Synthesis of Flavones and γ‐Benzopyranones Using Mild Sonogashira Coupling and 18‐Crown‐6 Ether Mediated 6‐<i>endo</i> Cyclization

Chuang, Da Wei; El-Shazly, Mohamed; Balaji, D Barve; Chung, Yu Ming; Chang, Fang Rong; Wu, Yang Chang

doi:10.1002/ejoc.201200529

Cited by 25 publications

(10 citation statements)

References 44 publications

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“…The remaining ten known flavones were identified by interpretation of their 1D and 2D NMR, HRESIMS and UV spectral data and comparison with data available in the literature, including 3′-methoxyflavone ( 1 ) 21 , flavone ( 2 ) 22 , 2′-methoxyflavone ( 3 ) 21 , 2′,5′-dimethoxyflavone ( 4 ) 20 , 3′-hydroxy-4′,5′-dimethoxyflavone ( 6 ) 20 , 5,6,2′,6′-tetramethoxyflavone ( 7 ) 20 , 5,6,2′,3′,6′-pentamethoxyflavone ( 8 ) 23 , 3′-hydroxyflavone ( 9 ) 24 , 2′-hydroxyflavone ( 10 ) 24 , 5,6,2′-trimethoxyflavone ( 12 ) 25 . Their 1 H and 13 C NMR data are shown in Tables 1–3 in supplementary information.…”

Section: Resultsmentioning

confidence: 99%

Unusual Flavones from Primula macrocalyx as Inhibitors of OAT1 and OAT3 and as Antifungal Agents against Candida rugosa

Xue

Wang

et al. 2019

Sci Rep

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A bioactivity guided program exploring the interaction of phytochemicals in the entire plant Primula macrocalyx with the organic anion transporters (OAT1 and OAT3) and microorganisms led to the elucidation of ten known flavones ( 1 – 4 , 6 – 10 , 12 ) and two previously undescribed flavones ( 5 , 11 ). The structures of the compounds were determined by extensive analysis of spectroscopic data, as well as by comparison with data from previous reports. Two known flavones ( 9 , 12 ) are reported for the first time from the family Primulaceae. All compounds were evaluated for inhibition of OAT1 and OAT3. Six flavones ( 2 , 3 , 6 – 8 , 12 ) showed potent inhibitory activity on OAT1, while seven flavones ( 2 , 3 , 6 – 9 , 12 ) showed marked inhibitory activity on OAT3, with IC 50 ≤ 10.0 µ M. Antimicrobial activities of crude fractions against sixteen microorganisms were tested to give a target yeast strain Candida rugosa for further evaluation of MICs on the isolates. Three flavones ( 7 , 8 , 12 ) showed marked antifungal activity with MIC < 2.0 µ M. To our knowledge, this study is the first to evaluate these flavones as inhibitors of the OAT1 and OAT3, and as antifungal agents.

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Section: Resultsmentioning

confidence: 99%

Unusual Flavones from Primula macrocalyx as Inhibitors of OAT1 and OAT3 and as Antifungal Agents against Candida rugosa

Xue

Wang

et al. 2019

Sci Rep

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“…Our synthetic strategy toward the anticipated deuterium-labeled compounds involved continuous-flow deuteration of the corresponding ynone analogs of antiabetic chalcones 1 – 4 (Scheme 1). Ynones 5 – 9 were prepared by literature procedures through the coupling of acid chlorides with terminal acetylenes under Sonogashira conditions: PdCl 2 (PPh 3 ) 2 /CuI as a catalyst and Et 3 N as a base in THF as solvent (Scheme 2) [66,67,68]. The mixtures were stirred for 1 h at room temperature (RT) under a N 2 atmosphere, and ynones 5 – 9 were achieved in excellent yields after simple extractive work-up and chromatographic purification (see Experimental Section).…”

Section: Resultsmentioning

confidence: 99%

“…The combined organic layers were dried over Na 2 SO 4 and concentrated under reduced pressure. The residue obtained was purified by column chromatography on silica gel, with a mixture of n -hexane/EtOAc as eluent; ynones 5 ‒ 9 were achieved in yields of 83%‒92% [66,67,68].…”

Section: Methodsmentioning

confidence: 99%

Continuous-Flow Synthesis of Deuterium-Labeled Antidiabetic Chalcones: Studies towards the Selective Deuteration of the Alkynone Core

Ötvös

Hsieh

et al. 2016

Molecules

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Flow chemistry-based syntheses of deuterium-labeled analogs of important antidiabetic chalcones were achieved via highly controlled partial C≡C bond deuteration of the corresponding 1,3-diphenylalkynones. The benefits of a scalable continuous process in combination with on-demand electrolytic D2 gas generation were exploited to suppress undesired over-reactions and to maximize reaction rates simultaneously. The novel deuterium-containing chalcone derivatives may have interesting biological effects and improved metabolic properties as compared with the parent compounds.

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“…The 1,4–addition of diethylamine (10 equiv) to O ‐TBS protected alkynones in EtOH or sodium 2‐pyridinethiolate (1 equiv) to o ‐(alkynon‐1‐yl)phenols in THF afforded the corresponding enaminoketone or β‐(2‐pyridylthio)phenoxide intermediates, respectively, which underwent intramolecular cyclization to give flavones at reflux temperature. The treatment of o ‐alkynoylphenyl acetates with CH 3 OK (2.5 equiv) using 18‐crown‐6 (2.5 equiv) in THF provided the corresponding phenoxide intermediates, which underwent cyclization and subsequent leaving of methoxy group to give flavones …”

Section: Methodsmentioning

confidence: 94%

Synthesis of Flavones by Thallium(III) p‐tosylate‐catalyzed Regioselective Cyclization of o‐(Alkynon‐1‐yl)phenols

Lee

Kim

2018

Bulletin Korean Chem Soc

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Flavones are important classes of flavonoids and have been isolated from a wide variety of plants, fruits, and vegetables. 1 They have attracted considerable interests due to their diverse pharmacological properties on human health, including antioxidant, anti-inflammatory, anticancer, antifungal, and antimicrobial activities. 2 A number of methods for synthesizing flavones have been reported, 3 which can be mainly classified as cyclodehydration of 1-(2-hydroxyphenyl)-3-phenyl-1,3-propanediones, 4 oxidative cyclization of 2 0 -hydroxychalcones, 5 and carbonylative cyclization of o-iodophenols with arylacetylenes in the presence of palladium catalyst. 6 Recently, the cyclization of o-(alkynon-1-yl)phenols has been investigated as a convenient method of flavone synthesis. However, the intramolecular cyclization of o-(alkynon-1-yl)phenols produced not only flavones via 6-endo-digonal cyclization (path a) but also aurones via 5-exo-digonal cyclization (path b) and the ratio of products was highly dependent on the kinds of reagents and solvents (Scheme 1).The reaction of o-(alkynon-1-yl)phenols and K 2 CO 3 (0.2 equiv) in refluxing acetone afforded products of both 6-endo and 5-exo cyclization as the major of 6-endo mode, while 5-exo cyclization became enhanced when ethanol was used as protic media. 7 The use of triflic acid 8 (1 equiv) in 1,2-dichloroethane or 4-(dimethylamino)pyridine 9 (0.1 equiv) in DMF on the cyclization of o-(alkynon-1-yl)phenols predominantly induced 6-endo cyclization to provide flavones. The 1,4-addition of diethylamine 10 (10 equiv) to O-TBS protected alkynones in EtOH or sodium 2-pyridinethiolate 11 (1 equiv) to o-(alkynon-1-yl)phenols in THF afforded the corresponding enaminoketone or β-(2-pyridylthio)phenoxide intermediates, respectively, which underwent intramolecular cyclization to give flavones at reflux temperature. The treatment of oalkynoylphenyl acetates with CH 3 OK (2.5 equiv) using 18-crown-6 (2.5 equiv) in THF provided the corresponding phenoxide intermediates, which underwent cyclization and subsequent leaving of methoxy group to give flavones. 12 However, the use of PBu 3 13 (0.05 equiv) in EtOH or Cs 2 CO 3 14 (3 equiv) in acetone on the cyclization of o-(alkynon-1-yl)phenols induced the 5-exo cyclization with a high regioselectivity to give aurones. The treatment of o-(alkynon-1-yl)phenols with AgNO 3 15 (0.3 equiv) in CH 3 OH or AgOAc 16 (0.03 equiv) in DMF also induced high 5-exo cyclization via dual-coordination process to give aurones. The reaction of o-(alkynon-1-yl)phenols and sodium 2-pyridyloxide (0.1 equiv) in THF provided the corresponding sodium phenoxides, which underwent 5-exo cyclization kinetically to give aurones after protonation by 2-PyOH. 17 As an extension of our studies on the synthesis of flavones, 11,18 we herein report that flavones can be synthesized by regioselective cyclization of o-(alkynon-1-yl)phenols using 0.05 equiv of thallium(III) p-tosylate in CH 3 OH. Thallium(III) p-tosylate has been utilized for the conversion of flavanones to isoflavo...

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Synthesis of Flavones and γ‐Benzopyranones Using Mild Sonogashira Coupling and 18‐Crown‐6 Ether Mediated 6‐endo Cyclization

Cited by 25 publications

References 44 publications

Unusual Flavones from Primula macrocalyx as Inhibitors of OAT1 and OAT3 and as Antifungal Agents against Candida rugosa

Unusual Flavones from Primula macrocalyx as Inhibitors of OAT1 and OAT3 and as Antifungal Agents against Candida rugosa

Continuous-Flow Synthesis of Deuterium-Labeled Antidiabetic Chalcones: Studies towards the Selective Deuteration of the Alkynone Core

Synthesis of Flavones by Thallium(III) p‐tosylate‐catalyzed Regioselective Cyclization of o‐(Alkynon‐1‐yl)phenols

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