been identified. The contribution of each substituent to the overall equilibrium was evaluated using simplified derivatives. Additionally, four methods for estimating NMR coupling constants from dihedral angles were evaluated and the Haasnoot method was found to be appropriate for this class of sugars. These results should allow a better understanding of the structural parameters governing physico-chemical properties of glycal-like compounds. Supplemental materials are available for this article. Go to the publisher's online edition of Journal of Carbohydrate Chemistry to view the free supplemental file.     

Design and Synthesis of 1-Glycosyl-4-{N-[(2'-morpholinethoxy)-phenyl]aminomethyl}-1H-1,2,3-triazoles as Calcium Activators

A series of novel 1-glycosyl-4-{N-[(2'-morpholinethoxy)phenyl]aminomethyl}-1H-1,2,3-triazoles was designed and synthesized through a simple and efficient multistep synthetic method in good yields. The 1,2,3-triazole moiety acted as a single disubstituted ring and a linker between carbohydrates(D-glucose, D-galactose, maltose and lactose) and morpholine. The compounds were characterized by ¹H NMR, ¹³C NMR and mass spectra(MS). Two different deprotection methods were discussed. The effects of compounds 5a, 5c and 6e on the intracellular calcium ion concentration([Ca²⁺]_i) in the central neurons of S. exigua were well investigated by calcium imaging technique. The results demonstrated that compound 6e could elevate the calcium concentration in the glial cells, not in the neurons.     

A Simple and Convenient Strategy for the Synthesis of Tolanophanes: Synthesis,Characterization and Conformational Analysis of a Novel Tolanophane

The bromination/dehydrobromination of stilbenophanes as a practical, simple and efficient strategy is applied to the synthesis of tolanophanes 1a (n = 2) and 1b (n = 4). The method is significantly superior to the reported methods. A careful conformational study on a novel tolanophane 1b showed that the relative stability of its conformers is directly linked to both twist angle between the two arene rings and the orientation of the alkoxy groups. The strong interaction between 1b and CDCl₃ at ? 60°C is an unusual feature that is attributed to high restriction in its molecular motion.     

Design and Synthesis of New Bile AcidSterol Conjugates Linked via 1,2,3‐Triazole Ring

A new steroid conjugates have been obtained from bile acids and sterol derivatives using ‘click chemistry’. Intermolecular 1,3‐dipolar cycloaddition of the propargyl ester of bile acids (lithocholic, deoxycholic, and cholic acid) and azide derivatives of sterols (ergosterol and cholesterol) gave a new bile acid? sterol conjugates linked with a 1,2,3‐triazole ring. The structures of all products were confirmed by spectroscopic (¹H‐ and ¹³C‐NMR, and FT‐IR) analyses, mass spectrometry (ESI‐MS), and in silico biological activity evaluation methods (PASS), as well as PM5 semiempirical methods.