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.     

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.     

Conformational restriction of cyclic dinucleotides with triazole-linked cyclophane analogues

Cyclic dinucleotides (CDN) such as c-di-GMP and c-di-AMP are important multi-functional compounds that regulate a diverse range of processes in bacteria. The diversity of the functions is enabled by the two distinct conformations, that is, open and close conformations. We herein report the concise synthesis of triazole-linked analogues (c-di-GMP^TL, c-di-AMP^TL) through click dimerization of nucleoside analogues. The implementation of a cyclophane system in the central macrocycle furnished the structure with the conformational restriction to maintain the structure similar to the open conformer of natural congeners.     

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.     

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.     

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.     

Synthesis of a novel fluorescent anthryl calix[4]arene as picric acid sensor

A novel and sensitive fluorescence sensor has been designed by click chemistry. Based on the obvious and selective fluorescence quenching of anthryl calix[4]arene, a sensitive and robust platform were developed for visual detection of picric acid (TNP) in the mixture of nitro aromatics. The computational calculations revealed the formation of host–guest complex driven by π–π stacking interactions.     

Multivalent neuraminidase hydrolysis resistant triazole-sialoside protein conjugates as influenza-adsorbents

Triazole-sialoside tailored proteins with high hemagglutinin (HA) and neuraminidase (NA) binding affinity are prepared. Dynamic light scattering shows that these pseudo-sialylated proteins are ideal virus capture macromolecules.     

Synthesis of novel 1,2,3-triazolyl nucleoside analogues bearing uracil, 6-methyluracil, 3,6-dimethyluracil,thymine, and quinazoline-2,4-dione moieties

A series of novel 1,2,3-triazolyl nucleoside analogues was synthesized via the CuAAC reaction of N1-alkynyl uracil, 6-methyluracil, 3,6-dimethyl uracil, thymine and quinazolin-2,4-dione with protected azido β-d-ribofuranose. The obtained compounds differ in both the nature of the pyrimidine-2,4-dione fragment and the length of the polymethylene linker connecting it with the β-d-ribofuranosyl-1,2,3-triazol-4-yl moiety. The 1,2,3-triazolyl nucleoside analogues were evaluated for their cytotoxicity in vitro.     

Synthesis of stemofoline analogues as acetylcholinesterase inhibitors

Thirty-two new stemofoline analogues were prepared from didehydrostemofoline for studies as AChE inhibitors. C-3 Side-chain modified amino, carbamate, triazole and oxazole stemofoline derivatives were prepared. In general the amine derivatives were found to be stronger inhibitors of AChE than their alcohol analogues that we previously reported. Compounds 5 and 26, with small C-3 side-chain substituents, were two of the most active inhibitors. Preliminary molecular docking studies suggested that these compounds may inhibit AChE by binding horizontally along the passage of the active-site gorge and block access to acetylcholine.     

Synthesis and DSSC application of novel dendrimers with benzothiazole and triazole units

Synthesis of novel dendrimers with benzothiazole as surface group and triazole as branching unit is achieved through click chemistry. The presence of more number of benzothiazole and triazole units increases the molar absorption coefficient and alters the fluorescence as well as electrochemical behaviors in the dendrimers. Dye-sensitized solar cell (DSSC) studies reveal that dendrimers with more number of benzothiazole and triazole groups exhibit better current generating capacity than the dendrimers with lesser number of benzothiazole and triazole groups. Dendrimer 2b shows the maximum current conversion efficiency (η) of 7.1%.     

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.     

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.     

Shape persistent hybrid dendrimers from benzene and triazole via ‘click chemistry’

Fully aromatic rigid dendrimers have been synthesized at room temperature based on two different ‘click’-reactions: The dendronization was carried out via the copper catalyzed azide–alkyne Huisgen cycloaddition or Diels–Alder cycloaddition, respectively. The feasible combination of both reactions leads to dendrimer hybrids. Stiff aromatic dendrimers, whose highly nitrogen containing scaffolds are solely based on interconnected benzene and triazole rings, were created.     

Synthesis and anion recognition of a novel oleanolic acid-based cyclic dimer

A novel cyclic dimer based on oleanolic acid was synthesized using click chemistry and it showed remarkable selectivity and affinity to bind fluoride ion through C-H?F hydrogen bond interactions which involved the delocalization of proton in methylene.     

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 sphingomyelin carbon analogues as sphingomyelinase inhibitors

The highly efficient and stereocontrolled syntheses of sphingomyelin carbon analogues 1 and 2 were achieved by effectively utilizing Hofmann rearrangement of enantiomerically pure beta-hydroxyamide 7, which was prepared by an asymmetric hydrogenation of alpha-acyl-gamma-butyrolactone 9 and ring opening with NH(3). Intermediary isocyanate 6 was selectively trapped with the vicinal hydroxy group in an intramolecular fashion to produce an oxazolidinone derivative, 5. In the synthesis of a quite polar compound such as 1, a convenient one-pot procedure of the introduction of a benzyloxycarbonyl group into the hydroxy group resulting from the oxazolidinone ring opening is another key point, because, in addition to the efficiency, this protecting group was easily removable by a simple procedure and workup at the final step. Both synthesized compounds 1 and 2 showed moderate inhibitory activity toward sphingomyelinase from B. cereus.     

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.     

Synthesis and biological evaluation of novel triazole derivatives as antifungal agents

A series of 1-(benzylamino)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-l-yl)propan-2-ols compounds were synthesized and evaluated for their antifungal activities in vitro.The results showed that compounds 6A and 6B exhibited good antifungal activity.Compound 6A8 showed the strongest antifungal activity,which was significantly higher than that of the lead compounds and positive-control drugs Fluconazole and Itraconazole.In particular,the antifungal activity of compound 6A8 against Candida albicans and Candida krusei(MIC80 both at 0.00097μg/mL) was 515 and 64 times that of Fluconazole,respectively.The structure-activity relationships of the synthesized compounds were discussed,and the docking model of the target compounds with fungal lanosterol 14α-demethylase (CYP51) was analyzed.     

CS@Cu2O and magnetic Fe3O4@SiO2-pAMBA-CS-Cu2O as heterogeneous catalysts for CuAAC click reaction

The recovery of agricultural and food wastes are one of the main areas of current research for optimal biowaste management to reduce greenhouse gas (GHG) emissions that are generated when it is not properly treated. Corn silk (CS) as biowaste from the agricultural sector is a rich source of natural compounds especially polysaccharides. We present here a chemical activation method to convert CS to values added heterogeneous catalyst for the synthesis of triazoles compounds via copper catalyzed azide–alkyne cycloaddition (CuAAC) reaction. For this purpose, cuprous oxide coated CS (CS@Cu₂O) and multifunctional Fe₃O₄@SiO₂–para-aminomethyl benzoic acid–CS–Cu₂O composite (denoted as Fe₃O₄@SiO₂‐pAMBA-CS‐Cu₂O) were fabricated. Different analytical techniques have been used to describe the size, crystal structure, elemental composition and other physical properties of the fabricated catalysts. These heterogeneous catalysts showed excellent catalytic activities for the synthesis of 1,4-disubstituted-1,2,3-triazoles via click reaction in H₂O at 70 °C under base and external-reductant-free conditions. The magnetic properties of the catalyst allowed easy separation after reaction by simply applying an external magnet. Other advantages of this work are the recyclability of the catalyst, the absence of reducing agent and base, besides utilisation of bio wastes for the production of heterogeneous catalyst.