Structural Revision and Biomimetic Synthesis of Goupiolone B

Matsuo, Yosuke; Yoshida, Ayane; Saito, Yoshinori; Tanaka, Takashi

doi:10.1002/anie.201706532

Cited by 15 publications

(9 citation statements)

References 34 publications

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“…87) Furthermore, reaction of 3a with the benzotropolone ring of 12 affords flavanotheaflavin A (45). 88) The reactions disclosed in these studies are now applied to structural revision and biomimetic synthesis of biologically active polyphenols, goupiolones A and B. Other compounds produced by oxidation of benzotropolone moiety are shown in Fig.…”

Section: 3 Production and Degradation Of Theaflavinsmentioning

confidence: 99%

Production Mechanisms of Black Tea Polyphenols

Tanaka

Matsuo

2020

Chem. Pharm. Bull.

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Black tea accounts for 70-80% of world tea production, and the polyphenols therein are produced by enzymatic oxidation of four tea catechins during tea fermentation. However, only limited groups of dimeric oxidation products, such as theaflavins, theasinensins, and theacitrins, have been isolated from black tea and chemically characterized. This is largely because of the complexity and heterogeneity of the oxidation products. To determine structures and production mechanisms of uncharacterized black tea polyphenols, in vitro model fermentation experiments using pure catechins and polyphenol oxidase have been applied, and basic oxidation mechanisms have been established. Contemporary methods, such as LC-MS, are also effective to identify catechin oxidation products in black tea. Despite ongoing efforts, almost 60% of the solids in black tea infusion remain uncharacterized. These compounds include the so-called thearubigins, which are a heterogeneous mixture of uncharacterized catechin oxidation products with oligomeric structures. This review summarizes the current knowledge of the production mechanisms of representative black tea polyphenols and presents recent progress in characterization of thearubigins.

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Section: 3 Production and Degradation Of Theaflavinsmentioning

confidence: 99%

Production Mechanisms of Black Tea Polyphenols

Tanaka

Matsuo

2020

Chem. Pharm. Bull.

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“…We identified natural product purpurogallin 9aa (Figure 2), isolated from nutgalls and oak bark, as an inhibitor of JmjC domain-containing KDMs (Kooistra and Helin, 2012;Berry and Janknecht, 2013;Black et al, 2013). This compound belongs to the family of benzotropolone-containing natural products (Nierenstein and Swanton, 1944; Barltrop and Nicholson, 1948;Arpin et al, 1974;Klostermeyer et al, 2000;Kerschensteiner et al, 2011;Matsuo et al, 2017) and was already known to display antioxidant (Wu et al, 1996) and anticancer activities (Kitada et al, 2003;Leone et al, 2003), and to play a role in the modulation of inflammatory responses (Sang et al, 2004). Purpurogallin and its synthetic analogs were more recently reported to function as inhibitors of Toll-like receptors 1/2 (Cheng et al, 2012), and to modulate mitogen-activated protein kinase 1/2 signaling pathway, reducing esophageal squamous cell carcinoma growth (Xie et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

A New Family of Jumonji C Domain-Containing KDM Inhibitors Inspired by Natural Product Purpurogallin

et al. 2020

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Aberrant epigenetic modifications are involved in cancer development. Jumonji C domain-containing histone lysine demethylases (KDMs) are found mainly up-regulated in breast, prostate, and colon cancer. Currently, growing interest is focusing on the identification and development of new inhibitors able to block the activity of KDMs and thus reduce tumor progression. KDM4A is known to play a role in several cellular physiological processes, and was recently found overexpressed in a number of pathological states, including cancer. In this work, starting from the structure of purpurogallin 9aa, previously identified as a natural KDM4A inhibitor, we synthesized two main sets of compound derivatives in order to improve their inhibitory activity against KDM4A in vitro and in cells, as well as their antitumor action. Based on the hypothetical biogenesis of the 5-oxo-5H-benzo[7]annulene skeleton of the natural product purpurogallin (Salfeld, 1960; Horner et al., 1961; Dürckheimer and Paulus, 1985; Tanaka et al., 2002; Yanase et al., 2005) the pyrogallol and catechol units were first combined with structural modifications at different positions of the aryl ring using enzyme-mediated oxidative conditions, generating a series of benzotropolone analogs. Two of the synthetic analogs of purpurogallin, 9ac and 9bc, showed an efficient inhibition (50 and 80%) of KDM4A in enzymatic assays and in cells by increasing levels of its specific targets, H3K9me3/2 and H3K36me3. However, these two compounds/derivatives did not induce cell death. We then synthesized a further set of analogs of these two compounds with greater structural diversification. The most potent of these analogs, 9bf, displayed the highest KDM4A inhibitory enzymatic activity in vitro (IC 50 of 10.1 and 24.37 µM) in colon cancer cells, and the strongest antitumor action in several solid and hematological human cancer cell lines with no toxic effect in normal cells. Our findings suggest that further development of this compound and its derivatives may lead to the identification of new therapeutic antitumor agents acting through inhibition of KDM4A.

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“…In 2017, Matsuo et al 91 pointed out that the proposed 1,2,3,4-naphthalenetetraol architecture was unknown in natural products and that the structure of goupiolone B could be in error. These authors also argued that the 13 C NMR chemical shifts for C-β in the α,β-unsaturated carbonyl moiety and in the 1,2,3,4-tetrahydroxynaphtalene were inappropriate for such systems.…”

Section: Goupiolone Bmentioning

confidence: 99%

“…These authors also argued that the 13 C NMR chemical shifts for C-β in the α,β-unsaturated carbonyl moiety and in the 1,2,3,4-tetrahydroxynaphtalene were inappropriate for such systems. Furthermore, Matsuo et al 91 speculated that goupiolone B should present structure 206 as it may be biosynthetically derived from goupiolone A after its coupling with catechol quinone 208 (see Scheme 30), followed by reduction.…”

Section: Goupiolone Bmentioning

confidence: 99%

Computer-Guided Total Synthesis of Natural Products. Recent Examples and Future Perspectives

Della‐Felice¹,

Pilli²,

Sarotti³

2018

J. Braz. Chem. Soc.

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Quantum chemical calculations of nuclear magnetic resonance (NMR) shifts and coupling constants have been extensively employed in recent years mainly to facilitate structural elucidation of organic molecules. When the results of such calculations are used to determine the most likely structure of a natural product in advance, guiding the subsequent synthetic work, the term "computer-guided synthesis" could be coined. This review article describes the most relevant examples from recent literature, highlighting the scope and limitations of this merged computational/experimental approach as well.

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Structural Revision and Biomimetic Synthesis of Goupiolone B

Cited by 15 publications

References 34 publications

Production Mechanisms of Black Tea Polyphenols

Production Mechanisms of Black Tea Polyphenols

A New Family of Jumonji C Domain-Containing KDM Inhibitors Inspired by Natural Product Purpurogallin

Computer-Guided Total Synthesis of Natural Products. Recent Examples and Future Perspectives

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