Syntheses of Thailandepsin B Pseudo‐Natural Products: Access to New Highly Potent HDAC Inhibitors via Late‐Stage Modification

Brosowsky, Jana; Lutterbeck, Monika; Liebich, Amelie; Keller, Manfred; Herp, Daniel; Vogelmann, Anja; Jung, Manfred; Breit, Bernhard

doi:10.1002/chem.202002449

Cited by 11 publications

(11 citation statements)

References 43 publications

(36 reference statements)

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“…Most recently, Brosowsky et al [ 139 ] synthesized thailandepsin B pseudo-natural products with varying warheads. Compound 68 was identified as the most potent, inhibiting HDAC1 with 12.2 nM.…”

Section: Thiol Warheadsmentioning

confidence: 99%

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Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Frühauf

Meyer‐Almes

2021

Molecules

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Histone deacetylases (HDACs) remove acetyl groups from acetylated lysine residues and have a large variety of substrates and interaction partners. Therefore, it is not surprising that HDACs are involved in many diseases. Most inhibitors of zinc-dependent HDACs (HDACis) including approved drugs contain a hydroxamate as a zinc-binding group (ZBG), which is by far the biggest contributor to affinity, while chemical variation of the residual molecule is exploited to create more or less selectivity against HDAC isozymes or other metalloproteins. Hydroxamates have a propensity for nonspecificity and have recently come under considerable suspicion because of potential mutagenicity. Therefore, there are significant concerns when applying hydroxamate-containing compounds as therapeutics in chronic diseases beyond oncology due to unwanted toxic side effects. In the last years, several alternative ZBGs have been developed, which can replace the critical hydroxamate group in HDACis, while preserving high potency. Moreover, these compounds can be developed into highly selective inhibitors. This review aims at providing an overview of the progress in the field of non-hydroxamic HDACis in the time period from 2015 to present. Formally, ZBGs are clustered according to their binding mode and structural similarity to provide qualitative assessments and predictions based on available structural information.

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Section: Thiol Warheadsmentioning

confidence: 99%

“…Selected sulfur-containing compounds depicted as prodrugs or in their active thiol form. Chelating atoms and IC 50 values below 1 µM are highlighted in red.Most recently, Brosowsky et al[139] synthesized thailandepsin B pseudo-natural products with varying warheads. Compound 68 was identified as the most potent, inhibiting HDAC1 with 12.2 nM.…”

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confidence: 99%

Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Frühauf

Meyer‐Almes

2021

Molecules

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“…[13] Verbindung 13 ist ein selektiver Hemmer der Histon-Deacetylase HDAC1 und Gegenstand aktueller medizinisch-chemischer Entwicklungsarbeiten. [14] Im Gegensatz zum eher seltenen Vorkommen in Naturstoffen wird Norleucin 4 in der Entwicklung von therapeutischen Peptiden und Peptidomimetika gerne als stabilisierender Methionin-Ersatz verwendet. SCH 900518 (Narlaprevir) 15 (Abb.…”

Section: Columnsunclassified

Die bedeutende nicht-proteinogene Aminosäure Norleucin und ihre komplizierte Namensfindung

Vock

2021

Chimia

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“…Notably, the method is tolerant of free alcohols and could be used to form a quaternary stereocenter with excellent enantioselectivity. Additionally, the Breit group has shown the robustness of this method with the formation of various macrocyclic scaffolds, as well as key intermediates en route to several natural products. − …”

Section: Transition Metal Catalysismentioning

confidence: 99%

Catalytic Asymmetric Hydroalkoxylation of C–C Multiple Bonds

et al. 2021

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Asymmetric hydroalkoxylation of alkenes constitutes a redox-neutral and 100% atom-economical strategy toward enantioenriched oxygenated building blocks from readily available starting materials. Despite their great potential, catalytic enantioselective additions of alcohols across a C–C multiple bond are particularly underdeveloped, especially compared to other hydrofunctionalization methods such as hydroamination. However, driven by some recent innovations, e.g., asymmetric MHAT methods, asymmetric photocatalytic methods, and the development of extremely strong chiral Brønsted acids, there has been a gratifying surge of reports in this burgeoning field. The goal of this review is to survey the growing landscape of asymmetric hydroalkoxylation by highlighting exciting new advances, deconstructing mechanistic underpinnings, and drawing insight from related asymmetric hydroacyloxylation and hydration. A deep appreciation of the underlying principles informs an understanding of the various selectivity parameters and activation modes in the realm of asymmetric alkene hydrofunctionalization while simultaneously evoking the outstanding challenges to the field moving forward. Overall, we aim to lay a foundation for cross-fertilization among various catalytic fields and spur further innovation in asymmetric hydroalkoxylations of C–C multiple bonds.

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Syntheses of Thailandepsin B Pseudo‐Natural Products: Access to New Highly Potent HDAC Inhibitors via Late‐Stage Modification

Cited by 11 publications

References 43 publications

Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Die bedeutende nicht-proteinogene Aminosäure Norleucin und ihre komplizierte Namensfindung

Catalytic Asymmetric Hydroalkoxylation of C–C Multiple Bonds

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