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Chromone and flavone are both central backbones of natural products and clinical medicines. Synthesis of diversely functionalized chromones and flavones constitutes significant research contents of the modern synthetic science because abundant molecular libraries of such types are crucial in providing candidate compounds for the discovery of new pharmaceuticals and functional materials. The direct C H bond activation or functionalization on these heterocyclic backbones provides highly powerful tools for the rapid accesses to densely functionalized chromone and flavone derivatives. Considering the importance of the functionalized chromone and flavone compounds as well as the notable advances in the synthesis of such products by direct C H activation or functionalization, we review herein the research advances in the C H bond activation and functionalization reactions of chromone and flavones, in hope of showing the current states and promise of the research domain.

Four new flavone derivatives (1–4), together with six known flavones (5-10), were isolated from the stems of Dracaena angustifolia. The complete structures of new compounds were elucidated by analyses of spectroscopic data and quantum chemistry calculations. Compounds 2, 9 and 10 displayed weak anti-inflammatory activity with IC50 values of 45, 33 and 61 μM, respectively.

Tosyloxy- and mesyloxyflavones derived from abundant and biologically important hydroxyflavones were used to synthesize a series of functionalized flavones through versatile palladium-catalyzed cross-coupling reactions. A Pd(OAc)2/2-[2-(dicyclohexylphosphino)phenyl]-1-methyl-1H-indole system effectively catalyzed the reactions of a broad range of tosyloxy- and mesyloxyflavones as electrophilic coupling partners with various nucleophiles to give the corresponding products in good to excellent yields. Catalyst loadings of as little as 0.1 mol% Pd were successfully used. Importantly, we demonstrated that this protocol provided a significantly improved efficiency in the synthesis of a potential chromen-4-one-based analogue of a potent inhibitor of DNA-dependent protein kinase.

Funder: Gatsby Charitable Foundation; doi: http://dx.doi.org/10.13039/501100000324, Funder: Engineering and Physical Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000266, Funder: Biotechnology and Biological Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000268, Funder: AstraZeneca; doi: http://dx.doi.org/10.13039/100004325, Background: Dionysia tapetodes, a small cushion-forming mountainous evergreen in the Primulaceae, possesses a vast surface-covering of long silky fibres forming the characteristic “woolly” farina. This contrasts with some related Primula which instead form a fine powder. Farina is formed by specialized cellular factories, a type of glandular trichome, but the precise composition of the fibres and how it exits the cell is poorly understood. Here, using a combination of cell biology (electron and light microscopy) and analytical chemical techniques, we present the principal chemical components of the wool and its mechanism of exit from the glandular trichome. Results: We show the woolly farina consists of micron-diameter fibres formed from a mixture of flavone and substituted flavone derivatives. This contrasts with the powdery farina, consisting almost entirely of flavone. The woolly farina in D. tapetodes is extruded through specific sites at the surface of the trichome’s glandular head cell, characterised by a small complete gap in the plasma membrane, cell wall and cuticle and forming a tight seal between the fibre and hole. The data is consistent with formation and thread elongation occurring from within the cell. Conclusions: Our results suggest the composition of the D. tapetodes farina dictates its formation as wool rather than powder, consistent with a model of thread integrity relying on intermolecular H-bonding. Glandular trichomes produce multiple wool fibres by concentrating and maintaining their extrusion at specific sites at the cell cortex of the head cell. As the wool is extensive across the plant, there may be associated selection pressures attributed to living at high altitudes.

A number of 4'-substituted (R = H, Me, Cl, F) flavone derivatives is synthesized from 2-hydroxyacetophenones using the modified Baker–Venkataraman reaction. Compound [3-(4-fluorobenzoyl)-5- hydroxy-4'-fluoroflavone] was synthesized for the first time with the yield of 12%. Antiproliferative assays indicate that the synthesized flavones with F substituent at the 4' position demonstrate higher activity than the other flavone derivatives, particularly against HeLa and MCF-7 with the IC50 9.5 and 2.7 μM, respectively.

A series of flavones were synthesized from 2-hydroxyacetophenones using a modified Baker–Venkataraman reaction. The 2-hydroxyacetophenone, 2,4-dihydroxyacetophenone, or 2,5-dihydroxyacetophenone, or 2,6-dihydroxyacetophenone was treated with 2 equiv of a 4-substituted aroyl chloride in 99:1 (w/w) acetone/water using both K2CO3 (8 equiv) and pyridine (4 equiv) as bases. Various 4′-substituted (R=H, Me, Cl, F) flavone derivatives were obtained via this one-pot procedure in high yield (≥70%). This modified process is both simple and efficient. Compound 26b (3-(4-fluorobenzoyl)-5-hydroxy-4′-fluoroflavone) was synthesized for the first time with a yield of 12%. The method was unsuccessful, however, for the synthesis of one flavone, 5-hydroxy-4′-methoxyflavone.

A series of novel flavone derivatives were designed, synthesized, and evaluated for their H3 R inhibitory activity. The results showed that four compounds exhibited significant anti-H3 R activity. Molecular docking experiments indicated that a salt bridge, hydrogen-bonding, and hydrophobic interactions all contributed to interactions between inhibitors and H3 R.

Flavonoids are widely occurring polyphenols of plant origin and well explored in the field of pharmacological activities. Recent studies showed this scaffold to be more dynamic as fluorescent probe. Very rare reports are there in literature on flavones as liquid crystals, for the first time we have synthesized and characterized flavone and bis-flavone derivatives for mesomorphic properties. Compounds 9a–d and 13a–d were studied for liquid crystalline properties by Differential scanning calorimetry (DSC) and Polarizing optical microscopy (POM) studies. The compounds 8, 9a–d, 12, and 13a–d were also studied for antioxidant property by DPPH assay. We have synthesized new n-alkoxy flavone and Bis-flavone derivatives for liquid crystalline properties. The compounds were characterized by using different spectral techniques, all synthesized compounds did not show mesophase which was confirmed by differential scanning calorimetry (DSC) and polarizing optical microscopy (POM) study. POM image of compound 9c in heating (a) shows direct melting (92.2°C) of compound and cooling (b) goes to crystallization (65.8°C) with no phase. Flavone derivatives are well reported to show broad pharmacological applications, we have also tested compounds for antioxidant properties by DPPH assay.

Neural stem cells (NSCs) differentiate into multiple cell types, including neurons, astrocytes, and oligodendrocytes, and provide an excellent platform to screen drugs against neurodegenerative diseases. Flavonoids exert a wide range of biological functions on several cell types and affect the fate of NSCs. In the present study, we investigated whether the structure-activity relationships of flavone derivatives influence NSC differentiation. As previously reported, we observed that PD98059 (2&prime, amino-3&prime, methoxy-flavone), compound 2 (3&prime, methoxy-flavone) induced astrocytogenesis. In the present study, we showed that compound 3 (2&prime, hydroxy-3&prime, methoxy-flavone), containing a 3&prime, methoxy group, and a non-bulky group at C2&prime, and C4&prime, induced astrocytogenesis through JAK-STAT3 signaling pathway. However, compound 1 and 7&ndash, 12 without the methoxy group did not show such effects. Interestingly, the compounds 4 (2&prime, 3&prime, dimethoxyflavone), 5 (2&prime, N-phenylacetamido-3&prime, methoxy-flavone), and 6 (3&prime, 4&prime, dimethoxyflavone) containing only 3&prime, methoxy could not promote astrocytic differentiation, suggesting that both the methoxy groups at C3&prime, and non-bulky group at C2&prime, are required for the induction of astrocytogenesis. Notably, compound 6 promoted neuronal differentiation, whereas its 4&prime, demethoxylated analog, compound 2, repressed neurogenesis, suggesting an essential role of the methoxy group at C4&prime, in neurogenesis. These findings revealed that subtle structural changes of flavone derivatives have pronounced effects on NSC differentiation and can guide to design and develop novel flavone chemicals targeting NSCs fate regulation.

Seventeen new flavone derivatives substituted at the 4&prime, OH position were designed, synthesized and evaluated for their anticancer and antibacterial activities. Among them, compounds 3, 4, 6f, 6e, 6b, 6c and 6k demonstrated the most potent antiproliferative activities against a human erythroleukemia cell line (HEL) and a prostate cancer cell line (PC3). The results also showed that the IC50 value of compounds 3, 4, 6f, 6e, 6b, 6c and 6k were close to that of the anticancer drug cisplatin (DDP) and lower than that of apigenin. All of the derivatives did not present antibacterial activities. The structure&ndash, activity relationships evaluation showed that the configuration of methyl amino acid might affect their biological activities.

A simple and efficient one pot method has been developed for the synthesis of some new functionalized pyrano fused flavone derivatives, alkyl 4,8-dioxo-2-phenyl-4,8-dihydropyrano[2,3-f]chromene-10-carboxylates and dialkyl 4-oxo-2-phenyl-4,8-dihydropyrano[2,3-f]chromene-8,9-dicarboxylates, from 7-hydroxy flavones and 7-hydroxy 8-formyl flavones using dialkylacetalynedicarboxylates in the presence of triphenyl phosphine. The structures of all synthesized compounds were elucidated by FT-IR, 1H and 13C NMR and Mass spectral analysis.

A highly efficient and selective Pd/C-catalyzed ligand-free cyclocarbonylation reaction for the synthesis of flavones has been developed. Various flavone derivatives were isolated in excellent yields with excellent functional group tolerances. Additionally, catalyst reuse experiments were performed successfully as well.

Coumarin and flavone derivatives are highly valuable molecules in drug discovery. Here, two new regioselective cross-dehydrogenation couplings of coumarins and flavones with different ethers via C(sp(3))-H functionalization processes were developed, generating new ether-substituted derivatives not previously reported. These reactions proceeded well via radical mechanisms and provided the corresponding products in good yields.

Three new flavone derivatives, paranicflavones A–C (1–3), together with three known similar compounds (4–6), were isolated from their roots and stems of Tiandeng tobacco. Their structures were elucidated by spectroscopic methods, including extensive 1H and 13C NMR techniques. Additionally, compounds 1–6 were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities, and compound 2 exhibited anti-TMV activity with inhibition rate of 35.8%, which is higher than that of positive control, ningnanmycin.

Flavones have antioxidant, anti-proliferative, anti-tumor, anti-microbial, estrogenic, acetyl cholinesterase, anti-inflammatory activities and are also used in cancer, cardiovascular disease, neurodegenerative disorders, etc. Also, flavonoids are found to have an effect on several mammalian enzymes like protein kinases that regulate multiple cell signaling pathways and alterations in multiple cellular signaling pathways are frequently found in many diseases. Flavones have been an indispensable anchor for the development of new therapeutic agents. The majority of metabolic diseases are speculated to originate from oxidative stress, and it is therefore significant that recent studies have shown the positive effect of flavones on diseases related to oxidative stress. Due to the wide range of biological activities of flavones, their structure-activity relationships have generated interest among medicinal chemists. The outstanding development of flavones derivatives in diverse diseases in very short span of time proves its magnitude for medicinal chemistry research. The present review gives detail about the structural requirement of flavone derivatives for various pharmacological activities. This information may provide an opportunity to scientists of medicinal chemistry discipline to design selective, optimize as well as poly-functional flavone derivatives for the treatment of multi-factorial diseases.

An efficient and practical method for effecting a tandem C-H alkenylation/C-O cyclization has been achieved via the C-H functionalization of flavone derivatives. The synthetic utility of the one-pot sequence was demonstrated by obtaining convenient access to coumarin-annelated benzopyrans. The reaction scope for the transformation was found to be fairly broad, affording good yields of a wide range of flavone- or coumarin-fused benzopyran motifs, which are privileged structures in many biologically active compounds.

Background: Most of the available antimicrobial drugs have developed resistance; some of them suffer from severe toxicity, side effects. So, there is a need to discover novel compound(s) which should not only be potent, but also less toxic and cost effective. Objectives: The aim of the study is to develop new synthetic antimicrobial agents (Anti-bacterial and anti-fungal) such as 3-substituted flavone/flavanone derivatives, which should be significantly potent with low toxicity. Method: An attempt was made to synthesize a newer series of 3-methyl flavanone derivatives together with the synthesis of a series of 3-hydroxyl flavone analogues. The structures of the test compounds were elucidated and established by UV, IR, H-NMR1, C-NMR13 and mass spectrometry. The synthesized compounds were subjected for in vitro antimicrobial screening using cup plate methods, followed by the determination of zone of inhibitions. Results: Two series (each 10) of 3-methyl flavanone and 3-hydroxy flavone derivatives were synthesized. The structures of the test compounds were characterized and established by various spectroscopic methods. The synthesized compounds were screened for in vitro antibacterial and antifungal activity against different strains (3- Gram positive, 3-Gram negative and 2-fungal strains). Conclusion: Some of the 3-hydroxyl flavones derivatives (1b, 3b, 4b, and 5b) and 3-methyl flavanone derivatives (3a, 1a, 2a and 4a) were found to elicit potent antimicrobial activity. The study revealed that 3-hydroxy flavone derivatives were found to be most active against Gram negative, while 3-methyl flavanone derivatives were active against Gram positive bacteria.

A novel and regioselective ammonium iodide mediated CS bond formation protocol involving flavones and sulfonyl chlorides to generate different ArS-substituted flavone derivatives in high yields was developed. Different from existing metal-free CS bond formation protocols with the use of PPh3 or I2 as the catalyst, this method provides an alternative way of constructing CS bonds through the use of NH4I as a catalyst, which makes it highly valuable for the efficient synthesis of thioether compounds.

A palladium-catalyzed oxidative arylation of chromones was examined. A regioselective 2-arylation of chromone was carried out via a double C–H activation process. The procedure provided an expedient approach for the preparation of flavone derivatives.

Two new acylated flavone C-glycosides, 6''-O-(2'''-methylbutyryl)isoswertisin (1) and 6''-O-(2'''-methylbutyryl)isoswertiajaponin (2), together with four known acylated flavone C-glycosides, were isolated for the first time from the whole plants of Hemistepta lyrata (Compositae). Their structures were elucidated on the basis of chemical and spectroscopic methods including HR-ESI-MS, ESI-MS, UV, IR, and 1D and 2D NMR spectral techniques.

An expeditious synthesis of three polyoxygenated flavones mosloflavone, negletein and baicalein. starting from crysin, an easily available flavone, by a bromination/methoxylation procedure is reported The convergent synthesis exploits a base induced Wesley-Moser type rearrangement (C) 2009 Elsevier Ltd All rights reserved

We establish useful models that relate experimentally measured biological activities of compounds to their molecular structure. The pED50 feeding inhibition on Spodoptera litura species exhibited by aurones, chromones, 3-coumarones and flavones is analyzed in this work through the hypothesis encompassed in the Quantitative Structure?Activity Relationships (QSAR) Theory. This constitutes a first necessary computationally based step during the design of more bio-friendly repellents that could lead to insights for improving the insecticidal activities of the investigated compounds.After optimizing the molecular structure of each furane and pyrane benzoderivative with the semiempirical molecular orbitals method PM3, more than a thousand of constitutional, topological, geometrical and electronic descriptors are calculated and multiparametric linear regression models are established on the antifeedant potencies. The feature selection method employed in this study is the Replacement Method, which has proven to be successful in previous analyzes. We establish the QSAR both for the complete molecular set of compounds and also for each chemical class, so that acceptably describing the variation of the inhibitory activities from the knowledge of their structure and thus achieving useful predictive results. The main interest of developing trustful QSAR models is that these enable the prediction of compounds having no experimentally measured activities for any reason. Therefore, the structure?activity relationships are further employed for investigating the antifeedant activity on previously synthesized 2-,7-substituted benzopyranes, which do not pose any measured values on the biological expression. One of them, 2-(α-naphtyl)-4H-1-benzopyran-4-one, results in a promising structure to be experimentally analyzed as it has predicted pED50=1.162. Fil: Duchowicz, Pablo Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Goodarzi, Mohammad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina Fil: Ocsachoque, Marco Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas ; Argentina Fil: Romanelli, Gustavo Pablo. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales. Departamento de Ciencias Exactas. Catedra de Quimica Organica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas ; Argentina Fil: Ortiz, Erlinda del Valle. Universidad Nacional de Catamarca. Facultad de Tecnologia y Ciencias Aplicadas; Argentina. Comision Nacional de Investigacion Cientifica y Tecnologica; Chile Fil: Autino, Juan C.. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales. Departamento de Ciencias Exactas. Catedra de Quimica Organica; Argentina Fil: Bennardi, Daniel Oscar. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales. Departamento de Ciencias Exactas. Catedra de Quimica Organica; Argentina Fil: Ruiz, Diego Manuel. Universidad Nacional de La Plata. Facultad de Ciencias Agrarias y Forestales. Departamento de Ciencias Exactas. Catedra de Quimica Organica; Argentina Fil: Castro, Eduardo Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina

A novel C-glycosylflavone with unusual alpha-orientation at the anomeric center of d-glucose was isolated from the leaves of Diospyros kaki. Its structure was determined as 8-C-[alpha-l-rhamnopyranosyl-(1 --4)]-alpha-d-glucopyranosylapigenin by chemical methods and spectral experiments.

A new acylated flavone glycoside, echioidinin 2'-O-beta-D-(2''-O-acetyl)glucopyranoside (1) along with the three known flavonoids, 5,6,7,8,5'-pentamethoxy-3',4'-methylenedioxyflavone (2), 5,2',6'-trihydroxy-7-methoxyflavone (3), and kaempferol 7,4'-dimethyl ether 3-O-beta-D-glucopyranoside (4), were isolated from the roots of Colebrookea oppositifolia. The structure of compound 1 was elucidated by extensive spectral and chemical studies.

Quantitative structure–activity relationship (QSAR) has been established for 32 oxime- and methyloxime-containing flavone and isoflavone derivatives having antiproliferative activity. Multiple linear regressions were used to generate the relationship between biological activity and calculated descriptors. Model with good statistical qualities was developed using the software VLIFE MDS 2.0. Validation of the model was done by cross-validation, randomization, and external test set prediction. On the basis of the QSAR model, we designed a new series of compounds and calculated the activity and found that the compounds were more potent than the existing compounds. QSAR studies of flavone and isoflavone derivatives. The negative coefficient of SdOi indicated that its increase is detrimental to antiproliferative activity. The positive coefficient of QMDMg showed that the magnitude of dipole is responsible for the activity.

A novel and highly regioselective ammonium iodide-induced nonradical sulfenylation method for the construction of a C–S bond was developed via C–H functionalization. With DMSO or R1SO2NHNH2 as a sulfenylating agent, MeS- and R1S-substituted flavone derivatives were obtained in good yields. This method enriches current C–S bond formation chemistry, making it a highly valuable and practical method in pharmaceutical industry.

Two new flavonosides have been isolated from the roots of Glychirriza glabra and identified as 5,8-dihydroxy-flavone-7-O-beta-D-glucuronide, glychionide A, and 5-hydroxy-8-methoxyl-flavone-7-O-beta-D-glucuronide, glychionide B.

Scutellarin-7-O-glucuronide (1) has been synthesized from 2-hydroxyl-4,5,6-trimethoxyacetophenone through eight steps, including Michael addition, cyclization, hydrogenation, hydroxyl protection, deprotection, etc. The overall yield of 13% is much higher than that reported (0.6%) by L. Farkas, G. Mezey-Vàndor et al. in 1974.

In a chemical investigation on the flavone composition of Leonurus heterophyllus a new flavonoside has been isolated. By means of physico-chemical evidences and spectral analysis its structure has been established as quercetin-3-O-[3-(4-hydroxy-3,5-dimethoxybenzyl)-alpha-L-rhamnopyranosyl]-(1--6)-beta-D-galactopyranoside (1).

The twigs of Dorstenia angusticornis and Dorstenia barteri var. subtriangularis yielded 16 compounds. Two novel diprenylated chalcones: 3,5′-di-(2-hydroxy-3-methylbut-3-enyl)-4,2′,4′-trihydroxychalcone, 3, 4-(2,2-dimethylpyrano)-3′-(2-hydroxy-3-methylbut-3-enyl)-2′,4′-dihydroxychalcone and the known stipulin were isolated from both species. 3-(2-Hydroxy-3-methylbut-3-enyl)-5′-(3,3-dimethylallyl)-4,2′,4′-trihydroxychalcone and the known compounds: 4-hydroxylonchocarpin, kanzonol B, bartericins A, B, C and 3′-(2-hydroxy -3-methylbut-3-enyl)-4,2′,4′-trihydroxychalcone were isolated from D. barteri while the known compounds: gancaonin Q, paratocarpins C, F, and lupeol were obtained from Dorstenia angusticornis . β-Sitosterol and its β- d -glucopyranoside were isolated from both species. Structures of these secondary metabolites were established using spectroscopic analysis, especially, NMR spectra in conjunction with 2D experiments, COSY, HMQC and HMBC.

Ab initio and DFT conformational analysis was performed on the flavone derivatives chrysin (5,7-dihydroxyflavone; 2-phenyl-5,7-dihydroxy-4H-1-benzopyran-4-one) and 7,8-dihydroxyflavone (2-phenyl-7,8-dihydroxy-4H-1-benzopyran-4-one). The structural features required for optimal stabilization in each molecule were identified. It was discovered that sparsely placed hydroxyl groups, particularly with hydrogen bond-like interactions, resulted in lowering the potential energy minimum for the molecules. It was also noted that one of the factors capable of destroying co-planarity was steric interference between closely placed functional groups across the phenyl and the benzo-γ-pyrane ring. Studies performed on the radical forms of the flavonoids, however, showed that the unpaired electron is confined only to the benzo-γ-pyrane ring, and not delocalized across the phenyl ring.Key words: flavonoid, flavone, chrysin, ab initio conformational analysis, anti-oxidant, free radical, 5,7-dihydroxy flavone, 7,8-dihydroxyflavone.

Various 3-halo flavones were prepared by reaction of the corresponding flavone derivatives with R4NBr/PhI(OAc)2 system under mild reaction conditions.

An efficient and practical method for effecting a tandem C-H alkenylation/C-O cyclization has been achieved via the C-H functionalization of flavone derivatives. The synthetic utility of the one-pot sequence was demonstrated by obtaining convenient access to coumarin-annelated benzopyrans. The reaction scope for the transformation was found to be fairly broad, affording good yields of a wide range of flavone- or coumarin-fused benzopyran motifs, which are privileged structures in many biologically active compounds.

Flavones have antioxidant, anti-proliferative, anti-tumor, anti-microbial, estrogenic, acetyl cholinesterase, anti-inflammatory activities and are also used in cancer, cardiovascular disease, neurodegenerative disorders, etc. Also, flavonoids are found to have an effect on several mammalian enzymes like protein kinases that regulate multiple cell signaling pathways and alterations in multiple cellular signaling pathways are frequently found in many diseases. Flavones have been an indispensable anchor for the development of new therapeutic agents. The majority of metabolic diseases are speculated to originate from oxidative stress, and it is therefore significant that recent studies have shown the positive effect of flavones on diseases related to oxidative stress. Due to the wide range of biological activities of flavones, their structure-activity relationships have generated interest among medicinal chemists. The outstanding development of flavones derivatives in diverse diseases in very short span of time proves its magnitude for medicinal chemistry research. The present review gives detail about the structural requirement of flavone derivatives for various pharmacological activities. This information may provide an opportunity to scientists of medicinal chemistry discipline to design selective, optimize as well as poly-functional flavone derivatives for the treatment of multi-factorial diseases.

Semiempirical quantum-chemical calculations were used to study the reactivity of the C2 = C3 bond in flavones in reaction with hydroxyl radical. The preferred pathway was found to be addition of the radical by C3. Increased reactivity in the reaction in question of the hydroxy groups on C3 and C4' in polyhydroxyflavones was revealed.

A simple and convenient one-pot strategy for the prepa ration of thioflavones from 1,3-diketones is described. Cyclodehydration of a range of β-diketones and thionation of the resulting flavones was achieved using thiophosphoryl chloride (PSCl 3 ) which serves as both a catalyst and thionating agent.

New 2′-hydroxychalcone and flavone derivatives have been synthesised. Their [1H] and [13C] NMR spectra were assigned by the application of COSY and HETCOR experiments and allowed the discussion of some structural aspects. It was shown on the basis of NOE experiments some configurational and conformational features of both type of compounds.

Six flavone derivatives were studied. Previously reported NMR data of three of these derivatives were corrected and the NMR data for the other three derivatives not studied previously were completely assigned on the basis of the basic 1D and 2D NMR experiments and molecular modeling.

Human protein kinase CK2 is one of the most intriguing enzymes, which functional role still remains unclear despite of decades of studying. At present there is abundant evidence pointing to the fact that inhibitors of CK2 could be used as pharmaceutical agents to treat cancer, viral infections and inflammatory diseases. Here we report novel synthetic flavone inhibitors, 4′-hydroxyflavones, possessing high activity towards CK2. These compounds were identified with receptor-based virtual screening and then chemically optimized on the base of rationale derived from biochemical screening and molecular modeling. It has been demonstrated that synthetic flavone derivatives are much more potent CK2 inhibitors than the natural ones, and we believe that their further examination will be helpful for studying biological role of CK2 as well as for development of new kinase-oriented drugs.

A number of free radical generating systems were used to investigate the antioxidant properties and structure-activity relationships of a series of monohydroxylated and dihydrox­ylated flavones. Ortho-dihydroxylated flavones showed the highest inhibitory activity on en­ zymic and non-enzymic microsomal lipid peroxidation as well as on peroxyl radical scaveng­ing. Most flavones were weak scavengers of hydroxyl radical, while ortho-dihydroxylated flavones interacted with superoxide anion generated by an enzymic system or by human neutrophils. This series of compounds did not exert cytotoxic effects on these cells. Scaveng­ing of superoxide and peroxyl radicals may determ ine the antioxidant properties of these active flavones.

A palladium-catalyzed oxidative arylation of chromones was examined. A regioselective 2-arylation of chromone was carried out via a double C–H activation process. The procedure provided an expedient approach for the preparation of flavone derivatives.

All newly synthesized benzofurans (I), furochromones (II), and flavones (III) as well as selected intermediates are evaluated for their anticonvulsant activity using both scPTZ and MES tests.