Formal Total Synthesis of Amphidinolide E

Bosch, Lluís; Mola, Laura; Petit, Elena; Saladrigas, Mar; Alonso‐Esteban, José Ignacio; Costa, Anna M.; Vilarrasa, Jaume

doi:10.1021/acs.joc.7b01973

Cited by 16 publications

(16 citation statements)

References 53 publications

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“…There are no metadynamics studies of other antimitotic macrolides, the total syntheses of which are a long-standing research line of the senior author. 41−45 There is only one metadynamics study that involves the microtubule-destabilizing agent combretastatin. 46 Two works on the energy profiles of other antimitotic agents have also been reported.…”

Section: Results and Discussionmentioning

confidence: 99%

Further Insight into the Interactions of the Cytotoxic Macrolides Laulimalide and Peloruside A with Their Common Binding Site

2018

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The binding site of the macrolides laulimalide and peloruside A, which is different from that of the clinically useful drugs paclitaxel/taxol and ixabepilone ( tax site ), is known to be between two adjacent β-tubulin units ( ext site ). Here, we report our study of the binding of these molecules to an α1β1/α2β2-tubulin “tetramer” model. AutoDock 4.2.6//AutoDock Vina dockings predicted that the affinities of laulimalide and peloruside A for the tax site are quite similar to those for the ext site . However, molecular dynamics (MD) simulations indicated that only when these two ligands are located at the ext site , there are contacts that help stabilize the system, favoring the β1/β2 interactions. The binding affinity of laulimalide for this site is stronger than that of peloruside A, but this is compensated for by additional β1/β2 contacts that are induced by peloruside A. MD studies also suggested that epothilones at the tax site and either laulimalide or peloruside A at the ext site cause similar stabilizing effects (mainly linking the M-loop of β1 and loop H1–B2 of β2). In a “hexamer” model (3 units of αβ-tubulin), the effects are confirmed. Metadynamics simulations of laulimalide and peloruside A, which are reported for the first time, suggest that peloruside A produces a stronger change in the M-loop, which explains the stabilization of the β1/β2 interaction.

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Section: Results and Discussionmentioning

confidence: 99%

Further Insight into the Interactions of the Cytotoxic Macrolides Laulimalide and Peloruside A with Their Common Binding Site

2018

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“…After the deprotection of the TBS group, the Mitsunobu reaction was applied to convert the compound 13 into tetrazole 15 in 94% yield. Then the SPT part was oxidized by H 2 O 2 (20 eq) in the presence of (NH 4 ) 6 Mo 7 O 24 (0.2 eq) to obtain the desired 2 without the Z isomer [ 12 ].…”

Section: Resultsmentioning

confidence: 99%

Asymmetric Synthesis of the C15–C32 Fragment of Alotamide and Determination of the Relative Stereochemistry

Shi

Xie

et al. 2018

Marine Drugs

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Alotamide is a cyclic depsipetide isolated from a marine cyanobacterium and possesses a unique activation of calcium influx in murine cerebrocortical neurons (EC50 4.18 µM). Due to its limited source, the three stereocenters (C19, C28, and C30) in its polyketide fragment remain undetermined. In this study, the first asymmetric synthesis of its polyketide fragment was achieved. Four relative possible diastereomers were constructed with a boron-mediated enantioselective aldol reaction and Julia–Kocienski olefination as the key steps. Comparison of 13C NMR spectra revealed the relative structure of fragment C15–C32 of alotamide.

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“…Recently, Vilarrasa and Costa presented a different approach to its total synthesis. Though no significant improvement was made in terms of yield or number of steps, this work provides interesting insights into Julia-Kocienski olefinations [25]. Thus, epoxidation of alcohol 11 directly afforded tetrahydrofuran 12, through a tandem epoxidation-cyclization reaction.…”

Section: Amphidinolidesmentioning

confidence: 94%

The Tetrahydrofuran Motif in Polyketide Marine Drugs

et al. 2022

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Oxygen heterocycles are units that are abundant in a great number of marine natural products. Among them, marine polyketides containing tetrahydrofuran rings have attracted great attention within the scientific community due to their challenging structures and promising biological activities. An overview of the most important marine tetrahydrofuran polyketides, with a focused discussion on their isolation, structure determination, approaches to their total synthesis, and biological studies is provided.

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Formal Total Synthesis of Amphidinolide E

Cited by 16 publications

References 53 publications

Further Insight into the Interactions of the Cytotoxic Macrolides Laulimalide and Peloruside A with Their Common Binding Site

Further Insight into the Interactions of the Cytotoxic Macrolides Laulimalide and Peloruside A with Their Common Binding Site

Asymmetric Synthesis of the C15–C32 Fragment of Alotamide and Determination of the Relative Stereochemistry

The Tetrahydrofuran Motif in Polyketide Marine Drugs

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