Phenolic cyclisation. Part I. Novel synthesis of 1-substituted isoquinoline and spiro[cycloalkane-1,1′-isoquinoline] derivatives and its application to the total synthesis of isoquinoline alkaloids

Kametani, Tetsuji; Fukumoto, K.; Agui, Hideo; Yagi, H.; Kigasawa, Kazuo; Sugahara, Hiroshi; Hiiragi, Mineharu; Hayasaka, Tomoaki; Ishimaru, H.

doi:10.1039/j39680000112

Cited by 27 publications

(11 citation statements)

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“…The N-alkylation of isatin and its analogues has also been reported [48]. For the synthesis of the hydroxylated compounds (1a-q, 2a-q and 3a,b), the phenolic Pictet-Spengler reaction, earlier described by Kametani et al [47], was found to be quite useful as it proceeded smoothly under relatively mild conditions of heating in ethanol. This reaction generally provided two positional isomers, the 6-hydroxy (2a-q) and 8-hydroxy (1a-q) compounds, in variable ratios.…”

Section: Resultsmentioning

confidence: 99%

“…The target compounds were synthesized by the Pictet-Spengler reaction of a substituted phenethylamine with isatin or a substituted isatin. The precursors, 3,4-dimethoxyphenethylamine and 3,4,5trimethoxyphenethylamine were prepared as previously described for related amphetamine analogues [46], while 3-hydroxyphenethylamine was obtained from the demethylation of commercially available 3-methoxyphenethylamine [47]. The N-alkylation of isatin and its analogues has also been reported [48].…”

Section: Resultsmentioning

confidence: 99%

“…The compounds were synthesized by the phenolic Pictet-Spengler reaction reported by Kametani et al [47] and modified by Ngo Hanna et al [52] (scheme 2b). In a typical experiment, crude 3hydroxyphenethylamine (0.9 g, 6.6 mmol, 1 equiv), obtained as described in Method A above, and the appropriate isatin (1 equiv, 6.6 mmol) were dissolved in absolute ethanol (10 ml) and triethylamine (1 ml) was added.…”

Section: Synthesis Of 57-dibromoisatin (7c) (Methods C)mentioning

confidence: 99%

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3′,4′-Dihydro-2′H-spiro[indoline-3,1′-isoquinolin]-2-ones as potential anti-cancer agents: synthesis and preliminary screening

Lobe

Efange

2020

R. Soc. open sci.

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Both tetrahydroisoquinolines (THIQs) and oxindoles (OXs) display a broad range of biological activities including anti-cancer activity, and are therefore recognized as two privileged scaffolds in drug discovery. In the present study, 24 3′,4′-dihydro-2′H-spiro[indoline-3,1′-isoquinolin]-2-ones, designed as molecular hybrids of THIQ and OX, were synthesized and screened in vitro against 59 cell lines in the NCI-60 screen. Twenty compounds displayed weak to moderate inhibition of cell proliferation; among them, three compounds displayed at least 50% inhibition of cell proliferation. The compounds appeared to target primarily renal cell cancer lines; however, leukaemia, melanoma, non-small cell lung cancer, prostate, ovarian and even breast cancer cell lines were also affected. Therefore, this class of spirooxindoles may provide useful leads in the search for new anti-cancer agents.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Synthesis Of 57-dibromoisatin (7c) (Methods C)mentioning

confidence: 99%

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3′,4′-Dihydro-2′H-spiro[indoline-3,1′-isoquinolin]-2-ones as potential anti-cancer agents: synthesis and preliminary screening

Lobe

Efange

2020

R. Soc. open sci.

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“…Initially the Pictet‐Spengler cyclisation was attempted using the standard conditions reported previously, involving reflux of phenylephrine with benzaldehyde in ethanol. Under these conditions no reaction was observed.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline

et al. 2017

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Condensation of phenylephrine with different aldehydes, under Pictet‐Spengler cyclisation conditions, afforded a series of tetrahydroisoquinoline derivatives as mixtures of cis/trans isomers. Single crystal X‐ray analysis of the dibenzoate derivative of one of the 4‐nitrophenyl isomers confirmed it to be the trans isomer. The conformation of the cis isomer was determined through computational experiments and comparison of the predicted and observed 1H NMR spectra, particularly the magnitude of the coupling constants. Fourteen tetrahydroisoquinoline derivatives were then evaluated for their activity towards T. b. rhodesiense, two strains of P. falciparum, and mammalian cells. The most promising derivative, the undecyl derivative, showed good activity towards T. b. rhodesiense with an IC50 value in the sub‐micromolar range and good selectivity over mammalian cells. The same derivative also showed activity against both strains of P. falciparum with IC50 values in the low micromolar range.

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“…5 ) The reaction does not employ acid catalyst as used in Pictet-Spengler reaction caracteristically, where the closed ring is due to only density and required a hydroxyl group at the ortho for the closing part. Similar condensation has also been reported by Cohen.…”

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confidence: 99%

Syntheses of Isoquinolines by Condensation of Dopamine with Carbonyl Compounds

Morita

Itô

Tono

1975

Agricultural and Biological Chemistry

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Phenolic cyclisation. Part I. Novel synthesis of 1-substituted isoquinoline and spiro[cycloalkane-1,1′-isoquinoline] derivatives and its application to the total synthesis of isoquinoline alkaloids

Cited by 27 publications

References 0 publications

3′,4′-Dihydro-2′H-spiro[indoline-3,1′-isoquinolin]-2-ones as potential anti-cancer agents: synthesis and preliminary screening

3′,4′-Dihydro-2′H-spiro[indoline-3,1′-isoquinolin]-2-ones as potential anti-cancer agents: synthesis and preliminary screening

Synthesis, Stereochemistry and Antiparasitic Activity of Derivatives of (4R)-4,6-Dihydroxy-N-methyl-1,2,3,4-tetrahydroisoquinoline

Syntheses of Isoquinolines by Condensation of Dopamine with Carbonyl Compounds

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