Quercetin (=2‐(3,4‐Dihydroxyphenyl)‐3,5,7‐trihydroxy‐4H‐1‐ benzopyran‐4‐one) Glycosides and Sulfates: Chemical Synthesis,Complexation, and Antioxidant Properties

Glycosides, acylated glycosides, and sulfates of quercetin (=3,3′,4′,5,7‐pentahydroxyflavone; 1 ), which is, together with its derivatives, among the most common polyphenols found in plants and in the human diet, were prepared and quantitatively investigated for their ability to bind metal ions (Al^III, Fe^II, Fe^III), enhance and vary natural colours (anthocyanin copigmentation), and trap potentially damaging radicals (antioxidant activity).     

Sesquiterpenoids and 2‐(2‐Phenylethyl)‐4H‐chromen‐4‐one (=2‐(2‐Phenylethyl)‐4H‐1‐benzopyran‐4‐one) Derivatives from Aquilaria malaccensis Agarwood

The four new sesquiterpenoids 1 – 4 , and the new 2‐(2‐phenylethyl)‐4H‐chromen‐4‐one (=2‐(2‐phenylethyl)‐4H‐1‐benzopyran‐4‐one) derivative 5 , together with the two known sesquiterpenoids 6 and 7 , the five known chromenones 8 – 12 , and 1‐hydroxy‐1,5‐diphenylpentan‐3‐one ( 13 ), were isolated from a 70% MeOH extract of Aquilaria malaccensis agarwood chips. Their structures were elucidated on the basis of comprehensive spectral analyses and comparison with literature data.     

Eight New 2‐(2‐Phenylethyl)chromone (=2‐(2‐Phenylethyl)‐4H‐1‐benzopyran‐4‐one) Derivatives from Aquilaria malaccensis Agarwood

Eight new and eight known 2‐(2‐phenylethyl)chromone (=2‐(2‐phenylethyl)‐4H‐1‐benzopyran‐4‐one) derivatives, i.e., 1 – 8 and 9 – 16 , respectively, together with the two known sesquiterpenoids 17 and 18 were isolated from a 70% MeOH extract of Aquilaria malaccensis (AM) agarwood chips. Their structures were determined based on extensive spectroscopic analysis and comparison with reported data.     

Synthesis and Chemical Reactivity of 4‐Oxo‐4H‐1‐benzopyran‐3‐carboxaldehyde

4‐Oxo‐4H‐1‐benzopyran‐3‐carboxaldehyde (chromone‐3‐carboxaldehyde or 3‐formylchromone) 1 is an important biologically active compound. It can serve as a precursor in the synthesis of a wide range of heterocyclic systems having chromone moiety, many of which exhibit broad spectrum of biological activities such as anti‐mutagenisity, cytotoxicity, thymidine phosphorylase inhibitor, and anti‐HIV activity. During the last decade, the title compound was studied extensively. The review presents an overall survey of the synthesis, chemical reactivity, and biological activities of 4‐oxo‐4H‐1‐benzopyran‐3‐carboxaldehydes and some of its derivatives.     

Two Rare α‐Pyrone (=2H‐Pyran‐2‐one) Derivatives from Gentiana rhodantha Franchet

Two new rare α‐pyrone (=2H‐pyran‐2‐one) derivatives, rhodanthpyrones A and B ( 1 and 2 , resp.), together with fourteen known compounds, 3 – 16 , were isolated from the whole plants of Gentiana rhodantha. The structures of these compounds were elucidated by spectroscopic analyses. This is the first report on the occurrence of α‐pyrone derivatives in the genus Gentiana.     

Efficient Synthesis of Novel Coumarin‐3‐carboxamides (=2‐Oxo‐2H‐1‐benzopyran‐3‐carboxamides) Containing Lipophilic Spacers

The novel coumarin‐3‐carboxamides (=2‐oxo‐2H‐1‐benzopyran‐3‐carboxamides) 5a – 5g containing lipophilic spacers were synthesized through the Ugi‐four‐component reaction (Scheme 1). The reactions of aromatic aldehydes 1 , 4,4′‐oxybis[benzenamine] or 4,4′‐methylenebis[benzenamine] as diamine 2 , coumarin‐3‐carboxylic acid (=2‐oxo‐2H‐benzopyran‐3‐carboxylic acid; 3 ), and alkyl isocyanides 4 lead to the desired substituted coumarin‐3‐carboxamides 5a – 5g at room temperature with high bond‐forming efficiency. These novel coumarin derivatives exhibit brilliant fluorescence at 544 nm in CHCl₃.     

Three polymorphs of 3‐(3‐phenyl‐1H‐1,2,4‐triazol‐5‐yl)‐2H‐1‐benzopyran‐2‐one formed from different solvents

The polymorphic study of 3‐(3‐phenyl‐1H‐1,2,4‐triazol‐5‐yl)‐2H‐1‐benzopyran‐2‐one, C₁₇H₁₁N₃O₂, was performed due to its potential biological activity and revealed three polymorphic modifications in the triclinic space group P, the monoclinic space group P2₁ and the orthorhombic space group Pbca. These polymorphs have a one‐column layered type of crystal organization. The strongest interactions between the molecules of the studied structures is stacking between π‐systems, while N—H…N and C—H…O hydrogen bonds link stacked columns forming layers as a secondary basic structural motif. C—H…π hydrogen bonds were observed between neighbouring layers and their role is the least significant in the formation of the crystal structure. Packing differences between the polymorphic modifications are minor and can be identified only using an analysis based on a comparison of the pairwise interaction energies.     

Synthesis and Characterization of Novel 1‐Methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazole Derivatives

A series of novel 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles was synthesized in three steps from 5‐(1‐methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones. 5‐(1‐Methyl‐1H‐indazol‐3‐yl)‐4‐phenyl‐2H‐1,2,4‐triazole‐3(4H)‐thiones were converted into 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles upon methylation followed by treatment with aq. KMnO₄. The reaction of 1‐methyl‐3‐(5‐(methylsulfonyl)‐4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles with Raney nickel resulted in desulphonylation to afford corresponding 1‐methyl‐3‐(4‐phenyl‐4H‐1,2,4‐triazol‐3‐yl)‐1H‐indazoles. All the new synthesized compounds were characterized by spectral techniques.     

A Novel and Efficient Synthesis of 3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐ones (=3‐[(4,5‐Dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐1‐benzopyran‐2‐ones)

An efficient one‐pot synthesis of 3‐[(4,5‐dihydro‐1H‐pyrrol‐3‐yl)carbonyl]‐2H‐chromen‐2‐one (=3‐[(4,5‐dihydro‐1H‐pyrrol‐3yl)carbonyl]‐2H‐1‐benzopyran‐2‐one) derivatives 4 by a four‐component reaction of a salicylaldehyde 1 , 4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one, a benzylamine 2 , and a diaroylacetylene (=1,4‐diarylbut‐2‐yne‐1,4‐dione) 3 in EtOH is reported. This new protocol has the advantages of high yields (Table), and convenient operation. The structures of these coumarin (=2H‐1‐benzopyran‐2‐one) derivatives, which are important compounds in organic chemistry, were confirmed spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS) and by elemental analyses. A plausible mechanism for this reaction is proposed (Scheme 2).     

Synthesis of Acetyl and Iodo Derivatives of 4‐Hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c]pyridine‐2,5‐diones and 4‐Hydroxy‐1‐phenylpyridin‐2(1H)‐ones

A simple and efficient method has been described for the synthesis of acetyl and iodo derivatives of 4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 1 and 4‐hydroxy‐1‐phenylpyridin‐2(1H )‐ones 5 . Compounds 1 with phenyl and alkyl substituent at C(7) and C(8), respectively, can be easily acetylated by refluxing in a mixture of acetic acid and polyphosphoric acid to give 3‐acetyl‐4‐hydroxy‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 2 in excellent yields. Compounds 1 and 5 can be iodinated with iodine and anhydrous sodium carbonate in boiling dioxane to give 4‐hydroxy‐3‐iodo‐6‐phenyl‐6H‐pyrano[3,2‐c ]pyridine‐2,5‐diones 3 and 4‐hydroxy‐3‐iodo‐1‐phenylpyridin‐2(1H )‐ones 6 , respectively, in good yields. The structures were confirmed using infrared, nuclear magnetic resonance , and elemental analysis.     

Four Novel Dihydroisocoumarin (=3,4‐Dihydro‐1H‐2‐benzopyran‐1‐one) Glucosides from the Fungus Cephalosporium sp. AL031

Four novel dihydroisocoumarin (=3,4‐dihydro‐1H‐2‐benzopyran‐1‐one) glucosides were isolated from a culture broth of a strain of the fungus Cephalosporium sp. AL031. Their structures were elucidated as (2E,4E)‐5‐[(3S)‐5‐acetyl‐8‐(β‐D ‐glucopyranosyloxy)‐3,4‐dihydro‐6‐hydroxy‐1‐oxo‐1H‐2‐benzopyran‐3‐yl]penta‐2,4‐dienal ( 1 ), (2E,4E)‐5‐[(3S)‐5‐acetyl‐8‐(β‐D ‐glucopyranosyloxy)‐3,4‐dihydro‐6‐methoxy‐1‐oxo‐1H‐2‐benzopyran‐3‐yl]penta‐2,4‐dienal ( 2 ), (3S)‐8‐(β‐D ‐glucopyranosyloxy)‐3‐[(1E,3E,5E)‐hepta‐1,3,5‐trienyl]‐3,4‐dihydro‐6‐hydroxy‐5‐methyl‐1H‐2‐benzopyran‐1‐one ( 3 ), and (3S)‐8‐[(6‐O‐acetyl‐β‐D ‐glucopyranosyl)oxy]‐3‐[(1E,3E,5E)‐hepta‐1,3,5‐trienyl]‐3,4‐dihydro‐6‐methoxy‐5‐methyl‐1H‐2‐benzopyran‐1‐one ( 4 ) by spectroscopic methods, including 2D‐NMR techniques and chemical methods.     

Stereoselective Synthesis of (3R)‐3,4‐Dihydro‐6,8‐dimethoxy‐3‐undecyl‐ 1H‐[2]benzopyran‐1‐one and Derivatives,Metabolites from Ononis natrix

A short stereoselective synthesis of (3R)‐3,4‐dihydro‐6,8‐dimethoxy‐3‐undecyl‐1H‐[2]benzopyran‐1‐one and derivatives isolated from Ononis natrix has been described. Condensation of dodecanoyl chloride with 3,5‐dimethoxyhomophthalic acid afforded 6,8‐dimethoxy‐3‐undecylisocoumarin 3 , which, on sequential saponification and esterification, yielded the keto ester 5 . Enantioselective reduction of 5 with TarB‐NO₂/LiBH₄ directly furnished the title dihydroisocoumarin 1a in 80% ee (82% yield). Partial as well as complete demethylation of the latter provided the dihydroisocoumarins 1b and 1c , respectively. Diastereotopy of the CH₂ H‐atoms on either side of the stereogenic center (C(3)) and the mass‐fragmentation pattern of the dihydroisocoumarins have also been described. All of the compounds synthesized were examined in vitro for antifungal activity.     

7‐Hydr­oxy‐6‐methoxy‐3‐[(2‐oxo‐2H‐1‐benzopyran‐7‐yl)oxy]‐2H‐1‐benzopyran‐2‐one

The title compound, daphnoretin, C₁₉H₁₂O₇, was isolated from the leaves of Stellera chamaejasme L. Two independent mol­ecules are present in the asymmetric unit, with similar conformations. Each of the independent mol­ecules is composed of two chromene systems connected by an ether bridge. The dihedral angles between the mean planes of the two chromene systems are 86.9 (2) and 81.9 (3)°. Mol­ecules form chains via hydrogen bonds and adjacent chains are parallel to each other.     

Synthesis and Antioxidant Properties of New Substituted 8‐Methyl‐6‐phenyl‐5,6‐dihydro‐4H‐1,3,2‐benzodioxaphosphocine‐2‐oxide Derivatives

A new route for the synthesis of substituted 8‐methyl‐6‐phenyl‐5,6‐dihydro‐4H‐1,3,2‐benzodioxaphosphocine‐2‐oxide derivatives has been developed by using cinnamic acid and p‐cresol via condensation, reduction, and followed by phosphorylation steps. The title compounds were characterized by IR, ¹H, ¹³C, ³¹P, and mass spectral studies and elemental analysis. The title compounds have been investigated for their antioxidant activity with respect to their IC₅₀ values using 2,2‐diphenyl‐1‐picrylhydrazyl, NO radical scavenging activities, and reducing power assay. The results obtained from the aforementioned methods revealed that 2‐phenylamino derivatives have shown greater free radical scavenging activity when compared with those of the phenoxy derivatives and is attributed to the presence of secondary amino group, which is able to produce free radicals easily.     

Synthesis of Isoxazole, 1, 2, 4‐Oxadiazole and (1H‐Pyrazol‐4‐yl)‐methanone Oxime Derivatives from N‐Hydroxy‐1H‐pyrazole‐4‐carbimidoyl Chloride and their Biological Activity

Some novel isoxazole‐, 1,2,4 oxadiazole‐, and (1H‐pyrazol‐4‐yl)‐methanone oxime derivatives were synthesized from N‐hydroxy‐1H‐pyrazole‐4‐carbimidoyl chloride and the structures of all products were identified by spectral data (¹H‐NMR, ¹³C‐NMR, IR, MS, and HRMS) and evaluated their antibacterial activity.     

1‐Hydroxy‐1H‐benzo[d][1,2,6]oxazaborinin‐4(3H)‐one

The structure of the title compound, C₇H₆BNO₃, a new boron heterocycle, prepared by the condensation of (2‐ethoxycarbonylphenyl)boronic acid and hydroxylamine, reveals the specific mode of intramolecular condensation between a phenylboronic acid and an ortho hydroxamic acid substituent. The crystal structure shows that dehydration occurs to form a planar oxazaborinine ring possessing both phenol‐like B—O—H and lactam functional groups. In the extended structure, intermolecular hydrogen bonding generates a 14‐membered ring. To our knowledge, this is the first crystal structure determination involving a six‐membered ring that exhibits consecutive B—OH, O, NH, and C=O functional groups.     

Synthesis of 4‐Arylisocoumarins (=4‐Aryl‐1H‐2‐benzopyran‐1‐ones) through Acidic Hydrolysis of (Z)‐2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehydes,Followed by Oxidation

4‐Arylisocoumarins (=4‐aryl‐1H‐2‐benzopyran‐1‐ones) 6 were prepared from 2‐(1‐aryl‐2‐methoxyethenyl)‐1‐bromobenzenes 1 . Successive treatment of these bromo styrenes with BuLi and 1‐formylpiperidine gave a mixture of (E)‐ and (Z)‐2‐(1‐aryl‐2‐methoxyethenyl)benzaldehydes 2 . Hydrolysis of (Z)‐isomers with conc. HBr, followed by pyridinium chlorochromate (PCC) oxidation of the resulting 1H‐2‐benzopyran‐1‐ol derivatives 4 (and 5 ), afforded the desired products.     

Synthesis and Antimicrobial Activity of 2‐(Pyridine‐3‐yl)‐4H‐chromen‐4‐one Derivatives

An efficiently synthesis of chromones via cyclodehydration of corresponding 1‐(2‐hydroxyphenyl)‐3‐(pyridine‐3‐yl)propane‐1,3‐dione is described under ultrasound irradiation. A series of novel 2‐(pyridine‐3‐yl)‐4H‐chromen‐4‐one derivatives was confirmed on the basis of ¹H‐NMR, mass, IR spectral data, and elemental analysis. The synthesized compounds were evaluated for their antibacterial and antifungal activities. Most of the compounds were found to be comparable potent than the reference standard drugs. Utilization of ultrasound irradiation, simple reaction conditions, isolation, and purification makes this manipulation very interesting from an economic and environmental perspective.     

An Efficient Synthesis of 3‐(1H‐Tetrazol‐5‐yl)coumarins (=3‐(1H‐Tetrazol‐5‐yl)‐2H‐1‐benzopyran‐2‐ones) via Domino Knoevenagel Condensation,Pinner Reaction,and 1,3‐Dipolar Cycloaddition in Water

A novel straightforward synthesis of 3‐(1H‐tetrazol‐5‐yl)coumarins (=3‐(1H‐tetrazol‐5‐yl)‐2H‐1‐benzopyran‐2‐ones) 6 via domino Knoevenagel condensation, Pinner reaction, and 1,3‐dipolar cycloaddition of substituted salicylaldehydes (=2‐hydroxybenzaldehydes), malononitrile (propanedinitrile), and sodium azide in H₂O is reported (Scheme 1 and Table 2). This general protocol provides a wide variety of 3‐(1H‐tetrazol‐5‐yl)coumarins in good yields under mild reaction conditions.