A New Pyrone Derivative from Fungus Cephalosporium sp. AL031

Cephalosporium sp. AL031 is a fungus isolated from Sinarundinaria nitida grown in the Ailao Mountain, Yunnan, China. It produces, in cultures, antibacterial and fungicidal secondary metabolites, according to the antimicrobial activity test1. In previous p…     

Two new dihydroisocoumarins from the fungus Cephalosporium sp. AL031

Two new dihydroisocoumarins, 3,4-dihydro-3-heptantrienyl-8-hydroxyl-6-hydroxymethyl-5-methylisocoumarin and 6-acetoxymethylene-3,4-dihydro-3-heptantrienyl-8-hydroxyl-5-methylisocoumarin were isolated from a culture broth of a strain of the fungus, Cephalosporium sp. AL031. Their structures were elucidated by interpretation of their spectroscopic data.     

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).     

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.     

A novel antioxidant isobenzofuranone derivative from fungus Cephalosporium sp.AL031

Bioassay-guided fractionation of metabolites from the fungus Cephalosporium sp.AL031 isolated from Sinarundinaria nitida led to the discovery of a new isobenzofuranone derivative, 4,6-dihydroxy-5-methoxy-7-methylphthalide (1), together with three known compounds: 4,5,6-trihydroxy-7-methyl-1,3-dihydroisobenzofuran (2), 4,6-dihydroxy-5-methoxy-7-methyl-1,3-dihydroisobenzofuran (3) and 4,5,6-trihydroxy-7-methylphthalide (4). The structure of the new compound 1 was determined based on MS, 1D and 2D NMR spectral data. Compounds 1-4 showed potent antioxidant activity with EC?? values of 10, 7, 22 and 5 μM by 1,1-diphenyl-2-picryhydrazyl (DPPH) radical-scavenging assay.     

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.     

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.     

Synthesis and Photochromic Behaviour of Novel 2H‐1‐Benzopyrans (=2H‐Chromenes) Derived from Carbazololes

The synthesis and photochromic properties of new 2,2‐diphenyl‐2H‐1‐benzopyrans, fused to an indole moiety, are described. All compounds exhibit photochromic behaviour in solution at room temperature. The heteroanellation effects are variable and depend on the position and geometry of the fused indole moiety. A general bathochromic shift in the spectra of the open forms is observed. The presence of a N‐methyl group prevents the broadening of the absorption spectra and promotes the instability of some photoinduced forms of compounds with the indole moiety fused at the 5,6 positions of the 2H‐1‐benzopyran skeleton. The enhanced photocolouration efficiency in the near‐UV and the kinetics of thermal bleaching indicate that the novel compounds with an indole moiety fused at the 6,7 positions, particularly those with a linked thiophene moiety, are very interesting molecules for applications in the field of variable optical absorption systems.     

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).     

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.     

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.     

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.     

The Structures of Indazolin‐3‐one (=1,2‐Dihydro‐3H‐indazol‐3‐one) and 7‐Nitroindazolin‐3‐one

The existence of polymorphism in parent indazolin‐3‐one (=1,2‐dihydro‐3H‐indazol‐3‐one; 1 ) is reported as well as an X‐ray and NMR CPMAS study establishing that its 7‐nitro derivative 2 exists as the 3‐hydroxy tautomer. Absolute shieldings calculated at the GIAO/B3LYP/6‐311++G(d,p) level were used to determine the tautomeric oxo/hydroxy equilibrium in solution, i.e., always the 1H‐indazol‐3‐ol tautomer predominates.     

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 Properties of 2,3‐Dihydro‐1H‐corannuleno[2,3‐cd]pyridine (=2,3‐Dihydro‐1H‐dibenzo[1,10 : 6,7]fluorantheno[3,4‐cd]pyridine) Derivatives: Heterocyclic peri‐Anellated Corannulenes

The anellation of a 6‐membered ring to the 2,3‐position of corannulene (=dibenzo[ghi,mno]fluoranthene; 1 ) leads to curved aromatic compounds with a significantly higher bowl‐inversion barrier than corannulene (see Fig. 1). If the bridge is −CH₂−NR−CH₂−, a variety of linkers can be introduced at the N(2) atom, and the corresponding curved aromatics act as versatile building blocks for larger structures (see Scheme). The locked bowl, in combination with an amide bond (see 9 and 10 ), gives rise to corannulene derivatives with chiral ground‐state conformations, which possess the ability to adapt to their chiral environment by shifting their enantiomer equilibrium slightly in favor of one enantiomeric conformer. Rim annulation of corannulene seems to display a significantly lower electron‐withdrawing effect than facial anellation on [5,6]fullerene‐C₆₀‐I_h, as determined by an investigation of the basicity at the N‐atom of CH₂−NR−CH₂ (see 4 vs. 15 in Fig. 2).     

Water‐Soluble Flavonol (=3‐Hydroxy‐2‐phenyl‐4H‐1‐benzopyran‐4‐one) Derivatives: Chemical Synthesis,Colouring, and Antioxidant Properties

Water‐soluble derivatives of rutin, a very common glycoside of quercetin (=3,3′,4′,5,7‐pentahydroxyflavone=2‐(3,4‐dihydroxyphenyl)‐3,5,7‐trihydroxy‐4H‐1‐benzopyran‐4‐one) and a potent plant antioxidant from the flavonol family, were synthesized by simple chemical procedures aimed at introducing carboxy or sulfo groups at the sugar moiety (Scheme 1). Such derivatives form stable molecular complexes with malvin, a polyphenolic pigment from the anthocyanin family, and thereby prove to be very effective in the enhancement (hyperchromism) and variation (bathochromism) of natural colours. The H₂O‐solubilizing carboxylate and sulfate groups are shown to deeply modify the enthalpy‐entropy balance of the pigment‐flavonol complexation (copigmentation). A molecular interpretation of the complexation‐induced bathochromic shift in the pigment VIS band is proposed. Finally, the H₂O‐soluble rutin derivatives are shown to retain the high antioxidant ability of rutin as evidenced by their efficient trapping of the coloured radical DPPH (=2,2‐diphenyl‐1‐(2,4,6‐trinitrophenyl)hydrazyl).     

On the Reactions of Furan‐2,3‐diones with Oxindole (=1,3‐Dihydro‐2H‐indol‐2‐one) and Lawesson Reagent. Synthesis of New 1,3‐Dihydro‐2H‐indol‐2‐ones,Bis‐furanones,and Bis‐pyrrolones

Lactone analogues of 3‐substituted oxindoles (=1,3‐dihydro‐2H‐indol‐2‐ones) and nonbenzoid oxa‐analogous isoindigoid or nonbenzoid isoindigoid dyes were prepared by the reactions of furan‐2,3‐diones with oxindole and Lawesson reagent (Schemes 1 and 3), respectively. So, new derivatives of 2‐oxobutanoic acid, bis‐furanone, and bis‐pyrrolone, which are potentially biologically active compounds, were synthesized for the first time.     

1,3‐Dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐one

A facile acid catalysed cyclisation method for the preparation of the cyclic urea 2H‐imidazo[4,5‐c]pyridin‐2‐one ( 2 ) in > 95 % yield is reported. The biologically active compound 2 can be obtained by heating (3‐amino‐4‐pyridinyl)‐carbamic acid methyl, ethyl or tert‐butyl esters ( 1a‐c ) in sulfuric acid (0.1 %) or in aqueous HBF₄ (3.5 equivalents) for 10 min. ‐ 3 hrs at 90 °C. The corresponding microwave‐promoted (MW) reactions afforded the pure product 2 within few minutes. The 6‐butylamino‐substituted analogue ( 2a ) was correspondingly obtained by MW irradiation in 99 % yield by cyclisation of 2‐(butylamino)‐5‐amino‐4‐pyridylcarbamic acid isopropyl ester ( 1d ). Quantitative precipitation of product 2 was obtained by pH adjustment. The process represents a solvent‐free, “green” method for the preparation of 2 .