The Evolution of the Total Synthesis of Rocaglamide

Zhou, Zhe; Dixon, Darryl D.; Jolit, Anaïs; Tius, Marcus A.

doi:10.1002/chem.201603312

Cited by 28 publications

(15 citation statements)

References 78 publications

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“…The synthesis of fluoro derivative 5 is summarized in Scheme4.S ite-selective deprotonation of 12 [33] and subsequent condensation with acid chloride 13 furnished chalcone 14 a in 49 %y ield, and this was followed by derivatization to 2hydroxychalcone 14 b by site-selective cleavage of the methyl ether with boron tribromide to afford 14 b in 96 %y ield. A Scheme2.Designed derivatives 6-8,based on 4.T heir commonhydroxy group at C-7 was capped with mono-, di-and triglycosides instead oft he methylether in 4. combination of I 2 and pyridine [32] for the oxidative cyclization of the 2-hydroxychalcone furnished flavone 5 in quantitative yield.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 5‐Hydroxy‐3′,4′,7‐trimethoxyflavone and Related Compounds and Elucidation of Their Reversal Effects on BCRP/ABCG2‐Mediated Anticancer Drug Resistance

et al. 2018

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3',4',7-Trimethoxyflavone (TMF) has been reported to show a potent reversal effect on drug resistance mediated by breast cancer resistance protein (BCRP)/ATP-binding cassette subfamily G member 2 (ABCG2). In this study, we designed and synthesized five derivatives with either a hydroxy group or a fluorine atom at C-5 and several kinds of capping moiety at the C-7 hydroxy group, on the same 3',4'-dimethoxy-substituted flavone skeleton. We subsequently evaluated the efficacies of these compounds against BCRP-expressing human leukaemia K562/BCRP cells. Reversal of drug resistance was expressed as the concentration of compound causing a twofold reduction in drug sensitivity (RI ). Of the synthesized compounds, the reversal effect of 5-hydroxy-3',4',7-trimethoxyflavone (HTMF, RI 7.2 nm) towards 7-ethyl-10-hydroxycamptothecin (SN-38) was stronger than that of TMF (RI 18 nm). Fluoro-substituted 5-fluoro-3',4',7-trimethoxyflavone (FTMF, RI 25 nm) and monoglycosylated 7-(β-glucosyloxy)-5-hydroxy-3',4'-dimethoxyflavone (GOHDMF, 91 nm) also exhibited reversal effects, whereas the di- and triglycoside derivatives did not. TMF, HTMF and FTMF at 0.01-10 μm upregulated the K562/BCRP cellular accumulation of Hoechst 33342 nuclear staining dye. In addition, western blotting revealed that treatment of K562/BCRP cells with 0.1 μm TMF, HTMF or FTMT suppressed the expression of BCRP. HTMF showed the strongest inhibition of BCRP-mediated efflux and suppression of BCRP expression of the three effective synthesized flavones.

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Section: Resultsmentioning

confidence: 99%

Synthesis of 5‐Hydroxy‐3′,4′,7‐trimethoxyflavone and Related Compounds and Elucidation of Their Reversal Effects on BCRP/ABCG2‐Mediated Anticancer Drug Resistance

et al. 2018

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“…The discovery of cytotoxic activity of rocaglates, and their complex tricyclic framework, spurred significant interest in their synthesis, which has greatly enabled their therapeutic development. − Recently, Chu et al undertook a medicinal chemistry campaign that led to the identification of potent synthetic RocA derivative CR-1–31-B ( 9 ) (IC 50 = 9 nM in NIH/3T3 cells) (Figure ). , Key SAR findings were the addition of an electron-rich hydroxamate, which forms a hydrogen bonding interaction with Glu195 in eIF4A.…”

Section: Inhibition Of Eukaryotic Protein Translationmentioning

confidence: 99%

Inhibitors of Eukaryotic Translational Machinery as Therapeutic Agents

Fan

Sharp

2021

J. Med. Chem.

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Inhibiting eukaryotic protein translation with small molecules is emerging as a powerful therapeutic strategy. The advantage of targeting cellular translational machinery is that it is required for the highly proliferative state of many neoplastic cells, replication of certain viruses, and ultimately the expression of a wide variety of protein targets. Although, this approach has been exploited to develop clinical agents, such as homoharringtonine (HHT, 1), used to treat chronic myeloid leukemia (CML), inhibiting components of the translational machinery is often associated with cytotoxic phenotypes. However, recent studies have demonstrated that certain small molecules can inhibit the translation of specific subsets of proteins, leading to lower cytotoxicity, and opening-up therapeutic opportunities for translation inhibitors to be deployed in indications beyond oncology and infectious disease. This review summarizes efforts to develop inhibitors of the eukaryotic translational machinery as therapeutic agents and highlights emerging opportunities for translation inhibitors in the future.

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“…It is also worth noting that a majority of these syntheses are devoted to the diphenyl dihydrobenzofuran moiety found in the rocaglates. 21 , 23 , 24 , 34 , 39 − 51 …”

Section: Introductionmentioning

confidence: 99%

Synthesis of cis-Oriented Vicinal Diphenylethylenes through a Lewis Acid-Promoted Annulation of Oxotriphenylhexanoates

et al. 2021

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This study explores the synthesis of cyclic cis -vicinal phenyl ethylenes from oxotriphenylhexanoates. The reaction is a BBr 3 -promoted cyclization of 1,6-ketoesters ( 1 ) to five-membered diketo compounds ( 2 ). The synthesis is interesting as it constitutes one of the few examples of modular stereoselective synthesis of structures with a cis -oriented vicinal diphenylethylene. The core structure of 2 can be smoothly derivatized, which makes it a promising synthetic building block for further stereoselective synthetic applications.

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The Evolution of the Total Synthesis of Rocaglamide

Cited by 28 publications

References 78 publications

Synthesis of 5‐Hydroxy‐3′,4′,7‐trimethoxyflavone and Related Compounds and Elucidation of Their Reversal Effects on BCRP/ABCG2‐Mediated Anticancer Drug Resistance

Synthesis of 5‐Hydroxy‐3′,4′,7‐trimethoxyflavone and Related Compounds and Elucidation of Their Reversal Effects on BCRP/ABCG2‐Mediated Anticancer Drug Resistance

Inhibitors of Eukaryotic Translational Machinery as Therapeutic Agents

Synthesis of cis-Oriented Vicinal Diphenylethylenes through a Lewis Acid-Promoted Annulation of Oxotriphenylhexanoates

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