Synthesis and characterisation of tetra-tetrazole macrocycles

The syntheses of tetra-tetrazole macrocycles, containing two bis-tetrazole units linked by a variety of alkyl-chain lengths from four to eight carbons, are described. The crystal structures of three of these derivatives are reported, and the molecular conformation in the solid state is compared to that of the previously reported tetra-tetrazole macrocycle and to other bis- and tris(tetrazole)benzene structures. The macrocycle conformation is influenced by the length of the alkyl-chain linker, the relative orientation of the tetrazole rings on the benzene ring and by intermolecular interactions. In the macrocycles based on 1,2-bis(tetrazole)benzene, the adjacent tetrazole rings on the benzene ring are prevented from becoming co-planar on intramolecular (steric) grounds. In the 1,3- and 1,4-bis(tetrazole)benzene derivatives, there is no such impediment, and a co-planar arrangement is observed where intra- and/or intermolecular stacking interactions exist. Deviations from co-planarity are associated with optimisation of intermolecular interactions between the tetrazole rings and adjacent alkyl chains. In the macrocycle based on 1,4-bis(tetrazole)benzene with four-carbon linkers, an intramolecular stacking interaction exists, which precludes the presence of any cavity. In the macrocycle based on 1,3-bis(tetrazole)benzene with six-carbon linkers, a cavity of 10.8×9.4 Å is observed for each molecule in the solid state, although the packing of adjacent molecules is such that there are no extended channels running through the crystal.     

Synthesis of macrocycles containing 1,3,4-oxadiazole and pyridine moieties

A series of peptide-like 25–28 membered macrocycles containing 1,3,4-oxadiazoles and pyridines bearing a chiral center scaffold have been synthesized by using known coupling reagents and common protecting groups. The yield of the purified macrocycles was poor on an average, yet it seems to be independent of amino acid substitution or stereochemistry. These macrocycles represent a new class of structures for further development and for future application in high-throughput screening against a variety of biological targets.     

Synthesis and chiroptical properties of two new planar-chiral macrocycles

Could simple intraannular-arm macrocyclic systems exist in enantiopure stable forms? The effective synthesis of two representative compounds of such a class, their resolution into enantiomers, and experiments justifying their stability toward racemization are presented.     

Synthesis and characterisation of macrocycles containing both tetrazole and pyridine functionalities

The syntheses of tetra-tetrazole macrocycles containing at least one 2,6-bis(tetrazole)pyridine unit, linked by a variety of n-alkyl (n=3, 5, 7 or 9 carbon atoms) chain lengths, are described. There has been no previous incorporation of the pyridine moiety into a tetra-tetrazolophane macrocycle. The crystal structure of one such tetra-tetrazole macrocycle has also been structurally characterised and revealed a bowl-shaped conformation.     

Synthesis, characterization and crystal structure of a novel 3D network triorganotin(IV) polymer containing two types of macrocycles

A novel triorganotin(IV) complex 1 has been synthesized and structurally characterized by elemental analysis, FT-IR, NMR (¹H, ¹¹⁹Sn) spectra and X-ray crystallography. This complex displays a 3D network structure, which contains two types of chair form macrocycles.     

Synthesis of nano-scale shape-persistent macrocycles via hydrogen bonding-promoted formation of amide and hydrazone bonds

This paper describes the synthesis of two series of rigid macrocycles from hydrogen bonding-induced folded aryl amide and hydrazone oligomers that bear two amines or one amine and one aldehyde. The diamines reacted with diacyl chloride to produce amide macrocycles, whereas the latter underwent self-coupling reactions to afford imine macrocycles. DFT calculations revealed that the new macrocycles possess rigid planar conformations and their cavity diameters were estimated to be 1.86 nm–2.75 nm.     

Chiral macrocycles,part I: Synthesis and enantioselective transport of carboxylic acids as their Li+ salts

A new series of tetrapyrazolic macrocycles with a functionalized sidearm has been prepared. Their capability to transport Li⁺ salts of carboxylic acids has been examined and is shown to be strongly dependent on the functionality of the macrocycle sidearm. In the case of the Li⁺ (D, L.)-mandelate, chiral recognition has been observed.     

Synthesis and properties of novel photochromic bisthienylethenes containing imidazole and imidazolium derivatives

A series of bisthienylethenes containing imidazole and imidazolium derivatives have been prepared and the products have been characterized by means of NMR and MS.Their photochromic and fluorescent switch properties have been investigated by UV–vis absorption spectra and fluorescence spectra.The fluorescent emissions of these kinds of photochromic compounds can be simply modulated by varying the imidazole groups,which shows that these compounds may have potential application in the design of fluorescent photochromic materials.     

Synthesis and metalation of novel fluorescent conjugated macrocycles

[reaction: see text] Large shape-persistent conjugated macrocycles with tunable pore diameters in the nanometer regime were prepared by a simple, one-pot procedure. These new self-assembled macrocycles contain rings of 48-66 covalently bonded atoms and can bind multiple metal ions, forming soluble luminescent complexes.     

Novel imidazole derivatives as antifungal agents: Synthesis,biological evaluation,ADME prediction and molecular docking studies

Abstract

A series of 2-(substituteddithiocarbamoyl)-N-[4-((1H-imidazol-1-yl)methyl)phenyl]acetamide derivatives was designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. All synthesized compounds were characterized by IR, ¹H-NMR, ¹³C-NMR, and HRMS spectra and elemental analyses. Antifungal activity tests were performed against four different fungal strains. Molecular docking studies were performed to investigate the mode of action towards the fungal lanosterol 14α-demethylase, a cytochrome P450-dependent enzyme. ADME studies were carried out and a connection between activities and physicochemical properties of the target compounds was determined. Most of the final compounds exhibited significant activity against Candida albicans and Candida krusei with MIC₅₀ value 12.5?μg/mL. The results of in vitro anti-Candida activity, a docking study and ADME prediction revealed that the newly synthesized compounds have potential anti-Candida activity and evidenced the most active derivative, 5b (2-Pyrrolidinthiocarbonylthio-N-[4-((1H-imidazol-1-yl)methyl)phenyl]acetamide), which can be further optimized as a lead compound.     

Synthesis and characterization of some novel aromatic polyimides

Three new diamines 1,2-di(p-aminophenyloxy)ethylene, 2-(4-aminophenoxy)methyl-5-aminobenzimidazole and 4,4-(aminopheyloxy) phenyl-4-aminobenzamide were synthesized and polymerized with 3,3′,4,4′-benzophenone tetracarboxylic acid dianhydride (BP), 4,4′-(hexafluoroisopropyledene)diphthalic anhydride (HF) and 3,4,9,10-perylene tetracarboxylic acid dianhydride (PD) either by one step solution polymerization reaction or by two step procedure. The later includes ring opening poly-addition to give poly(amic acid), followed by cyclodehydration to polyimides with the inherent viscosities 0.62-0.97 dl/g. Majority of polymers are found to be soluble in most of the organic solvents such as DMSO, DMF, DMAc, m-cresol even at room temperature and few becomes soluble on heating. The degradation temperature of the resultant polymers falls in the ranges from 240 °C to 550 °C in nitrogen (with only 10% weight loss). Specific heat capacity at 300 °C ranges from 1.1899 to 5.2541 J g⁻¹ k⁻¹. The maximum degradation temperature ranges from 250 to 620 °C. T_g values of the polyimides ranged from 168 to 254 °C.     

Synthesis and characterization of a novel imidazole cyclic trimer

A novel cyclic trimer of imidazole 1, in which imidazole rings are connected by amide bonds, has been synthesized with the help of LiCl as a template for the cyclization. The absorption spectra of 1 indicate the extension of conjugation between imidazole rings and amide bonds. The addition of 3 M equiv of MgCl₂ solubilizes 1 in polar organic solvent, suggesting the chelating ability of 1 to Mg cation.     

Synthesis and biological evaluation of novel derivatives of desloratadine

Series of novel derivatives of desloratadine designed as arginine vasopressin receptor antagonists were synthesized and structurally characterized by melting points,~1H NMR and HRMS.Their in vivo diuretic activities were evaluated on rats,and several target compounds showed promising diuretic results, especially compounds 8,18,27 and 31.Further in vitro bonding assay and cAMP assay showed that these compounds had a higher affinity to vasopressin V2 receptor than VI a receptor.Our studies indicated that desloratadine may be an active substructure for novel arginine vasopressin receptor antagonist development.     

Synthesis and biological evaluation of novel steroid-linked nitrogen mustards

Two novel steroid-linked nitrogen mustard conjugates 1a and 1b were synthesized by using estrogenic acid 4 coupled with aniline mustard 8 and phenol mustard 13 in an esterification or amidation procedure. Preliminary cytotoxic screening on cancer cell lines in vitro showed that, the steroid-ester linked nitrogen mustard conjugate la exhibited obvious increasing of activities.     

Synthesis and biological evaluation of novel macrocyclic paclitaxel analogues

[reaction: see text] This work describes the synthesis of two novel macrocyclic taxoid constructs by ring-closing olefin metathesis (RCM) and their biological evaluation. Computational studies examine conformational profiles of 1 and 2 for their fit to the beta-tubulin binding site determined by electron crystallography. The results support the hypothesis that paclitaxel binds to microtubules in a "T" conformation.     

A simple and efficient synthesis of boron-imidazole macrocycles and their crystal structures

A simple and selective method for the synthesis of boron-imidazole macrocycles is described and their X-ray structures are presented.     

Synthesis and biological evaluation of novel fumagillin and ovalicin analogues

A promising approach among the numerous efforts to cure cancer is the interruption of the tumour-induced formation of new blood vessels (angiogenesis). By suppressing angiogenesis with drugs, the tumour can neither grow to a life threatening size, nor metastasize. The natural product fumagillin 1 and the structurally related ovalicin 2 are two of the most potent anti-angiogenic compounds. Here, we report the design and synthesis of novel fumagillin and ovalicin analogues lacking reactive epoxy functionalities, which were thought to be responsible for the severe toxic side-effects observed. We also report a new synthetic approach and the determination of the anti-angiogenic properties of these compounds in endothelial cells.     

Synthesis and biological evaluation of novel benzoxazinic analogues of ellipticine

Original 1,4-benzoxazine analogues of ellipticine were prepared using a general synthetic route that relied on an anionic ring annulation as the key transformation. The interest of this approach lies on the possibility of an easy entrance to a wide range of derivatives from the phenol intermediate. In addition, this synthetic strategy offers a smart access to diverse structurally related heteroaryl annulated carbazole analogues of ellipticine just by replacing the starting heterocyclic core. Antiproliferative activities of newly synthesized derivatives were evaluated toward tumor cell lines.     

Synthesis and biological evaluation of novel cyanuric acid-tethered tris-pyridinium derivatives

1. Download : Download high-res image (74KB)
2. Download : Download full-size image