Application of Olefin Cross-Metathesis to the Synthesis of Biologically Active Natural Products

Prunet, Joëlle

doi:10.2174/156802605775009801

Cited by 39 publications

(8 citation statements)

References 58 publications

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“… 19 Reaction of the resulting alcohol with acrolein diethyl acetal in the presence of a catalytic amount of PPTS in benzene at 23 °C for 12 h afforded ethyl acetal 10 as a mixture (1:1 by 1 H NMR) of diastereomers in 74% yield. This mixture was subjected to ring-closing metathesis using Grubbs’ second-generation catalyst 20 , 21 in the presence of NaHCO 3 in CH 2 Cl 2 at reflux. This condition resulted in a 1:1 mixture of dihydropyran derivative in 86% yield.…”

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confidence: 99%

Enantioselective Synthesis of Spliceostatin E and Evaluation of Biological Activity

et al. 2014

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An enantioselective total synthesis of spliceostatin E has been accomplished. The δ-lactone unit A was constructed from readily available (R)-glycidyl alcohol using a ring-closing olefin metathesis as the key reaction. A cross-metathesis of ring A containing δ-lactone and the functionalized tetrahydropyran B-ring provided spliceostatin E. Our biological evaluation of synthetic spliceostatin E revealed that it does not inhibit splicing in vitro and does not impact speckle morphology in cells. Spliceostatin E was reported to possess potent antitumor activity.

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confidence: 99%

Enantioselective Synthesis of Spliceostatin E and Evaluation of Biological Activity

et al. 2014

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“…As shown in Scheme 1, we planned to utilize cross-metathesis 7 to couple the epoxy alcohol segment 3 and the amide segment 4 at a late stage of the synthesis. A related strategy was utilized by Koide and co-workers.…”

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Enantioselective Syntheses of FR901464 and Spliceostatin A: Potent Inhibitors of Spliceosome

Ghosh

Chen

2013

Org. Lett.

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Enantioselective syntheses of FR901464 and Spliceostatin A, potent spliceosome inhibitors are described. The synthesis of FR901464 has been accomplished in a convergent manner in 10 linear steps (20 total steps). The synthesis of the A-tetrahydropyran ring was constructed from (R)-isopropylidene glyceraldehyde. The functionalized tetrahydropyran B-ring was synthesized utilizing a Corey-Bakshi-Shibata reduction, an Achmatowicz reaction, and a stereoselective Michael addition as the key steps. Coupling of A- and B-ring fragments was accomplished via cross-metathesis.

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“…Optically active epoxide 143 was opened with isopropenylmagnesium bromide in the presence of 10 mol % CuCN, and the resulting alcohol was subjected to etherification to afford acetal 144 . Ring-closing metathesis in the presence of 10 mol % Grubb’s second-generation catalyst furnished cyclic ethers 145 and 146 as a 1:1 diastereomeric ratio. , Camphorsulfonic acid (CSA)-induced racemization resulted in diastereomer 145 as the major isomer in 93% yield. Dihydropyran 145 was then converted to alkene derivative 147 in a three-step sequence.…”

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confidence: 99%

Spliceostatins and Derivatives: Chemical Syntheses and Biological Properties of Potent Splicing Inhibitors

2021

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Spliceostatins and thailanstatins are intriguing natural products due to their structural features as well as their biological significance. This family of natural products has been the subject of immense synthetic interest because they exhibit very potent cytotoxicity in representative human cancer cell lines. The cytotoxic properties of these natural products are related to their ability to inhibit spliceosomes. FR901564 and spliceostatins have been shown to inhibit spliceosomes by binding to their SF3B component. Structurally, these natural products contain two highly functionalized tetrahydropyran rings with multiple stereogenic centers joined by a diene moiety and an acyclic side chain linked with an amide bond. Total syntheses of this family of natural products led to the development of useful synthetic strategies, which enabled the synthesis of potent derivatives. The spliceosome modulating properties of spliceostatins and synthetic derivatives opened the door for understanding the underlying spliceosome mechanism as well as the development of new therapies based upon small-molecule splicing modulators. This review outlines the total synthesis of spliceostatins, synthetic studies of structural derivatives, and their bioactivity.

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Application of Olefin Cross-Metathesis to the Synthesis of Biologically Active Natural Products

Cited by 39 publications

References 58 publications

Enantioselective Synthesis of Spliceostatin E and Evaluation of Biological Activity

Enantioselective Synthesis of Spliceostatin E and Evaluation of Biological Activity

Enantioselective Syntheses of FR901464 and Spliceostatin A: Potent Inhibitors of Spliceosome

Spliceostatins and Derivatives: Chemical Syntheses and Biological Properties of Potent Splicing Inhibitors

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