Bengamides revisited: new structures and antitumor studies

The structural chemistry and biological activity of the bengamide class of compounds have been further characterized. Extracts prepared from recollected Jaspis cf. coriacea from five sites in Fiji were pooled. Six new bengamides, M (7b), N (8a), O (8b), P (9a), Q (9b), and R (10), were identified, accompanied by the known bengamides A (1a), B (1b), E (3a), F (3b), Y (5), Z (6), L (7a), G (11a), H (11b), and I (12). The structures of the new compounds were determined from spectroscopic data, and some were additionally confirmed by semisynthesis. Cytotoxicity screening data were obtained from the NCI-DTP 60 cell screen for bengamides A, B, and P. Bengamides A and B were more potent than bengamide P, with average IC(50) values of 0.046, 0.011, and 2.70 FM, respectively. The in vitro antitumor activity against MDA-MB-435 human mammary carcinoma was also determined for natural bengamides A, B, E, F, P, M, O, and Z and for synthetic samples of B and O. The best activity was observed for the natural bengamides A (IC(50) = 1 nM) and O (IC(50) = 0.3 nM).     

The Development of a Convergent and Efficient Enantioselective Synthesis of the Bengamides via a Common Polyol Intermediate

An efficient, general synthetic route to the bengamide family of antitumor agents from a common polyol thioester is described. Consecutive aldol condensations afford the protected polyol thioester side chain suitable for coupling to the bengamides. A novel chiral‐phase‐transfer‐catalyzed enantioselective alkylation affords the properly functionalized caprolactams required for the synthesis of more‐complex members of the bengamide family. Use of the methyl 2‐naphthyl ether protecting group, compatible with the boron Lewis acids required for enantioselective aldol condensation, allows direct access to all the bengamides.     

A diversity-oriented synthetic approach to bengamides

A new approach to the bengamides, a new class of antitumor natural products of marine origin, is reported from epoxyamides, prepared by reaction of aldehydes with sulfur ylides. The synthetic strategy has been designed for the delivery of a wide array of analogues. Thus, the terminal alkyl substituent is introduced by a cross olefin metathesis from the corresponding terminal olefin. The combination of cross olefin metathesis, introduction of different nucleophiles by the oxirane ring opening and the introduction of different amines via amide bond formation, can produce a wide array of bengamides analogues.     

Chemoenzymatic synthesis of enantiopure α-substituted cyclohexanones from aromatic compounds

A series of chiral α-substituted cyclohexanones have been synthesized from chemoenzymatically produced chlorocyclohexadienediol. These highly functionalized ketones can be used in the total synthesis of diverse natural products, such as bengamides. A study of the reactivity of α-chlorooxiranes, common intermediates in the synthetic scheme, showed that under nucleophilic opening conditions an intermediate chloroketone may or may not form, depending on the nature of the nucleophiles present in the reaction medium. The stereochemical outcome of this reaction is presented.     

Synthesis and characterization of biologically active new Schiff bases containing 3‐functionalized 1,2,4‐triazoles and their zinc(II) complexes: crystal structure of 4‐bromo‐2‐[(E)‐(1H‐1,2,4‐triazol‐3‐ylimino)‐ methyl]phenol

Biologically active triazole Schiff bases ( L ¹  L ³ ) derived from the reaction of 3‐amino‐1,2,4‐triazole with chloro‐, bromo‐ and nitro‐ substituted salicylaldehydes and their Zn(II) complexes (1–3) have been synthesized and characterized by their physical, spectral and analytical data. Triazole Schiff bases potentially act as tridentate ligands and coordinate with the Zn(II) metal atom through salicylidene‐O, azomethine‐N and triazole‐N. The complexes have the general formula [M(L‐H)₂], where M = zinc(II) and L = ( L ¹ – L ³ ), and observe an octahedral geometry. The Schiff bases and their Zn(II) complexes have been screened for in‐vitro antibacterial, antifungal and brine shrimp bioassay. The biological activity data show the Zn(II) complexes to be more potent antibacterial and antifungal than the parent simple Schiff bases. Copyright © 2011 John Wiley & Sons, Ltd.     

Total syntheses of bengamides B and E

Total syntheses of the cytotoxic marine natural products bengamides B and E are described. Both bengamides are prepared via amide coupling of a protected polyhydroxylated lactone intermediate 9 with a suitably substituted aminocaprolactam intermediate. Lactone 9 is prepared in five steps from commercially available alpha-D-glucoheptonic gamma-lactone. The key reactions are a selective deprotection of a 1,2-acetonide in the presence of a 1,3-acetonide and an (E)-selective olefination of an unstable aldehyde using a gem-dichromium reagent. The bengamide B lactam intermediate 10 is prepared in seven steps from commercially available (5R)-5-hydroxy-L-lysine (12). The desired S-configuration at the gamma-OH lactam position is established using the Mitsunobu reaction.     

Sol–Gel‐Derived Biohybrid Materials Incorporating Long‐Chain DNA Aptamers

Sol–gel‐derived bio/inorganic hybrid materials have been examined for diverse applications, including biosensing, affinity chromatography and drug discovery. However, such materials have mostly been restricted to the interaction between entrapped biorecognition elements and small molecules, owing to the requirement for nanometer‐scale mesopores in the matrix to retain entrapped biorecognition elements. Herein, we report on a new class of macroporous bio/inorganic hybrids, engineered through a high‐throughput materials screening approach, that entrap micron‐sized concatemeric DNA aptamers. We demonstrate that the entrapment of these long‐chain DNA aptamers allows their retention within the macropores of the silica material, so that aptamers can interact with high molecular weight targets such as proteins. Our approach overcomes the major limitation of previous sol–gel‐derived biohybrid materials by enabling molecular recognition for targets beyond small molecules.     

Molecular complexes between π‐excedent heterocycles (indoles and carbazole) and π‐deficient polynitrobenzenes

Five charge‐transfer complexes 1–5 derived from indoles (including a carbazole) and halogenopolynitrobenzenes (ClDNB, FDNB, ClTNB) as well as their individual components have been studied in the solid state by ¹³C CPMAS NMR. The stacking effects on the ¹³C chemical shifts have been rationalized by means of M05‐2X functional and GIAO/B3LYP/6‐311 ++G(d,p) calculations. The results, although only semiquantitative, are very promising for studying such structures. Copyright © 2009 John Wiley & Sons, Ltd.     

Toxicological effects,biological aspects and spectral characterization of organoboron(III) complexes of sulfonamide‐imines

The toxicological effects, biological aspects and spectral characterization of organoboron(III) complexes of sulfonamide‐imines derived by the condensation of salicylaldehyde with different sulfa‐drugs are described. The benzene‐soluble, high‐molecular‐weight complexes have been characterized using a wide range of analytical and spectroscopic techniques, viz. UV, IR, ¹H and ¹¹B NMR. On the basis of these studies, it is inferred that the imines derived from sulfa drugs and salicylaldehyde behave as dibasic tridentate ligands and thus provide a tetrahedral environment around the boron atom. Finally, all these complexes have been screened for their antimicrobial activity against a variety of fungal and bacterial strains and their toxicological effects on male albino rats examined at the dosages employed. Copyright © 2004 John Wiley & Sons, Ltd.     

Ultra‐high performance supercritical fluid chromatography of lignin‐derived phenols from alkaline cupric oxide oxidation

Traditional chromatographic methods for the analysis of lignin‐derived phenolic compounds in environmental samples are generally time consuming. In this work, an ultra‐high performance supercritical fluid chromatography method with a diode array detector for the analysis of major lignin‐derived phenolic compounds produced by alkaline cupric oxide oxidation was developed. In an analysis of a collection of 11 representative monomeric lignin phenolic compounds, all compounds were clearly separated within 6 min with excellent peak shapes, with a limit of detection of 0.5–2.5 μM, a limit of quantification of 2.5–5.0 μM, and a dynamic range of 5.0–2.0 mM (R² > 0.997). The new ultra‐high performance supercritical fluid chromatography method was also applied for the qualitative and quantitative analysis of lignin‐derived phenolic compounds obtained upon alkaline cupric oxide oxidation of a commercial humic acid. Ten out of the previous eleven model compounds could be quantified in the oxidized humic acid sample. The high separation power and short analysis time obtained demonstrate for the first time that supercritical fluid chromatography is a fast and reliable technique for the analysis of lignin‐derived phenols in complex environmental samples.     

Aminopolyols from Carbohydrates: Amination of Sugars and Sugar‐Derived Tetrahydrofurans with Transaminases

Carbohydrates are the major component of biomass and have unique potential as a sustainable source of building blocks for chemicals, materials, and biofuels because of their low cost, ready availability, and stereochemical diversity. With a view to upgrading carbohydrates to access valuable nitrogen‐containing sugar‐like compounds such as aminopolyols, biocatalytic aminations using transaminase enzymes (TAms) have been investigated as a sustainable alternative to traditional synthetic strategies. Demonstrated here is the reaction of TAms with sugar‐derived tetrahydrofuran (THF) aldehydes, obtained from the regioselective dehydration of biomass‐derived sugars, to provide access to cyclic aminodiols in high yields. In a preliminary study we have also established the direct transamination of sugars to give acyclic aminopolyols. Notably, the reaction of the ketose d ‐fructose proceeds with complete stereoselectivity to yield valuable aminosugars in high purity.     

Metal–Organic Framework (MOF)‐Derived Nanoporous Carbon Materials

Metal–organic framework (MOF)‐derived nanoporous carbon materials have attracted significant interest due to their advantages of controllable porosity, good thermal/chemical stability, high electrical conductivity, catalytic activity, easy modification with other elements and materials, etc. Thus, MOF‐derived carbons have been used in numerous applications, such as environmental remediations, energy storage systems (i.e. batteries, supercapacitors), and catalysts. To date, many strategies have been developed to enhance the properties and performance of MOF‐derived carbons. Herein, we introduce and summarize recent important approaches for advanced MOF‐derived carbon structures with a focus on precursor control, heteroatom doping, shape/orientation control, and hybridization with other functional materials.     

Photosensitizing Activity of Endogenous Eye Lens Chromophores: An Attempt to Unravel Their Contributions to Photo‐Aging and Cataract Disease

UVA‐visible light has been proposed as a risk factor in the photo‐aging of the human eye lens, as well as in the etiology of cataract disease. There is accumulating evidence indicating that photosensitizing reactions mediated by endogenous chromophores, which are generated during human eye lens aging, can play an important role in the generation of these processes. These reactions can lead to protein impairment by inducing non‐enzymatic post‐translational modifications such as protein oxidation and crosslinking. Although numerous chromophores have been characterized as both bound to human eye lens proteins and as unbound low‐molecular‐mass compounds, their contribution to eye lens photoaging and cataract disease is not completely understood. In this article we discuss the photochemical contribution of UV‐filters derived from tryptophan catabolism and advanced glycation end products (AGEs) to human eye lens aging and cataract disease. We also discuss the recently described photosensitizing capacity of chromophores derived from newly discovered glucose and ascorbate degradation as a parallel pathway to their role in AGEs generation.     

Preparation and Isolation of a Chiral Methandiide and Its Application as Cooperative Ligand in Bond Activation

The activation of element–hydrogen bonds by means of metal–ligand cooperation has received increasing attention as alternative to classical activation processes, which exclusively occur at the metal center. Carbene complexes derived from methandiide precursors have been applied in this chemistry enabling the activation of a series of E?H bonds by addition reactions across the M?C bond. However, no chiral carbene complexes have been applied to realize stereoselective transformations to date. Herein, we report the isolation and structure elucidation of an enantiomerically pure dilithiomethane, which could be prepared by direct double deprotonation. The obtained dilithium salt was used for the preparation of the first chiral methandiide‐derived carbene complex, which was applied in stereoselective cooperative S?H bond activation.     

Orange Peel Derived C‐dots Decorated CuO Nanorods for the Selective Monitoring of Dopamine from Deboned Chicken

A novel electrode based on orange peel derived C‐dots decorated CuO nanorods (CR@C‐dot) modified lead pencil (LP) electrode has been fabricated for highly sensitive and selective monitoring of dopamine (DA). Prior to the functionalization with C‐dot, electrochemical efficacy of CR was evaluated and compared with CuO nano‐needles (CN) and nano‐spheres (CS). The morphology, surface area and composition of synthesized nanoparticles was confirmed through field emission scanning electron microscopy (FE‐SEM), N₂‐adsorption‐desorption isotherm, X‐ray diffraction (XRD), Raman spectroscopy and X‐ray photoelectron spectroscopy (XPS). Our results indicated that CR has high electrocatalytic activity compared to CN and CS by expositing greater fraction of catalytic active sites, large surface area and short diffusion pathways. The electrochemical efficacy of CR is further enhanced by decorating with orange peel derived C‐dots, which surprisingly lead to the integrations of surface‐active sites with current collectors with minimum resistance by acting as an electron transport mediator and providing more surface defects. The developed CR@C‐dot sensor enables highly sensitive and selective recognition of DA detection (0.0007 μM), over good linear range (5–2250 μM) with rapid response time. the developed CR@C‐dot sensor was successfully used to monitor the DA from deboned chicken, thus suggesting reliability of the developed electrode.     

Spectroelectrochemical Sensing Based on Multimode Selectivity Simultaneously Achievable in a Single Device. 19. Preparation and Characterization of Films of Quaternized Poly(4‐vinylpyridine)‐silica

Quaternized poly(4‐vinylpyridine) (QPVP) has been incorporated as an anion exchanger into sol‐gel derived silica films for use in a spectroelectrochemical sensor. The preparation, characteristics and performance of these films are described. The films, which are spin‐coated onto the surface of a planar optically transparent electrode, are optically transparent and uniform. Scanning electron microscopy and spectroscopic ellipsometry have been used to examine film structure, thickness and optical properties. These films have been shown both spectroscopically and electrochemically to preconcentrate ferrocyanide, a model analyte for the sensor. The films can be regenerated for multiple measurements by exposure to 1 M KNO₃. The effects of polymer molecular weight and storage conditions on film performance are described. The overall response of this film is comparable to the poly(dimethyldiallylammonium chloride)‐silica films previously used for this sensor.     

Metabolic profiling of tenacigenin B,tenacissoside H and tenacissoside I using UHPLC‐ESI‐Orbitrap MS/MS

Marsdenia tenacissima, which is widely used as an anticancer herb in traditional Chinese medicine, has been shown to possess anticancer activity. However, its metabolic profile is poorly investigated. Tenacigenin B is the major steroidal skeleton of C‐21 steroids in M. tenacissima. Tenacissoside H and Tenacissoside I are detected at relatively high levels in M. tenacissima. Therefore, we studied their metabolic characteristics in human liver microsomes by ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry. Fourteen metabolites were tentatively identified by accurate mass measurement and MS/MS fragmentation behavior. It was found that hydroxylation reactions were the major metabolic pathway of Tenacissoside H and Tenacissoside I in human liver microsomes, whereas the metabolic pathway of Tenacigenin B involved dehydrogenation reactions. This is the first time that the metabolic profile of C‐21 steroids from M. tenacissima has been explored in human liver microsomes, which is of great significance for subsequent pharmacokinetic and interaction research. Biotransformation in vivo or in vitro may influence the structure of a compound and change its activity. Identification of their fragmentation behaviors and metabolites provides valuable and new information for further understanding the anti‐tumor activity of M. tenacissima. Copyright © 2016 John Wiley & Sons, Ltd.     

Recent Advances in the Chemistry of N‐Heterocyclic‐Carbene‐Functionalized Metal‐Nanoparticles and Their Applications

Metal‐nanoparticles (M‐NPs) have been widely applied in catalysis, imaging, sensing and medicine. One particularly active area of this research is the modification of the surface of the nanoparticles to prevent aggregation through the coordination of ligands. N‐Heterocyclic carbenes (NHCs) have emerged as suitable ligands for this purpose due to their affinity to the metals and their strongly electron donating nature. A number of rationally designed NHC‐modified M‐NPs have been developed using strategies based on metal complex decomposition and ligand exchange. Herein, NHC‐stabilized M‐NPs based on a range of transition metals, especially the recent advances, were summarized.     

Study of Nanocrystalline BiMnO3‐‐PbTiO3: Synthesis,Structural Elucidation,and Magnetic Characterization of the Whole Solid Solution

In the last ten years, the study and the search for new multiferroic materials have been a major challenge due to their potential applications in electronic technology. In this way, bismuth‐containing perovskites (BiMO₃), and particularly those in which the metal M position is occupied by a magnetically active cation, have been extensively investigated as possible multiferroic materials. From the point of view of synthesis, only a few of the possible bismuth‐containing perovskites can be prepared by conventional methods but at high pressures. Herein, the preparation of one of these potential multiferroic systems, the solid solution xBiMnO₃‐(1?x)PbTiO₃ by mechanosynthesis is reported. Note that this synthetic method allows the oxides with high x values, and more particularly the BiMnO₃ phase, to be obtained as nanocrystalline phases, in a single step and at room temperature without the application of external pressure. These results confirm that, in the case of Bi perovskites, mechanosynthesis is a good alternative to high‐pressure synthesis. These materials have been studied from the point of view of their structural characteristics by precession electron diffraction and magnetic property measurements.     

Cyclodextrin‐Templated Porphyrin Nanorings

α‐ and β‐Cyclodextrins have been used as scaffolds for the synthesis of six‐ and seven‐legged templates by functionalizing every primary CH₂OH with a 4‐pyridyl moiety. Although these templates are flexible, they are very effective for directing the synthesis of macrocyclic porphyrin oligomers consisting of six or seven porphyrin units. The transfer of chirality from the cyclodextrin templates to their nanoring hosts is evident from NMR and circular dichroism spectroscopy. Surprisingly, the mean effective molarity for binding the flexible α‐cyclodextrin‐based template within the six‐porphyrin nanoring (74 M ) is almost as high as for the previously studied rigid hexadentate template (180 M ). The discovery that flexible templates are effective in this system, and the availability of a template with a prime number of binding sites, open up many possibilities for the template‐directed synthesis of larger macrocycles.