Pyrrolidine-Mediated Direct Preparation of (E)-Monoarylidene Derivatives of Homo- and Heterocyclic Ketones with  Various Aldehydes

Gu, Xin; Wang, Xiaoyan; Wang, Fengtian; Sun, Hongbao; Liu, Jie; Xie, Yongmei; Xiang, Mingli

doi:10.3390/molecules19021976

Cited by 5 publications

(10 citation statements)

References 42 publications

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“…Compound 4 was prepared according to Typical procedure 1 from ( E )-3-benzylideno-1-metylopiperyd-4-one (0.392 g, 1.95 mmol) [ 55 ] and ( E )-cinnamoyl cyanide (0.346 g, 2.2 mmol) [ 25 ] and purified by flash column chromatography (AcOEt:Hex, 30:70) to yield a pink solid (0.588 g, 91%).…”

Section: Methodsmentioning

confidence: 99%

Curcumin and Its New Derivatives: Correlation between Cytotoxicity against Breast Cancer Cell Lines, Degradation of PTP1B Phosphatase and ROS Generation

Kostrzewa

Wołosewicz

Jamrozik

et al. 2021

IJMS

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Breast cancer is the most common cancer of women—it affects more than 2 million women worldwide. PTP1B phosphatase can be one of the possible targets for new drugs in breast cancer therapy. In this paper, we present new curcumin derivatives featuring a 4-piperidone ring as PTP1B inhibitors and ROS inducers. We performed cytotoxicity analysis for twelve curcumin derivatives against breast cancer MCF-7 and MDA-MB-231 cell lines and the human keratinocyte HaCaT cell line. Furthermore, because curcumin is a known antioxidant, we assessed antioxidant effects in its derivatives. For the most potent cytotoxic compounds, we determined intracellular ROS and PTP1B phosphatase levels. Moreover, for curcumin and its derivatives, we performed real-time microscopy to observe the photosensitizing effect. Finally, computational analysis was performed for the curcumin derivatives with an inhibitory effect against PTP1B phosphatase to assess the potential binding mode of new inhibitors within the allosteric site of the enzyme. We observed that two tested compounds are better anticancer agents than curcumin. Moreover, we suggest that blocking the -OH group in phenolic compounds causes an increase in the cytotoxicity effect, even at a low concentration. Furthermore, due to this modification, a higher level of ROS is induced, which correlates with a lower level of PTP1B.

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Section: Methodsmentioning

confidence: 99%

Curcumin and Its New Derivatives: Correlation between Cytotoxicity against Breast Cancer Cell Lines, Degradation of PTP1B Phosphatase and ROS Generation

Kostrzewa

Wołosewicz

Jamrozik

et al. 2021

IJMS

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“…1 H NMR (500 MHz, chloroform-d) δ 6.68 (t, J = 7.5 Hz, 1H), 4.51 (s, 2H), 3.96 (t, J = 6.1 Hz, 2H), 2.53 (t, J = 6.1 Hz, 2H), 2.03 (p, J = 7.5 Hz, 2H), 1.03 (t, J = 7.5 Hz, 3H). 13 (13); 41 (31); 42 (18); 43 (16); 53 (33); 54 (17); 55 (52); 56 (19); 66 (12); 67 (43); 68 (14); 69 (15); 81 (13); 83 (100); 84 (14); 95 (15); 97 (12); 111 (11); 112 (51); 140 (7) [M] + . Anal…”

Section: -Propylidenedihydro-2h-pyran-4(3h)-one (4eb)unclassified

“…1 H NMR (500 MHz, DMSO-d 6 ) δ 7.47 (s, 6H), 4.61 (s, 2H), 3.69 (s, 2H), 2.58 (t, J = 6.3 Hz, 2H), 1.50−1.17 (m, 9H). 13 (42); 42 (18); 43 (13); 44 (16); 53 (10); 55 (12); 56 (18); 57 (100); 67 (14); 81 (38); 96 (16); 109 (29); 122 (11); 137 (18); 139 (14); 166 (16); 183 (31); 239 (6) [M] + . Anal (16), 41 (100), 42 (25), 43 (45), 44 (30), 51 (12), 53 (28), 55 (35), 56 (30), 57 (83), 65 (15), 67 (28), 68 (13), 77 (29), 78 (10), 79 (36), 80 (21), 81 (25), 82 (98), 83 (14), 91 (24), 93 (18), 94 (13), 95 (10), 97 (10), 98 (15), 99 (13), 107 (12), 108 (15), 109 (10), 110 (26), 111 (10), 121 (12), 122 (19), 135 (15), 136 (11) tert-Butyl 3-Benzylidene-5-methyl-4-oxopiperidine-1-carboxylate (4jf).…”

Section: Tert-butyl 3-(cyclohexylmethylene)-4-oxopiperidine-1-carboxy...mentioning

confidence: 99%

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Toward a Chemical Constructor: A Lego-Like Approach for Formal α-Alkylation of Cyclic Ketones

Frolov,

Chuchvera,

Ostapchuk

et al. 2024

J. Org. Chem.

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A conceptual strategy for a formal α-alkylation of α-methylene ketones was developed. Diverse 1°and 2°alkyl substituents were generated in the α-position of various ketones via synthesis of enaminone (step 1) and treatment with organomagnesium (step 2) with subsequent catalytic hydrogenation (step 3, 1°alkyl) or organocopper reagents (step 4, 2°alkyl). Tolerance toward ester, Boc-protected amine, and α-fluoro-substituted ketone moieties was demonstrated. The suitability of the method for late-stage natural product modification was shown.

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“…However, literature search revealed that synthetic methodologies that can be applied to the preparation of 3-alkylidenetetrahydropyran-4-ones 1 with diverse substitution patterns are limited. There are several methods which enable the introduction of arylidene group onto the plain tetrahydropyran-4-one ring using a reaction with aromatic aldehydes in the presence of catalytic amount of TMSNMe 2 and MgBr 2 Et 2 O [7] or pyrrolidine [8]. There are also two literature reports which describe preparation of specific 3-methylidenetetrahydropyran-4-ones, and thus 8-methylidene-9oxo-6-oxaspiro [5,6] decane was prepared by carbocyclization of unsaturated thioesters under palladium catalysis [9] and 2-butyl-6,6-dimethyl-3-methylidenetetrahydropyran-4-one was obtained in a three-step reaction sequence starting from 6-ethoxy-2-methyl-5-diphenylphosphorylhex-3-yn-5-en-2-ol [10].…”

Section: Chemistrymentioning

confidence: 99%

Synthesis of 2,2,6-Trisubstituted 5-Methylidene-tetrahydropyran-4-ones with Anticancer Activity

et al. 2020

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In our continuous search for new, relatively simple 2-alkylidene-1-oxoheterocycles as promising anticancer drug candidates, herein we report an efficient synthesis of 2,2,6-trisubstituted 5-methylidenetetrahydropyran-4-ones. These compounds were obtained in a four step reaction sequence, in which starting diethyl 2-oxopropylphosphonate was transformed into 2,2-disubstituted 5-diethoxyphosphoryldihydropyran-4-ones, followed by Michael addition of various Grignard reagents and Horner-Wadsworth-Emmons reaction of the obtained adducts with formaldehyde. Stereochemistry of the intermediate Michael adducts is also discussed. Final 5-methylidenetetrahydropyran-4-ones were tested for their possible antiproliferative effect against three cancer cell lines and 6-isopropyl-2,2-dimethyl-5-methylidenetetrahydropyran-4-one (11c), which showed very high cytotoxic activity against HL-60 human leukemia cells and was three times more active than known anticancer drug carboplatin, was selected for further biological evaluation, in order to disclose its mechanism of action. The obtained results indicated that 11c induced apoptosis in HL-60 cells and caused the arrest of the cell cycle in the G2/M phase, which may suggest its cytotoxic and cytostatic activity.

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Pyrrolidine-Mediated Direct Preparation of (E)-Monoarylidene Derivatives of Homo- and Heterocyclic Ketones with Various Aldehydes

Cited by 5 publications

References 42 publications

Curcumin and Its New Derivatives: Correlation between Cytotoxicity against Breast Cancer Cell Lines, Degradation of PTP1B Phosphatase and ROS Generation

Curcumin and Its New Derivatives: Correlation between Cytotoxicity against Breast Cancer Cell Lines, Degradation of PTP1B Phosphatase and ROS Generation

Toward a Chemical Constructor: A Lego-Like Approach for Formal α-Alkylation of Cyclic Ketones

Synthesis of 2,2,6-Trisubstituted 5-Methylidene-tetrahydropyran-4-ones with Anticancer Activity

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