Ortho Hydroxyl Research Articles

Isolation of flavonoids from onion skins and their effects on K562 cell viability

<p class="Abstract">To investigate the anti-proliferative activity of flavonoids from onion skins, extraction by 50% ethanol (v/v), soxhlet polar fractionation, pH gradient separation, thin-layer chromatography, and recrystallization methods were used to isolate and purify flavonoids from dry onion skins. Anti-proliferative activities of some flavonoids obtained on leukemia K562 cell line were deter-mined by MTT assay. Results showed that flavonoids of onion skins were mainly in form of quercetin, kaempferol, isorhamnetin, apigenin-7-O-β-D-glucopyranoside, quercetin-3-O-β-D-glucopyranoside, kaempferol-7-O-β-D-glucopyranoside and rutin. Quercetin and kaempferol decreased K562 cell viability, and quercetin had stronger effect. However, isorhamnetin and rutin exhibited certain proliferation-promoting effects. It suggests that ortho hydroxyl groups on B ring of onion flavonoids might be the key structural elements of their cytotoxic effects on K562 cells, and hydroxyl groups in position 3 or carbonyl groups in position 4 might be one of the structural effect elements.</p><p> </p>

Excited-State Proton-Transfer-Induced Trapping Enhances the Fluorescence Emission of a Locked GFP Chromophore.

The chemical locking of the central single bond in core chromophores of green fluorescent proteins (GFPs) influences their excited-state behavior in a distinct manner. Experimentally, it significantly enhances the fluorescence quantum yield of GFP chromophores with an ortho-hydroxyl group, while it has almost no effect on the photophysics of GFP chromophores with a para-hydroxyl group. To unravel the underlying physical reasons for this different behavior, we report static electronic structure calculations and nonadiabatic dynamics simulations on excited-state intramolecular proton transfer, cis–trans isomerization, and excited-state deactivation in a locked ortho-substituted GFP model chromophore (o-LHBI). On the basis of our previous and present results, we find that the S1 keto species is responsible for the fluorescence emission of the unlocked o-HBI and the locked o-LHBI species. Chemical locking does not change the parts of the S1 and S0 potential energy surfaces relevant to enol–keto tautomerization; hence, in both chromophores, there is an ultrafast excited-state intramolecular proton transfer that takes only 35 fs on average. However, the locking effectively hinders the S1 keto species from approaching the keto S1/S0 conical intersections so that most of trajectories are trapped in the S1 keto region for the entire 2 ps simulation time. Therefore, the fluorescence quantum yield of o-LHBI is enhanced compared with that of unlocked o-HBI, in which the S1 excited-state decay is efficient and ultrafast. In the case of the para-substituted GFP model chromophores p-HBI and p-LHBI, chemical locking hardly affects their efficient excited-state deactivation via cis–trans isomerization; thus, the fluorescence quantum yields in these chromophores remain very low. The insights gained from the present work may help to guide the design of new GFP chromophores with improved fluorescence emission and brightness.

Synthesis of novel benzohydrazone–oxadiazole hybrids as β-glucuronidase inhibitors and molecular modeling studies

A series of compounds consisting of 25 novel oxadiazole–benzohydrazone hybrids (6–30) were synthesized through a five-step reaction sequence and evaluated for their β-glucuronidase inhibitory potential. The IC50 values of compounds 6–30 were found to be in the range of 7.14–44.16μM. Compounds 6, 7, 8, 9, 11, 13, 18, and 25 were found to be more potent than d-saccharic acid 1,4-lactone (48.4±1.25μM). These compounds were further subjected for molecular docking studies to confirm the binding mode towards human β-d-glucuronidase active site. Docking study for compound 13 (IC50=7.14±0.30μM) revealed that it adopts a binding mode that fits within the entire pocket of the binding site of β-d-glucuronidase. Compound 13 has the maximum number of hydrogens bonded to the residues of the active site as compared to the other compounds, that is, the ortho-hydroxyl group forms hydrogen bond with carboxyl side chain of Asp207 (2.1Å) and with hydroxyl group of Tyr508 (2.6Å). The other hydroxyl group forms hydrogen bond with His385 side chain (2.8Å), side chain carboxyl oxygen of Glu540 (2.2Å) and Asn450 side-chain’s carboxamide NH (2.1Å).

Anthocyanin-rich extracts from blackberry, wild blueberry, strawberry, and chokeberry: antioxidant activity and inhibitory effect on oleic acid-induced hepatic steatosis in vitro.

Limited information is available regarding the relationship between the chemical structures and inhibitory effects of anthocyanin (ACN) on triglyceride (TG) overaccumulation. Thus this study investigated the antioxidant activity and inhibitory effect of blackberry, wild blueberry, strawberry, and chokeberry ACN-rich extracts, with different structural characteristics, on oleic acid-induced hepatic steatosis in vitro. Four major ACNs from these berries, with different aglycones, namely cyanidin-3-glucoside (Cy-3-glu), delphinidin-3-glucoside, pelargonidin-3-glucoside, and malvidin-3-glucoside, were also investigated. Blackberry ACN-rich extract exhibited the most significant inhibitory effect on TG clearance (30.5% ± 3.4%) and reactive oxygen species generation. TG clearance was significantly correlated with total phenolic content (r = 0.991, P < 0.05) and oxygen radical absorbance capacity value (r = 0.961, P < 0.05). Furthermore, Cy-3-glu showed the highest inhibitory effect on intracellular TG overaccumulation, with a maximum TG clearance of 61.3% at 40 µg mL(-1) . Our findings suggest that the inhibitory effects of different ACNs on oleic acid-induced hepatic steatosis significantly vary. Cy-3-glu, which contains the ortho hydroxyl group in its B ring, possibly confers the protective effects of antioxidants and inhibits TG accumulation in HepG2 cells. © 2015 Society of Chemical Industry.

Synthetic and Structural Studies on Novel 4,3′-Bicoumarins

A series of directly linked 4-3′ bicoumarins have been synthesized by both Knoevenagel and Perkin reactions. This single-step transformation was accomplished by the reaction of coumarin-4-acetates with substituted salicylaldehydes in presence of piperidine using ethanol as solvent and by the reaction of coumarin-4-acetic acids with substituted salicylaldehydes in the presence of sodium hydride in acetic anhydride. Greater yields have been obtained in the sodium hydride and acetic anhydride condition. An intermediate chalcone with an ortho-hydroxyl group, which is a precursor for lactone formation, has been isolated and its structure has been confirmed by x-ray analysis. The nonplanar S-cis arrangement of two C4-C3’ double bonds has been confirmed by nuclear Overhauser spectroscopy (NOE) and x-ray studies. The UV-fluorescence studies support the formation of a conjugated bicoumarin system.

New heterocyclic metallomesogens: synthesis, mesomorphic and thermal behaviours of Cu(II) complexes with 1,2,3-triazole-based Schiff bases ligands

Two series of new Cu(II) complexes derived from the reaction of copper acetate with the non-linear 1,2,3-triazole-based Schiff bases have successfully been synthesised. The structures of the ligands and its complexes were elucidated by elemental analysis, FT-IR, 1H-NMR and UV–visible spectroscopic techniques. The differential scanning calorimetry and polarizing optical microscopy supported the anisotropic properties of uncoordinated ligands in which the focal conic fan-shaped texture and/or broken fan-shaped texture characteristics of respective SmA and SmC phases were recorded. However, not all of their corresponding Cu(II) complexes are mesogenic. Although the iodo-substituted ligands with even parity C10H29 to C14H33 are non-stable and exhibit SmA phase which is not reproducible, the ultimate Cu(II) complexes show exclusively stable SmA phase. This observation can be ascribed to the enhanced colinearity and molecular anisotropic by the presence of Cu-N and Cu-O coordination modes. On the other hand, the comparison studies show that different positions of ortho-hydroxyl group affect the mesomorphic and thermal behaviour of ligands and Cu(II) complexes.

Mechanism of reactive carbonyl species trapping by hydroxytyrosol under simulated physiological conditions

This investigation reveals that hydroxytyrosol (HT) could compete with lysine, arginine and histidine to bind methylglyoxal (MGO) and reducing the formation of advanced glycation end products. Kinetic of the degradation of HT in presence/absence of MGO under simulated physiological conditions is monitored by HPLC coupled to a QTOF spectrometer. HT should previously be oxidized to DOPAC (3,4-dihydroxyphenylacetic acid) which reacts with MGO by electrophilic aromatic substitution of the ortho-diphenyl ring. DOPAC was detected as the major degradation product of HT under simulated physiological conditions. Ortho-hydroxyl groups are necessary to promote the nucleophilic addition of MGO by HT and related compounds. The formation of four adducts were described by mass spectrometry, but monoDOPAC-monoMGO adduct (C11H12O6) was predominant. Results suggest that HT and its degradation product DOPAC could have a relevant role in preventing the formation of advanced glycation end products and therefore potentially mitigate the diabetic complications.

Locked ortho- and para-core chromophores of green fluorescent protein; dramatic emission enhancement via structural constraint.

We report the design strategy and synthesis of a structurally locked GFP core chromophore p-LHBDI, its ortho-derivative, o-LHBDI, and H2BDI possessing both para- and ortho-hydroxyl groups such that the inherent rotational motion of the titled compounds has been partially restricted. o-LHBDI possesses a doubly locked configuration, i.e., the seven-membered ring hydrogen bond and five-membered ring C(4-5-10-13-14) cyclization, from which the excited-state intramolecular proton transfer takes place, rendering a record high tautomer emission yield (0.18 in toluene) and the generation of amplified spontaneous emission. Compared with their unlocked counterparts, a substantial increase in the emission yield is also observed for p-LHBDI and H2BDI in anionic forms in water, and accordingly the structure versus luminescence relationship is fully discussed based on their chemistry and spectroscopy aspect. In solid, o-LHBDI exhibits an H-aggregate-like molecular packing, offers narrow-bandwidth emission, and has been successfully applied to fabricate a yellow organic light emitting diodes (λmax = 568 nm, ηext = 1.9%) with an emission full width at half-maximum as narrow as 70 nm.

The protective effects of berry-derived anthocyanins against visible light-induced damage in human retinal pigment epithelial cells.

Studies have shown that anthocyanins (ACNs) in berries contribute to eye health. However, information on the relationship between the chemical structures and visual functions of ACNs is scarce. This study investigated the protection effects of ACNs with different structures against visible light-induced damage in human retinal pigment epithelial (RPE) cells. Four ACNs with different aglycones, namely, pelargonidin-3-glucoside (Pg-3-glu), cyanidin-3-glucoside (Cy-3-glu), delphinidin-3-glucoside, and malvidin-3-glucoside (Mv-3-glu), were isolated from three berries (blueberry, blackberry and strawberry). Of these ACNs, Cy-3-glu exhibited the highest reactive oxygen species inhibitory capacity in RPE cells, with 40 µg mL(-1) Cy-3-glu showing a ROS clearance of 57.5% ± 4.2%. The expression of vascular endothelial growth factor levels were significantly (P < 0.05) down-regulated by Cy-3-glu and Mv-3-glu in a visible light-induced damage RPE cell model. Cy-3-glu and Pg-3-glu treatments significantly (P < 0.05) inhibited the increase in β-galactosidase during the RPE cell ageing caused by visible light exposure. Our findings suggest that the biological properties of different ACNs significantly vary. Cy-3-glu, which contains an ortho hydroxyl group in its B ring, possibly exerts multiple protective effects (antioxidant, anti-angiogenic and anti-ageing) in RPE cells. Therefore, Cy-3-glu may prove useful as a prophylactic health food for the prevention of retinal diseases.

Modification, biological evaluation and 3D QSAR studies of novel 2-(1,3-diaryl- 4,5-dihydro-1H-pyrazol-5-yl)phenol derivatives as inhibitors of B-Raf kinase.

A series of novel 2-(1,3-diaryl- 4,5-dihydro-1H-pyrazol-5-yl)phenol derivatives (C1–C24) have been synthesized. The B-Raf inhibitory activity and anti-proliferation activity of these compounds have been tested. Compound C6 displayed the most potent biological activity against B-RafV600E (IC50 = 0.15 µM) and WM266.4 human melanoma cell line (GI50 = 1.75 µM), being comparable with the positive control (Vemurafenib and Erlotinib) and more potent than our previous best compounds. The docking simulation was performed to analyze the probable binding models and poses while the QSAR model was built to check the previous work as well as to introduce new directions. This work aimed at seeking more potent inhibitors as well as discussing some previous findings. As a result, the introduction of ortho-hydroxyl group on 4,5-dihydro-1H-pyrazole skeleton did reinforce the anti-tumor activity while enlarging the group on N-1 of pyrazoline was also helpful.

Crystallization-enhanced emission through hydrogen-bond interactions in blends containing hydroxyl-functionalized azine and poly(4-vinyl pyridine)

An organic azine derivative of CN4OH, containing both para- and ortho-hydroxyl (o- and p-OH) groups, is a fluorescent material with an emission efficiency dependent on the degree of crystallinity.

2-Hydroxy-substituted cinnamic acids and acetanilides are selective growth inhibitors of Mycobacterium tuberculosis

Selective chemical hits are required for feeding the initial discovery phase of the anti-tuberculosis therapeutics pipeline. These chemical entities should ideally target novel mechanisms of action in order to tackle drug resistance in Mycobacterium tuberculosis. In this work, hydroxycinnamic acid and acetamidophenol skeleta were employed for assessing the effects of constitutional isomerism on in vitro anti-TB activity. The whole cell evaluation of minimum inhibitory concentration values of different substituted cinnamic acids and acetamidophenols showed that the free ortho hydroxyl group conferred both potency and selectivity. Both 2-coumaric acid and 2-acetamidophenol showed minimum inhibitory concentration below 150 μM against M. tuberculosis H37Rv and selectivity index higher than 30.

A-Type Proanthocyanidins Prevent Engraftment Of Primary Acute Myelogenous Leukemia Cells In Mice and Exhibit Potentially Novel Anti-Leukemia Mechanisms

Acute myelogenous leukemia (AML) is often a fatal disease where after strong induction therapy most patients relapse and die. AML originates and is maintained by leukemia stem cells (LSCs). Failure to eliminate LSCs by chemotherapy is likely to result in disease relapse. Therefore, it is a priority to identify new therapies that eliminate blasts while ablating LSCs and preventing a relapse.We have found that a unique class of compounds in cranberries (Vaccinium macrocarponAit.), known as A-type proanthocyanidins (A-PACs), were effective against several leukemia cell lines and primary AML samples in vitro. A-PACs consist of monomeric epicatechin units attached to one another by a carbon-carbon bond and a distinctive ether bond that differentiates these compounds from other proanthocyanidins found in nature. Moreover, A-PACs possess ortho-hydroxyl phenolic groups that have the potential to bind to iron and alter redox status.Preliminary work showed that pre-treatment with antioxidants or holo-transferrin (iron-saturated transferrin) partially protected AML cells from A-PAC induced cell death (p<0.01). A-PACs were also found to selectively ablate leukemia stem and progenitor cells, with minimal effects on normal hematopoetic stem cells. Furthermore, AML engraftment of cells treated ex vivo with 62.5 µg/ml A-PACs was decreased (90.6%, n=3, p<0.001), while normal CD34+ cells retained engraftment capability in immunodeficient mice. It was also found that a fraction of A-PACs of up to 7 degree of polymerization was more effective than individual A-PACs. This information prompted us to investigate the in vivo anti-leukemia effects of A-PACs in xenotransplanted mice with primary AML samples, and to further investigate the mechanisms associated with these compounds.Primary AML cells were injected in sub-lethally irradiated NOD/SCID mice. Four weeks after injections, when human leukemia cells have engrafted, intraperitoneal injections of cytarabine (AraC) at 60 mg/kg were given to the mice for 1 week everyday or A-PACs (100 mg/kg dose every 3 days for A-PACs) and vehicle control (1% DMSO in PBS every 3 days) were injected for 2.5 weeks. Mice were sacrificed and leukemia engraftment evaluated using anti-human CD45 and CD33. Moreover, primary cells treated with A-PACs were assessed for effects on iron metabolism, ROS, and survival pathways either by gene expression analysis, flow cytometry or mass spectrometry.Administration of A-PACs to NOD-SCID mice bearing AML tumors reduced tumor burden. Mice that were treated with the vehicle control had engraftment of AML primary cells equivalent to 16.1% (95% CI: -6.0, 38.37; n=4), whereas the mice treated with the A-PACs and AraC showed a level of engraftment of 4.9% (95% CI: 2, 8; n=5) and 5.8% (95% CI: -1.1, 12.7; n=5), respectively. No significant changes in hemoglobin or weight were found between the different treatment groups. Moreover, qPCR analysis of sensitive leukemia cell lines treated with A-PACs showed changes in gene expression of several iron metabolism genes in sensitive leukemia cell lines (up-regulation of ferritin and transferrin receptors 1 and down-regulation of ferroportin) and several ROS-relevant genes (down-regulation of nuclear factor erythroid-2-related factor 2 and glutamate-cysteine ligase regulatory subunit). Mass spectrometry also confirmed that A-PACs bind iron.The results indicate that A-PACs not only target primary AML cells in vitro but are also effective in vivo. Secondary transplants are also being performed to determine the effects on LSC activity. Some of the anti-leukemia mechanisms under investigation include effects related to iron metabolism, ROS or inhibition of survival pathways. Understanding the unique structure and biological effects of A-PACs may provide novel information about pathways involved in the survival of LSCs and provide crucial information in preparation for clinical trials and/or optimal combination drug therapies. Disclosures:Rivella:Novartis: Consultancy; Bayer: Consultancy; Isis: Consultancy, Research Funding; Merganser: Equity Ownership, Research Funding; Biomarin: Consultancy; Alexion: Consultancy; Imago: Consultancy.

Depletion of high-abundance flavonoids by metal complexation and identification of low-abundance flavonoids in Scutellaria baicalensis Georgi

The complexation of metal cations and flavonoids with 5-hydroxyl or ortho-hydroxyl groups was successfully used for high-abundance flavone depletion from a botanical extract in this study. Due to their structural differences, five of the most highly abundant constituents, baicalin, wogonoside, baicalein, wogonin and oroxylin A, were successfully depleted from the ethanol extract of Radix Scutellariae. The depletion rates were approximately 99%, 85%, 99%, 70% and 76%, respectively. The recoveries of low-abundance constituents were very strong (approximately 70–100%). The efficiency of the low-abundance compounds’ identification by high performance liquid chromatography electrospray tandem mass spectrometry (HPLC ESI MS/MS) was remarkable after the high-abundance constituents were removed. The number of compounds identified from the HPLC MS/MS data was 250% greater than the number of compounds identified in the untreated total extract. One hundred seventeen flavonoids were identified in the ethanol extract of Radix Scutellariae using this method, which was much greater than the number identified in previous studies without high-abundance constituent depletion. Among them, 13 sulphated flavonoids were identified. These low-abundance sulphated flavonoids can barely be detected in untreated total extracts. To the best of our knowledge, this is the first reported evidence that sulphated flavonoids have been identified from Radix Scutellariae. This method will facilitate the removal of high-abundance flavonoids and the identification of low-abundance compounds in botanical extracts.

Novel kinetic method for expressing the ability of antioxidant to scavenge radicals

A method was developed to treat the result from an antioxidant trapping radicals including 2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonate) cationic radical(ABTS+·), 2,2′-diphenyl-1-picrylhydrazyl radical(DPPH), and galvinoxyl radical. In the presence of a certain concentration of an antioxidant, the decrease of the concentration of a kind of radicals follows the second order exponential function with the increase of the reaction time(t), viz., [radical]=Ae−t/a+Be−t/b+C, the derivation operation of which obtains the differential style, −d[radical]/dt= (A/a)e−t/a+(B/b)e−t/b, revealing the relationship between the reaction rate(r=-d[radical]/dt) and the reaction time(t). Thus, the reaction rate at the beginning of the reaction(r0) can be calculated by assigning t=0 in the equation of -d[radical]/dt-t. Based on the concept of the reaction rate, r=k[radical][antioxidant], the rate constant(k) can be calculated based on r0 and the initial concentrations of radical and antioxidant, k=r0/([radical]0[antioxidant]0). The k means the rate of a fresh antioxidant molecule to trap a fresh radical. This method was used to treat the interactions of ABTS+·, DPPH, and galvinoxyl radicals with three homoisoflavonoids, four pyrazoles, and three ferrocenyl Schiff bases. It was found that ferrocenyl group is beneficial for antioxidants to reduce ABTS+·, and ortho-hydroxyl group is beneficial for antioxidants to donate hydrogen atom in phenolic hydroxyl group to DPPH and galvinoxyl radicals.

New two-photon absorption organic chromophores containing imino and hydroxyl groups: synthesis, ESIPT and chemosensors

In this work, a variety of new conjugated chromophores containing imino and hydroxyl groups are presented. Excited state intramolecular proton transfer (ESIPT) of these chromophores under one- and two-photon irradiation was surveyed. One-photon absorption spectra show the presence of internal hydrogen bond in the organic dyes containing ortho-hydroxyl group, while the corresponding dyes carrying para-hydroxyl group do not exhibit intramolecular H-bonding effect. In the most of aprotic and protic solvents, the extended chromophores bearing ortho-hydroxyl group exhibit well-separated dual emission bands with large Stokes shift (ca. 160 nm), as contrast, the molecules containing para-hydroxyl group exhibit only single band with normal Stokes shift (ca. 50 nm). Two-photon absorption (TPA) induced competitive ESIPT emission can also be observed by near-infrared (near-IR) femtosecond laser to the molecules carrying ortho-hydroxyl group. The experiments show that the molecules carrying ortho-hydroxyl group are able to undergo ESIPT under one- and two-photon excitation, while the molecules containing para-hydroxyl groups do not exhibit such properties. 2-((3′,4′-Dimethoxyl-phenylethyleneyl-phenyl-4-ylimino)methyl)phenol (C1) and 2-((3′,4′,5′- trimethoxyl-phenylethyleneyl-phenyl-4-ylimino)methyl)phenol (C3) exhibit regular and selective response to Zn2+ in DMF. The molecular modeling was further performed to analyze ESIPT occurrence theoretically.

Radical-scavenging and rat liver mitochondria lipid peroxidative inhibitory effects of natural flavonoids from traditional medicinal herbs

Baicalein (a), baicalin (b), daidzein (c), myricetin (d), oroxylin A (e), quercetin (f), quercetin pentaacetate (g), quercitrin (h), and wogonin (i) were isolated from regular anti-inflammatory Chinese herbs which contain many flavonoids compounds, also the radical-scavenging and liver mitochondrial lipid peroxidation (LPO) inhibitory capabilities were elucidated. The 50% inhibitory concentrations (IC50) for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capability of (a), (b), (d), (f), and (g) were 3.61, 3.28, 2.41, 2.16, and 3.74 μg/ml, and for LPO inhibition were 9.32, 9.52, 19.63, 16.15, and 20.22 μg/ml, respectively. The antioxidant capacities of (d), (f), (g), (h), (b), and (a) were 20.46, 16.42, 14.46, 13.98, 12.74, and 8.13 μMTrolox equivalents, respectively. To compare with the structure-activity relationships of the flavonoids, two flavones of baicalein and baicalin which have 5,6-hydroxy group which contain ortho-hydroxyl group characteristic reveal better LPO inhibitory activity, and two flavonols of myricetin, quercetin which have 5,7-trihydroxy group have more DPPH activity and ferrous chelating ability. The hydroxyl groups might play a role in increasing the activity of the flavonoids and exhibit potent antioxidant activities. In view of these results, five of the nine natural flavonoids (baicalein, baicalin, myricetin, quercetin and quercetin pentaacetate) can be lead compounds for preventing liver damage and related iron-overload disease. Key words: Anti-inflammatory Chinese herbs, ferrous ion, flavonoids, lipid peroxidation.

Observation of neighboring ortho-hydroxyl group participation in organocatalytic asymmetric sequential Michael-lactonization reactions: synthesis of highly substituted chiral spirodihydrocoumarins

A general approach to asymmetric synthesis of highly substituted spirodihydrocoumarins with a quaternary stereocenter was achieved through neighboring ortho-hydroxyl group induced sequential Michael-lactonization reactions on 2-(2-nitrovinyl)phenols with alkyl cyclopentanone-2-carboxylates in the presence of a catalytic amount of quinine-NH-thiourea followed by p-TSA.

A practicable environmentally benign one-pot synthesis of 2-arylbenzofurans at room temperature

An environmentallyfriendly one-pot synthesis of 2-arylbenzofurans under ambient temperature has been developed. It features an ortho-hydroxyl group assisted Wittig reaction of substituted salicylaldehyde followed by an in situ oxidative cyclization. Its advantages include readily available and non-hazardous materials, benign reaction conditions (room temperature, green solvent and one-pot manner), easy work-up and high overall yields. Utilizing this methodology, various 2-aryl-benzofurans including four natural products have been synthesized.

Fluorescence turn-on probe for biothiols: intramolecular hydrogen bonding effect on the Michael reaction

Weakly fluorescent coumarinyl enones are rapidly transformed into strongly fluorescent molecules through the Michael addition reaction of a thiol group, where an intramolecular hydrogen bond plays a critical role in the reaction rate. The molecular probe ( 3) with an ortho hydroxyl group to a carbonyl group exhibits a rapid response toward GSH owing to the stabilization of the possible oxyanion intermediate by a preferable intramolecular hydrogen bond. Probe 1 with an o-hydroxyl group also showed a moderately enhanced reaction rate with GSH and soluble in HEPES buffer to exhibit a highly selective and sensitive fluorescence turn-on response toward biothiols.