Catalytic asymmetric synthesis of the common amino acid component in the biosynthesis of tetrahydroisoquinoline alkaloids

Tanifuji, Ryo; Oguri, Hiroki; Koketsu, Kento; Yoshinaga, Yuki; Minami, Atsushi; Oikawa, Hideaki

doi:10.1016/j.tetlet.2015.12.110

Cited by 10 publications

(6 citation statements)

References 37 publications

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“…Resveratrol standard was purchased from Sigma Aldrich (Steinheim, Germany). Resveratrol derivatives (RD1-RD5) were obtained starting from commercially available aromatic aldehydes (vanilline, isovanilline, and syringaldehyde) and the easily preparable known aldehyde 10 [ 34 ]. The hydroxy groups of vanilline, isovanilline, and syringaldehyde were protected as benzyl ethers 1, 4, and 9.…”

Section: Methodsmentioning

confidence: 99%

Akt/mTOR Targeting Activity of Resveratrol Derivatives in Non-Small Lung Cancer

et al. 2022

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The Akt-mTOR signal is important for the survival and proliferation of cancer cells and has become an interesting drug target. In this study, five resveratrol derivatives were evaluated for anticancer activity and Akt/mTOR targeting activity in non-small lung cancer cell lines. The effects of resveratrol derivatives on cell proliferation were assessed by 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, nucleus staining, and colony formation assay. Furthermore, the effect of resveratrol derivatives on proliferation-related protein expression was analyzed by immunofluorescence and Western blotting. For the structure–activity relationship (SAR), results reveal that two derivatives of resveratrol which are 4,4′-(ethane-1,2-diyl) bis(2-methoxyphenol) (RD2) and the 4-(3-hydroxy-4-methoxyphenethyl)-2-methoxyphenol (RD3) had very similar structures but exerted different cytotoxicity. The IC50 of RD2 and RD3 were 108.6 ± 10.82 and more than 200 µM in the A549 cell line and 103.5 ± 6.08 and more than 200 µM in H23 cells, respectively. RD2 inhibited cell proliferation and induced apoptosis when compared with the control, while RD3 caused minimal effects. Cells treated with RD2 exhibited apoptotic nuclei in a concomitant with the reduction of cellular p-Akt and p-mTOR. RD3 had minimal effects on such proteins. According to these results, molecular docking analysis revealed a high-affinity interaction between RD2 and an Akt molecule at the ATP-binding and the allosteric sites, indicating this RD2 as a potential Akt inhibitor. This study provides useful information of resveratrol derivatives RD2 for treating lung cancer via Akt/mTOR inhibition.

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Section: Methodsmentioning

confidence: 99%

Akt/mTOR Targeting Activity of Resveratrol Derivatives in Non-Small Lung Cancer

et al. 2022

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“…To a solution of 3-methylcatechol (51.9 mg, 0.40 mmol) and benzyl bromide (142 mL, 1.19 mmol) in dry DMF (540 mL), 2-(Benzyloxy)-6-methylphenol (25). 43,44 To a solution of 3methylcatechol (1.08 g, 8.73 mmol) and benzyl bromide (1.14 mL, 9.61 mmol) in dry DMF (10 mL) and dry acetone (4 mL), K 2 CO 3 (3.70 g, 26.2 mmol) was added, and stirring for 4 h at rt. The ltrate was diluted with diethyl ether, washed with 1 N of HCl, dried over Na 2 SO 4 , ltered and the solvent was evaporated.…”

Section: General Methodsmentioning

confidence: 99%

“…Formylation of 25 at the 5-position was then achieved via the Duff reaction using hexamethylenetetramine (HMTA). 43,44 The aldehyde derivative 9c was then obtained by benzylation at the 2-position of the hydroxy group. Quercetin analogues 2 and 3 were synthesised with the resulting 9b and 9c, respectively, by the same scheme used to obtain dimethylquercetin (1) (Scheme 6).…”

Section: Design and Synthesis Of Quercetin Analoguesmentioning

confidence: 99%

Synthesis of methylated quercetin analogues for enhancement of radical-scavenging activity

et al. 2017

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“…The engineered biosynthesis of functionalized tyrosine derivative 7 has not been achieved yet, to our knowledge, while the biosynthetic enzymes responsible for the conversion of l -tyrosine into 7 have been suggested. , To secure a sufficient amount of 7 , a catalytic asymmetric synthetic route was developed . We previously investigated the SfmC-catalyzed assembly of the tetracyclic scaffold (Scheme ).…”

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confidence: 99%

“…17,18 To secure a sufficient amount of 7, a catalytic asymmetric synthetic route was developed. 19 We previously investigated the SfmCcatalyzed assembly of the tetracyclic scaffold (Scheme 1). Employment of N-myristoylated peptidyl aldehyde 8, assumed to be liberated from the upstream module SfmB, markedly In addition to issues with the substrate tolerance, a major obstacle for postenzymatic chemical conversions could be the removal of the peptidyl side chain to access saframycins (1, 2) and their congeners.…”

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confidence: 99%

Chemo-enzymatic Total Syntheses of Jorunnamycin A, Saframycin A, and N-Fmoc Saframycin Y3

et al. 2018

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The antitumor tetrahydroisoquinoline (THIQ) alkaloids share a common pentacyclic scaffold that is biosynthesized by nonribosomal peptide synthetases involving unique enzymatic Pictet-Spengler cyclizations. Herein we report concise and divergent chemo-enzymatic total syntheses of THIQ alkaloids by merging precise chemical synthesis with in vitro engineered biosynthesis. A recombinant enzyme SfmC responsible for the biosynthesis of saframycin A was adapted for the assembly of these natural products and their derivatives, by optimizing designer substrates compatible with SfmC through chemical synthesis. The appropriately functionalized pentacyclic skeleton were efficiently synthesized by streamlining the linkage between SfmC-catalyzed multistep enzymatic conversions and chemical manipulations of the intermediates to install aminonitrile and N-methyl groups. This approach allowed rapid access to the elaborated pentacyclic skeleton in a single day starting from two simple synthetic substrates without isolation of the intermediates. Further functional group manipulations allowed operationally simple and expeditious syntheses of jorunnamycin A, saframycin A, and N-Fmoc saframycin Y3 that could be versatile and common precursors for the artificial production of other antitumor THIQ alkaloids and their variants.

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Catalytic asymmetric synthesis of the common amino acid component in the biosynthesis of tetrahydroisoquinoline alkaloids

Abstract: Please cite this article as: Tanifuji, R., Oguri, H., Koketsu, K., Yoshinaga, Y., Minami, A., Oikawa, H., Catalytic asymmetric synthesis of the common amino acid component in the biosynthesis of tetrahydroisoquinoline alkaloids, Tetrahedron Letters (2015), doi: http://dx.

Cited by 10 publications

References 37 publications

Akt/mTOR Targeting Activity of Resveratrol Derivatives in Non-Small Lung Cancer

Akt/mTOR Targeting Activity of Resveratrol Derivatives in Non-Small Lung Cancer

Synthesis of methylated quercetin analogues for enhancement of radical-scavenging activity

Chemo-enzymatic Total Syntheses of Jorunnamycin A, Saframycin A, and N-Fmoc Saframycin Y3

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