Total Synthesis of Peloruside A through Kinetic Lactonization and Relay Ring‐Closing Metathesis Cyclization Reactions

Hoye, Thomas R.; Jeon, Junha; Kopel, Lucas C.; Ryba, Troy D.; Tennakoon, Manomi A.; Wang, Yini

doi:10.1002/anie.201002293

Cited by 54 publications

(5 citation statements)

References 44 publications

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“…The first total synthesis of peloruside A was reported in 2003 by De Brandander and co-workers . Several other approaches to this natural product were later developed. − In addition to 38 , other naturally occurring congeners have been isolated, , including peloruside B ( 39 , Figure ), which exhibits similar MT-stabilizing and biological activities as 38 …”

Section: Mt-stabilizing Natural Products and Analogues Thereofmentioning

confidence: 99%

Microtubule Stabilizing Agents as Potential Treatment for Alzheimer’s Disease and Related Neurodegenerative Tauopathies

et al. 2012

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The microtubule (MT)-associated protein tau, which is highly expressed in the axons of neurons, is an endogenous MT-stabilizing agent that plays an important role in the axonal transport. Loss of MT-stabilizing tau function, caused by misfolding, hyperphosphorylation and sequestration of tau into insoluble aggregates, leads to axonal transport deficits with neuropathological consequences. Several in vitro and preclinical in vivo studies have shown that MT-stabilizing drugs can be utilized to compensate for the loss of tau function and to maintain/restore an effective axonal transport. These findings indicate that MT-stabilizing compounds hold considerable promise for the treatment of Alzheimer disease and related tauopathies. The present article provides a synopsis of the key findings demonstrating the therapeutic potential of MT-stabilizing drugs in the context of neurodegenerative tauopathies, as well as an overview of the different classes of MT-stabilizing compounds.

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Section: Mt-stabilizing Natural Products and Analogues Thereofmentioning

confidence: 99%

Microtubule Stabilizing Agents as Potential Treatment for Alzheimer’s Disease and Related Neurodegenerative Tauopathies

et al. 2012

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“…That is why, similarly to other aforementioned compounds, novel ways of their industrial production are being sought. Up to now, six total syntheses of compound 12a have been reported [ 114 , 115 , 116 , 117 , 118 , 119 ]. At the same time, twenty novel derivatives, arisen either by total synthesis or semisynthetic approaches, have been presented, summarized in Brackovic et al (2015) [ 120 ].…”

Section: Microtubule Inhibitorsmentioning

confidence: 99%

Mitotic Poisons in Research and Medicine

et al. 2020

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Cancer is one of the greatest challenges of the modern medicine. Although much effort has been made in the development of novel cancer therapeutics, it still remains one of the most common causes of human death in the world, mainly in low and middle-income countries. According to the World Health Organization (WHO), cancer treatment services are not available in more then 70% of low-income countries (90% of high-income countries have them available), and also approximately 70% of cancer deaths are reported in low-income countries. Various approaches on how to combat cancer diseases have since been described, targeting cell division being among them. The so-called mitotic poisons are one of the cornerstones in cancer therapies. The idea that cancer cells usually divide almost uncontrolled and far more rapidly than normal cells have led us to think about such compounds that would take advantage of this difference and target the division of such cells. Many groups of such compounds with different modes of action have been reported so far. In this review article, the main approaches on how to target cancer cell mitosis are described, involving microtubule inhibition, targeting aurora and polo-like kinases and kinesins inhibition. The main representatives of all groups of compounds are discussed and attention has also been paid to the presence and future of the clinical use of these compounds as well as their novel derivatives, reviewing the finished and ongoing clinical trials.

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“…37 40 Five other total syntheses have been reported. [41][42][43][44][45] Unfortunately, current synthetic methods for ether generation lack the selectivity of evolved proteins. Thus, discrete steps for generating a hydroxyl stereogenic center and subsequent methylation are typically bracketed by additional protecting group manipulation steps.…”

Section: Formation Of 13-diols From Homoallylic Alcohol Derivativesmentioning

confidence: 99%

Ether Transfer Methodology: Application to the Synthesis of Polyketide Natural Products

Stefan

Taylor

2013

Stereoselective Synthesis of Drugs and Natural Products

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This chapter comprises two major components that sequentially describe existing methods pertinent to the stereoselective formation of 1,3‐ syn ‐diol functionality and the development of a new approach to 1,3‐ syn ‐diol monoethers and diethers through electrophilic activation of homoallylic alkoxymethyl ethers. The ability to quench a key chloromethyl ether intermediate with various nucleophiles highlights the versatility of the ether transfer method. The process provides selective access to either diol‐monoethers or diethers, and it describes an opportunity to convert acyclic stereochemically rich fragments into highly functionalized pyran systems. This fundamentally new method was successfully applied to the synthesis of several complex polyketides including the synthesis of isotactic polyethers, the C7–C17 fragment of swinholide A, the C3–C17 fragment of phorboxazole A, and the neopeltolide macrolactone.

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Total Synthesis of Peloruside A through Kinetic Lactonization and Relay Ring‐Closing Metathesis Cyclization Reactions

Cited by 54 publications

References 44 publications

Microtubule Stabilizing Agents as Potential Treatment for Alzheimer’s Disease and Related Neurodegenerative Tauopathies

Microtubule Stabilizing Agents as Potential Treatment for Alzheimer’s Disease and Related Neurodegenerative Tauopathies

Mitotic Poisons in Research and Medicine

Ether Transfer Methodology: Application to the Synthesis of Polyketide Natural Products

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