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Hydroxylation of aryl carbon-hydrogen bonds with transition metal catalysts has proven challenging when oxygen is used as the oxidant. Here, we report a palladium complex bearing a bidentate pyridine/pyridone ligand that efficiently catalyzes this reaction at ring positions adjacent to carboxylic acids. Infrared, x-ray, and computational analysis support a possible role of ligand tautomerization from mono-anionic (L,X) to neutral (L,L) coordination in the catalytic cycle of aerobic carbon-hydrogen hydroxylation reaction. The conventional site selectivity dictated by heterocycles is overturned by this catalyst, thus allowing late-stage modification of compounds of pharmaceutical interest at previously inaccessible sites., Competing Interests: Competing interests: US Patent application 63/124,544 is pending.

To date, no fused heterocycles have been formed on folic acid molecules; for this reason, and others, our target is to synthesize new derivatives of folic acid as isolated or fused systems. Folic acid 1 reacted with ethyl pyruvate, triethyl orthoformate, ethyl chloroformate, thioformic acid hydrazide, and aldehydes to give new derivatives of folic acid 2 - 6a , b . Moreover, It reacted with benzylidene malononitrile, acetylacetone, ninhydrin, ethyl acetoacetate, ethyl cyanoacetate, and ethyl chloroacetate to give the pteridine fused systems 10 - 15 , respectively. Ethoxycarbonylamino derivate 5 reacted with some nucleophiles containing the NH 2 group, such as aminoguanidinium hydrocarbonate, hydrazine hydrate, glycine, thioformic acid hydrazide, and sulfa drugs in different conditions to give the urea derivatives 16 - 20a , b . Compound 4 reacted with the same nucleophiles to give the methylidene amino derivatives 21 - 24a , b . The fused compound 10 reacted with thioglycolic acid carbon disulfide, malononitrile, and formamide to give the four cyclic fused systems 25 - 30 , respectively. The biological activity of some synthesized showed moderate effect against bacteria, but no effect shown towards fungi.

The present paper reported a biomimetic synthesis of mesoporous silicas (BMSs) at room temperature by using synthesized polymers (C 16 -l-His, C 16 -l-Pro and C 16 -l-Trp) which derived from amino acid with ring structures as template under basic condition via co-structural-directing-agent method. The formation mechanism of BMSs and effect of initial synthesis conditions (such as surfactant structure, pH and co-solvents) on morphology and structure of BMSs were systematically studied. Synthesized BMSs were characterized by transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and nitrogen adsorption/desorption isotherms. The results showed that the surfactant structure was the dominant factor to direct the final mesostructure of BMSs, since the structure of surfactant affected the structure and size of clusters. Meanwhile the generation of BMSs required very rigorous alkaline condition which controlled the ionization degree of the surfactant and thus contributing to adequate stacking energy. Higher pH resulted in construction of channels with higher curvature. The presence of ethanol was found to facilitate the formation of BMSs with larger particle size. In application, aspirin can be loaded into BMSs with high efficiency, and the drug crystalline state of aspirin transformed from crystalline state to amorphous state during this process, which undoubtedly lead to the improvement of drug dissolution from 72.8% to 100% within 90 min. It is convincible that the biomimetic method presented here provided novel insight on precisely control of mesoporous silica and undoubtedly promoted the application of mesoporous silica materials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A series of new benzimidazolium halides were synthesized in good yields as unsymmetrical N -heterocyclic carbene (NHC) precursors containing the N-CH₂-arene group. The benzimidazolium halides were readily converted into ruthenium(II)-NHC complexes with the general formula [RuCl₂(η⁶,η¹-arene-CH₂-NHC)]. The structures of all new compounds were characterized by ¹H NMR (Nuclear Magnetic Resonance), 13 C NMR, FT-IR (Fourier Transform Infrared) spectroscopy and elemental analysis techniques. The single crystal structure of one benzimidazole ruthenium complex, 2b , was determined. The complex is best thought of as containing an octahedrally coordinated Ru center with the arene residue occupying three sites, the remaining sites being occupied by a (carbene)C-Ru bond and two Ru-Cl bonds. The catalytic activity of [RuCl₂(η⁶,η ¹ -arene-CH₂-NHC)] complexes was evaluated in the direct (hetero)arylation of 2-phenylpyridine with (hetero)aryl chlorides in water as the nontoxic reaction medium. These results show that catalysts 2a and 2b were the best for monoarylation with simple phenyl and tolyl chlorides. For functional aryl chlorides, 2d , 2e , and 2c appeared to be the most efficient., Competing Interests: The authors declare that they have no conflict of interest.

Herein, we report that under mild solvolytic conditions, enantioenriched bromochlorides can be ionized, stereospecifically cyclized to an array of complex bromocyclic scaffolds, or intermolecularly trapped by exogenous nucleophiles. Mechanistic investigations support an ionic mechanism wherein the bromochloride serves as an enantioenriched bromonium surrogate. Several natural product-relevant motifs are accessed in enantioenriched form for the first time with high levels of stereocontrol, and this technology is applied to the scalable synthesis of a polycyclic brominated natural product. Arrays of nucleophiles including olefins, alkynes, heterocycles, and epoxides are competent traps in the bromonium-induced cyclizations, leading to the formation of enantioenriched mono-, bi-, and tricyclic products. This strategy is further amenable to intermolecular coupling between cinnamyl bromochlorides and a diverse set of commercially available nucleophiles. Collectively, this work demonstrates that enantioenriched bromonium chlorides are configurationally stable under solvolytic conditions in the presence of a variety of functional groups.

A novel and practical chiral ruthenium-NHC-diamine system is disclosed for the enantioselective hydrogenation of isocoumarins, which provides a new concept to apply (chiral) NHC ligands in asymmetric catalysis. A variety of optically active 3-substituted 3,4-dihydroisocoumarins were obtained in excellent enantioselectivities (up to 99% ee). Moreover, this methodology was utilized in the synthesis of O-methylmellein, mellein, and ochratoxin A.

Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH⁺ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH⁺ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX) increased the ALDH⁺ subpopulation.

The microwave-assisted three-component reactions of 3,5-bis(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones, acenaphthenequinone and cyclic α-amino acids in an ionic liquid, 1-butyl-3-methylimidazolium bromide, occurred through a domino sequence affording structurally intriguing diazaheptacyclic cage-like compounds in excellent yields.

3D frameworks are important because of their potential to combine the advantageous properties of porous materials with those associated with polymers. A series of novel 3D aromatic frameworks are presented that incorporate the heterocycles thiophene, selenophene, and tellurophene. The specific surface area and pore width of frameworks depends on the element that is used to build the framework. Optoelectronic properties are element-dependent, with heavy atoms red-shifting the optical properties and decreasing the energy gap of the solid. The metalloid nature of tellurophene allows the properties of this material to be tuned based on its oxidation state, even as an insoluble solid. The incorporation of the optoelectronic active thiophene, selenophene, and tellurophene units and the effect that they have on properties was studied. A supercapcitor device was fabricated using these frameworks, showing that these 3D frameworks are promising for optoelectronic uses., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

An efficient zinc(II)-catalyzed alkyne oxidation/C-H functionalization sequence was developed, thus leading to highly site-selective synthesis of a variety of isoquinolones and β-carbolines. Importantly, in contrast to the well-established gold-catalyzed intermolecular alkyne oxidation, over-oxidation can be completely suppressed in this system and the reaction most likely proceeds by a Friedel-Crafts-type pathway. Mechanistic studies and theoretical calculations are described., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel asymmetric organocatalytic 1,6-addition/1,4-addition sequence to 2,4-dienals is described. Based on a 1,6-Friedel-Crafts/1,4-oxa-Michael cascade, the organocatalyst directs the reaction of hydroxyarenes with a vinylogous iminium-ion intermediate to give only one out of four possible regioisomers, thus providing optically active chromans in high yields and 94-99 % ee. Furthermore, several transformations are presented, including the formation of an optically active macrocyclic lactam. Finally, the mechanism for the novel reaction is discussed based on computational studies., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A comparative study using NMR spectroscopy and designed top-pan molecular balances demonstrates that the noncovalent interaction of a hydroxy group with π-deficient pyrazine and quinoxaline units involves a lone pair-heteroarene interaction which is much stronger and solvent independent when measured relative to the classical π-facial hydrogen bond to a benzene ring. Alkyl fluorides also prefer the heteroarene rings over the benzene ring. The attractive interaction between a quinoxaline and a terminal alkyne is also stronger than the intramolecular hydrogen bond to an arene., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Given the important agricultural and medicinal application of optically pure heterocycles bearing a trifluoromethyl group at the stereogenic carbon center in the heterocyclic framework, the exploration of efficient and practical synthetic strategies to such types of molecules remains highly desirable. Catalytic enantioselective synthesis has one clear advantage that it is more cost-effective than other synthetic methods, but remains limited by challenges in achieving excellent yield and stereoselectivities with a low catalyst loading. Thus far, numerous models of organo- and organometal-catalyzed asymmetric reactions have been exploited to achieve this elusive goal over the past decade. This review article describes recent progress on this research topic, and focuses on an understanding of the catalytic asymmetric protocols exemplified in the catalytic enantioselective synthesis of a wide range of complex enantioenriched trifluoromethylated heterocycles., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The new histone deacylases inhibitors (HDACi) were synthesized in the class of 5-membered cyclic hydroxamic acids (5-CHA), showing medium size CHA as a new Zn-binding group. New reaction sequence was proposed for the synthesis of 5-membered alkylidene-cyclic-hydroxamic acids starting from butyrolactone. Compound 10c showed low µM activity on HeLa cell extracts. From these results, cyclic hydroxamic acids will be further investigated to find more potent compounds.

1,2,3-Triazole has become one of the most important heterocycles in contemporary medicinal chemistry. The development of the copper-catalyzed Huisgen cycloaddition has allowed the efficient synthesis of 1-substituted 1,2,3-triazoles. However, only a few methods are available for the selective preparation of 2-substituted 1,2,3-triazole isomers. In this context, we decided to develop an efficient flow synthesis for the preparation of various 2-aryl-1,2,3-triazoles. Our strategy involves a three-step synthesis under continuous-flow conditions that starts from the diazotization of anilines and subsequent reaction with malononitrile, followed by nucleophilic addition of amines, and finally employs a catalytic copper(II) cyclization. Potential safety hazards associated with the formation of reactive diazonium species have been addressed by inline quenching. The use of flow equipment allows reliable scale up processes with precise control of the reaction conditions. Synthesis of 2-substituted 1,2,3-triazoles has been achieved in good yields with excellent selectivities, thus providing a wide range of 1,2,3-triazoles., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

This work demonstrates how the directing ability of the azetidine ring could be useful for regioselective ortho-C-H functionalization of aryl compounds. Robust polar organometallic (lithiated) intermediates are involved in this synthetic strategy. The reagent n-hexyllithium emerged as a safer, yet still effective, basic reagent for the hydrogen/lithium permutation relative to the widely used reagent nBuLi. Two different reaction protocols were discovered for regioselective lithiation at the ortho positions adjacent to the azetidine ring, which served as a toolbox when other competing directing groups were installed on the aromatic ring. The coordinating ability of the azetidine nitrogen atom, as well as the involvement of dynamic phenomena related to the preferential conformations of 2-arylazetidine derivatives, were recognized to be responsible for the observed reactivity and regioselectivity. A site-selective functionalization of the aromatic ring was achieved for aryl azetidines with either coordinatively competent groups (e.g. methoxy) or inductively electron-withdrawing substituents (e.g. chlorine and fluorine). By fine-tuning the reaction conditions, regioselective introduction of several substituents on the aromatic ring could be realized. Several substitution patterns were accomplished, which included 1,2,3-trisubstitution, 1,2,3,4-tetrasubstitution, and 1,2,3,4,5-pentasubstitution, up to the exhaustive substitution of the aromatic ring., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Hypervalent-iodine-mediated oxidative coupling of the two aryl groups in either 2-acylamino-N-phenyl-benzamides or 2-hydroxy-N-phenylbenzamides, with concomitant insertion of the ortho-substituted N or O atom into the tether, has been described for the first time. This unusual metal-free rearrangement reaction involves an oxidative C(sp(2))-C(sp(2)) aryl-aryl bond formation, cleavage of a C(sp(2))-C(O) bond, and a lactamization/lactonization. Furthermore, unsymmetrical diaryl compounds can be easily obtained by removing the tether within the cyclized product., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The concise total syntheses of the bis(pyrroloindolines) (-)-lansai B and (+)-nocardioazines A and B are reported. The key pyrroloindoline building blocks are rapidly prepared by enantioselective formal [3+2] cycloaddition reactions. The macrocycle of (+)-nocardioazine A is constructed by an unusual intramolecular diketopiperazine formation., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A novel and regioselective umpolung synthesis of spirooxindoles has been developed by cooperative NHC-Lewis acid-mediated formal [3 + 2] annulations of alkynyl aldehydes with isatins. In most cases, the reactions proceeded via a(3)-d(3) umpolung of alkynyl aldehydes resulting in spirooxindole butenolides. In a few cases, spirooxindole furan-3(2H)-ones were formed as the major products via an a(1)-d(1) umpolung process by controlling the reaction temperature. These newly formed spirooxindoles could provide promising candidates for chemical biology and drug lead discovery.

A homologous set of 5,5-dimethylphlorin macrocycles in which the identity of one aryl ring is systematically varied has been prepared. These derivatives contain ancillary pentafluorophenyl (3H(Phl(F))), mesityl (3H(Phl(Mes))), 2,6-bismethoxyphenyl (3H(Phl(OMe))), 4-nitrophenyl (3H(Phl(NO2))), or 4-tert-butylcarboxyphenyl (3H(Phl(CO2tBu))) groups at the 15-meso-position. These porphyrinoids were prepared in good yields (35-50%) and display unusual multielectron redox and photochemical properties. Each phlorin can be oxidized up to three times at modest potentials and can be reduced twice. The electron-donating and electron-releasing properties of the ancillary aryl substituent attenuate the potentials of these redox events; phlorins containing electron-donating aryl groups are easier to oxidize and harder to reduce, while the opposite trend is observed for phlorins containing electron-withdrawing functionalities. Phlorin substitution also has a pronounced effect on the observed photophysics, as introduction of electron-releasing aryl groups on the periphery of the macrocycle is manifest in larger emission quantum yields and longer fluorescence lifetimes. Each phlorin displays an intriguing supramolecular chemistry and can bind 2 equiv of fluoride. This binding is allosteric in nature, and the strength of halide binding correlates with the ability of the phlorin to stabilize the buildup of charge. Moreover, fluoride binding to generate complexes of the form 3H(Phl(R))·2F(-) modulates the redox potentials of the parent phlorin. As such, titration of phlorin with a source of fluoride represents a facile method to tune the ability of this class of porphyrinoid to absorb light and engage in redox chemistry.

Among the currently available positron emitters suitable for Positron Emission Tomography (PET), (124)I has the longest physical half-life (4.2 days). The long half-life and well-investigated behavior of iodine in vivo makes (124)I very attractive for pharmacological studies. In this communication, we describe a simple yet effective method for the synthesis of novel (124)I labeled compounds intended for PET imaging of arylsulfatase activity in vivo. Arylsulfatases have important biological functions, and genetic deficiencies of such functions require pharmacological replacement, the efficacy of which must be properly and non-invasively evaluated. These enzymes, even though their natural substrates are mostly of aliphatic nature, hydrolyze phenolic sulfates to phenol and sulfuric acid. The availability of [(124)I]iodinated substrates is expected to provide a PET-based method for measuring their activity in vivo. The currently available methods of synthesis of iodinated arylsulfates usually require either introducing of a protected sulfate ester early in the synthesis or introduction of sulfate group at the end of synthesis in a separate step. The described method gives the desired product in one step from an aryl-alkyl cyclic sulfate. When treated with iodide, the source cyclic sulfate opens with substitution of iodide at the alkyl center and gives the desired arylsulfate monoester.

Perhydroindolic acids, the by-products obtained in the industrial production of a trandolapril intermediate, were used as chiral organocatalysts in asymmetric Michael addition reactions of aldehydes to nitroolefins. These proline-like catalysts are unique for their rigid bicyclic structure with two H atoms attached to the bridgehead C atoms lying on the opposite side of the ring. They therefore showed high efficiency in asymmetric Michael additions of aldehydes to nitroolefins. Under the optimal conditions, excellent diastereo- and enantioselectivities (up to 99/1 dr and 98% ee) were obtained with high chemical yields for a series of aldehydes and nitroolefins using only 5 mol% catalyst loading. The methodology features easily available catalysts, high catalytic efficiency and environmentally green procedures., (This journal is © The Royal Society of Chemistry 2012)

Substituted hydroxymethylenebisphosphonic acid derivatives--either as dronic acids or their dronate sodium salts, are important pharmaceuticals in the treatment of diseases arising from excessive bone-resorption. Potential has also been identified in areas ranging from parasite-growth inhibition to immunological and cancer therapeutics. Representative clinically relevant N-heterocyclic derivatives include zoledronic and risedronic acids. The biochemical background and mechanism of action of these drugs are discussed, along with trends in structural development and future prospects. Synthetic routes to dronates are then summarized. The most popular route to valuable dronic acids involves the 3- component condensation of a substituted acetic acid, phosphorous acid, and phosphorus trichloride. However, the protocols recorded in the literature are very diverse. This review gives a critical account of reported methods, explores the contradictions and suggests a practical synthetic procedure after clarifying the inconsistencies described. Possible mechanisms of the reaction are also discussed.

A protocol for the Suzuki-Miyaura coupling of heteroaryl boronic acids and vinyl chlorides that minimizes protodeboronation is described. A combination of catalytic amounts of Pd(OAc)(2) and SPhos in conjunction with CsF in isopropanol effectively affords a variety of coupled products. Surprisingly, a dramatic temperature dependence in product selectivity was observed., (This journal is © The Royal Society of Chemistry 2012)

A series of Cu(II), Co(II), Pt(II) and Zn(II) coordination compounds has been prepared by the reaction of the metal chlorides with pyrazine-2-carboxylic acid, pyridine-2-carboxylic acid, imidazole-4-carboxylic acid, benzimidazole-2-carboxylic acid and 1-methylimidazole-2-carboxylic acid. The complexes were characterized by IR, UV-VIS, elemental analysis, and some by (1) H-NMR, X-ray crystallography, HPLC and LC/MS spectroscopy. All complexes consist of a 2:1 ratio of ligand to metal ion. IR and X-ray crystallography show that coordination is through the nitrogen and carboxylate oxygen donor atoms of the ligand to form chelating rings. DFT calculations predict that the trans-coordinated isomers are thermodynamically more stable than their cis-forms. Only one of five complexes studied by X-ray crystallography, Cu(II) complex of 1-methylimidazole-2-carboxylic acid showed a cis-configured metal ion center. HPLC analysis indicated that Pt(II) complex of 1-methylimidazole-2-carboxylic acid is dominated (>90%) by the trans-configured complex. All other complexes showed one isomer, presumably the trans-form. The cytotoxic activity was investigated in human cancer cell lines in vitro; only the Pt(II) complexes were active. The antimicrobial activity against four bacterial strains and one fungi was estimated by the MIC method and best results were found amongst the Co(II) complexes. These results indicate that trans-coordinated bischelating N,O-heterocyclic carboxylates of Pt(II) are an interesting new class of potential antitumor agents., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In the presence of a rhodium complex containing a newly developed chiral diene ligand, alkenes activated by a range of π-deficient or π-excessive heteroarenes engage in highly enantioselective conjugate additions with various arylboronic acids.

Radix Angelicae Sinensis, known as Danggui in China, is one of the most popular traditional Chinese medicines (TCMs), which is contained by more than 80 composite formulae. Modern researches indicate that phthalides, organic acids and their esters, polysaccharides are main chemical components related to the bioactivities and pharmacological properties of Danggui. Some of them, such as Z-ligustilide and ferulic acid, are selected as marker compounds to evaluate the quality of Danggui frequently. Because of the diversity of chemical structures and characters of these components, analytical methods of Danggui are various, including GC-MS, HPLC-DAD-MS, TLC, CE-DAD, and so on. Besides that, the development of analytical technology makes the quality control of Danggui more effective and reliable. Quality evaluation is from single or several components' analysis to fingerprinting, or in combination. Furthermore, bioactive components screening of Danggui has also attracted much attention, which will help us evaluate the selected marker components to some extent. In this paper, the literatures about the major phytoconstituents of Danggui, quality control and bioactive components screening methods have been reviewed. Main attention is given to the different methodologies developed to perform chemical analysis, including separation, detection and identification.

The first general synthesis of boron-substituted 1,2-dihydro-1,2-azaborines is described. The versatile 1,2-dihydro-1,2-azaborine precursor 4 is synthesized through a ring-closing metathesis-oxidation sequence. Treatment of 4 with a wide range of anionic nucleophiles furnishes the desired adducts 5 in good yields. The scope includes hydrogen- and a variety of carbon- and heteroatom-based nucleophiles. Furthermore, the boron-containing isostere (7) of the potent hypolipidemic agent, methyl 2-ethylphenoxyacetate (8), is readily prepared through our method.

A strategy for lead identification of new agonists of GPR109a, starting from known compounds shown to activate the receptor, is described. Early compound triage led to the formulation of a binding hypothesis and eventually to our focus on a series of pyrazole acid derivatives. Further elaboration of these compounds provided a series of 5,5-fused pyrazoles to be used as lead compounds for further optimization.

Purpose: Lipid bilayers regulate the passage of solutes into and between cellular compartments. A general prerequisite for this passage is the partitioning of the solute into the bilayer. We investigated the relationship between bilayer partitioning and permeation of three drug-like acids in liposomal systems consisting of phosphatidylcholine alone or mixed with cholesterol or charged lipids., Materials and Methods: Bilayer partitioning was determined by equilibrium dialysis. Bilayer permeation was studied with a luminescence assay which is based on the energy transfer of the permeant to intraliposomal terbium(III)., Results: The influence of the lipid composition on the pH-dependent membrane affinity was in accordance with the membrane rigidity and possible electrostatic interactions between the acids and the lipids. However, there was no direct relationship between membrane affinity and permeation. This seeming discrepancy was closer analyzed with numerical simulations of the permeation process based on the single rate constants for partitioning and translocation. The simulations were in line with our experimental findings., Conclusions: Depending on the single rate constants and on the geometry of the system, lipid bilayer permeation may positively, negatively or not correlate with the bilayer affinity of the permeant.

The 1H-pyrazole-3-carboxylic acid 2 was converted in good yield (69%) into the corresponding 1H-pyrazole-3-carboxamide 5 via reaction of the acid chloride 3 with 2,3- diaminopyridine (4). A different product, the 3H-imidazo[4,5-b] pyridine derivative 6, was formed from the reaction of 3 with 4 and base in benzene for 5 hours. The structures of the synthesized compounds were determined spectroscopically. The mechanism of the reaction between 3 and 4 was examined theoretically.

The reactions of the 2-benzoselenopyrylium (1A) and 2-benzotelluropyrylium cations (1B) with a variety of nucleophiles have been investigated. LiAlH(4), sodium alkoxide (NaOMe, NaOi-Pr and NaOt-Bu), diethylamine, n-butylamine and acetone reacted with 1 to give the 1H-isochromenes (2) and the corresponding 1-substituted products (4-9) under mild conditions in almost good to high yields. The 1-alkyl(phenyl)isoselenochromenes (10-13) and 1-benzylisochromenes (18A, 18B), which were produced by the reaction of the salts 1 with Grignard reagents, were converted to the corresponding 1,3-disubstituted 2-benzopyrylium salts (14-17, 19) by treatment with triphenylcarbenium tetrafluoroborate (Ph(3)C(+) BF(4)(-)), respectively. The 1-benzylselenopyrylium salts (19A) and 1-benzyltelluropyrylium salts (19B) exist in the solvent as an equilibrium mixture of the salts (19) and the corresponding (Z)-benzylidene compounds (20).

Conformational studies of potent and selective endothelin-A (ET(A)) receptor antagonists, 4-substituted (R)-2-(benzo[1,3]-dioxol-5-yl)-6-isopropoxy-2H-chromene-3-carboxylic acids, are reported. X-ray crystallography and NMR studies of the 4-anisyl derivative 2 (S-1255), the stable atropisomers 3 and the 4-n-butyl derivative 4 reveal that the A-, B- and C-rings in these compounds adopt a L-like conformation in both solution and solid states. Molecular mechanics calculation shows that this L-like conformation is an inevitable conformation as determined by intramolecular steric repulsions. These 2H-chromene derivatives bound to an ET(A) receptor with IC(50) values of less than 1 nM, whereas the dihydro compounds 7 and 9 not having the L-like conformation showed weaker affinities. These results suggest that the L-like conformation is specifically recognized by the active site of the ET(A) receptor. The roles of the L-like conformation in the receptor binding are discussed.

Cationic Lewis acid complexes [Sc(pyridyl-bis(oxazolinyl)](Cl(2))SbF(6) 1a and 1b catalyze aldol reactions with ethyl glyoxylate with enantioselectivities ranging from 90 to 99% ee and syn reaction diastereoselections ranging from 90:10 to 95:5. [reaction: see text]

[structure: see text] Bisbinaphthyl-based macrocycles are found to carry out highly enantioselective fluorescent recognition of alpha-hydroxycarboxylic acids. It is observed that within a certain concentration range, one enantiomer of the chiral acids can increase the fluorescence intensity of the macrocycles by 2-3-fold, while the other enantiomer scarcely enhances the fluorescence. Such unusually high enantioselective responses make these macrocycles very attractive as fluorescent sensors in determining the enantiomeric composition of alpha-hydroxycarboxylic acids.