A convenient approach to an advanced intermediate toward the naturally occurring, bioactive 6-substituted 5-hydroxy-4-aryl-1H-quinolin-2-ones

Larghi, Enrique L.; Kaufman, Teodoro S.

doi:10.1039/c5ob02680f

Cited by 20 publications

(8 citation statements)

References 111 publications

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“…2a ) 20 – 25 . Simonetti and co-workers developed a convenient way to install 6-propenyl side chain by Claisen rearrangement of 5- O -allyl in the heterocycle 21 . Similar reaction was also used in the construction of unsaturated pyran fragments in yaequinolones J1 and J2 26 by Vece and co-workers 22 , as well as the synthesis of aniduquinolone C and peniprequinolone by Christmann’s group 23 .…”

Section: Introductionmentioning

confidence: 99%

Scalable total synthesis of (+)-aniduquinolone A and its acid-catalyzed rearrangement to aflaquinolones

Guo

Mou

et al. 2022

Commun Chem

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The strong antibacterial, antiviral and anticancer activities demonstrated by quinolones make them promising lead structures and important synthetic targets for drug discovery. Here, we report, to the best of our knowledge, the first scalable total synthesis of antiviral (+)-aniduquinolone A, possessing a 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one skeleton. This synthetic strategy explores E-stereoselective Horner–Wadsworth–Emmons (HWE) olefination as the key step to assemble isopropenyl substituted tetrahydrofuran onto the 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one core, which is built by highly diastereoselective intramolecular aldol reaction. Moreover, two sets of stereoisomers of aniduquinolone A with substantially overlapping NMR data were synthesized completely and assigned unambiguously by comprehensive analysis of both their spectroscopic and X-ray diffraction data. Unexpectedly, aflaquinolones A, C, and D that feature different 2,4-dimethyl cyclohexanone moieties were transformed successfully from (+)-aniduquinolone A by treating with TFA. The methodology delineated herein can be applied broadly to the synthesis of natural alkaloids containing the core structure of 3,4-dioxygenated 5-hydroxy-4-aryl-quinolin-2(1H)-one.

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Section: Introductionmentioning

confidence: 99%

Scalable total synthesis of (+)-aniduquinolone A and its acid-catalyzed rearrangement to aflaquinolones

Guo

Mou

et al. 2022

Commun Chem

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“…2c ). For example, reduction of the NO 2 group in 4b followed by an intramolecular ester-to-amide exchange could give lactam 4b-1 that bears a quinolone core widely found in natural products and bioactive molecules 35 . The alkene in allylic alcohol 4b could be easily converted to epoxide 4b-2 in 87% yield with excellent stereo-selectivity (only one diastereoisomer was obtained).…”

Section: Resultsmentioning

confidence: 99%

Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process

Wang

Proctor

et al. 2016

Nat Commun

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Benzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron-transfer (SET) process for radical reactions. Representative recent progress includes α-carbon benzylation of ketones and aldehydes via photoredox catalysis. Here we disclose the generation of (nitro)benzyl radicals via N-heterocyclic carbene (NHC) catalysis under reductive conditions. The radical intermediates generated via NHC catalysis undergo formal 1,2-addition with ketones to eventually afford tertiary alcohol products. The overall process constitutes a formal polarity-inversion of benzyl bromide, allowing a direct coupling of two initially electrophilic carbons. Our study provides a new carbene-catalysed reaction mode that should enable unconventional transformation of (nitro)benzyl bromides under mild organocatalytic conditions.

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“…Quinolinones 6g and 6h underwent Claisen rearrangement at 150 °C in 1,2-dichlorobenzene for 10 hours to give 12a and 12b in 71% and 63% yield, respectively (Scheme 3). 22 At higher temperature and prolonged reaction time, elimination of the tertiary alcohol was observed. Olefin metathesis of 12a using Umicore M71SIMes as catalyst and an excess of 2-methylbut-2ene gave (±)-aniduquinolone C (13a) 21 in 81% yield, whereas (±)-peniprequinolone (13b) 20 was obtained in 80% yield starting from 12b.…”

Section: Scheme 2 Intramolecular Aldolizationmentioning

confidence: 98%

Synthesis of Quinolinone Alkaloids via Aryne Insertions into Unsymmetric Imides in Flow

et al. 2018

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A general strategy for the synthesis of 3,4-dioxygenated quinolin-2-one natural products is reported. The key step is a regioselective insertion of arynes into unsymmetric imides. When performed in continuous flow, the reaction proceeded within minutes. The resulting N-acylated 2-aminobenzophenones were transformed to (±)-peniprequinolone, (±)-aflaquinolones E and F, (±)-6-deoxyaflaquinolone E, (±)-quinolinones A and B, and (±)-aniduquinolone C in 1-3 steps. 4 d MeCN CsF 3.7:1 33 5 d,e MeCN KF 4.0:1 20 a Reaction conditions: 4a (0.26 mmol, 1 equiv.), 3a (0.39 mmol, 1.5 equiv.), Fsource (0.52 mmol, 2 equiv.), solvent (2.0 mL), 60 °C, 16 h; b ratios were determined by 1 H NMR integration; c isolated yield; d conducted at 80 °C for 4 h; e 18-crown-6 (1 equiv.) and 4 Å mol sieves were used as additives. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website.

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A convenient approach to an advanced intermediate toward the naturally occurring, bioactive 6-substituted 5-hydroxy-4-aryl-1H-quinolin-2-ones

Cited by 20 publications

References 111 publications

Scalable total synthesis of (+)-aniduquinolone A and its acid-catalyzed rearrangement to aflaquinolones

Scalable total synthesis of (+)-aniduquinolone A and its acid-catalyzed rearrangement to aflaquinolones

Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process

Synthesis of Quinolinone Alkaloids via Aryne Insertions into Unsymmetric Imides in Flow

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