ArticleThe Journal of organic chemistry2011
Total syntheses of the histone deacetylase inhibitors largazole and 2-epi-largazole: application of N-heterocyclic carbene mediated acylations in complex molecule synthesis.
Article in The Journal of organic chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Marine Cyanobacteria as Sources of Lead Anticancer Compounds: A Review of Families of Metabolites with Cytotoxic, Antiproliferative, and Antineoplastic Effects.Molecules (Basel, Switzerland) · 2022Review
- Process Development and Scale-up Total Synthesis of Largazole, a Potent Class I Histone Deacetylase Inhibitor.Organic process research & development · 2018Article
- Synthesis and biological evaluation of largazole zinc-binding group analogs.Bioorganic & medicinal chemistry · 2017Article
- Largazole Analogues Embodying Radical Changes in the Depsipeptide Ring: Development of a More Selective and Highly Potent Analogue.Journal of medicinal chemistry · 2016Article
- Epigenetic modulators as therapeutic targets in prostate cancer.Clinical epigenetics · 2016Review
- Synthesis and biological evaluation of largazole analogues with modified surface recognition cap groups.European journal of medicinal chemistry · 2014Article
- Evaluation of class I HDAC isoform selectivity of largazole analogues.Bioorganic & medicinal chemistry letters · 2014Article
- Potent and orally efficacious bisthiazole-based histone deacetylase inhibitors.ACS medicinal chemistry letters · 2014Article
- Asymmetric NHC-catalyzed synthesis of α-fluoroamides from readily accessible α-fluoroenals.Chemical science · 2013Article
- A survey of marine natural compounds and their derivatives with anti-cancer activity reported in 2011.Molecules (Basel, Switzerland) · 2013Review
- Biological evaluation of new largazole analogues: alteration of macrocyclic scaffold with click chemistry.ACS medicinal chemistry letters · 2013Article
- Expanding the druggable space of the LSD1/CoREST epigenetic target: new potential binding regions for drug-like molecules, peptides, protein partners, and chromatin.PLoS computational biology · 2013Article
- A continuum of progress: applications of N-hetereocyclic carbene catalysis in total synthesis.Angewandte Chemie (International ed. in English) · 2012Review
- Discovery and mechanism of natural products as modulators of histone acetylation.Current drug targets · 2012Review
- Exploiting Acyl and Enol Azolium Intermediates via NHeterocyclic Carbene Catalyzed Reactions of Alpha-Reducible Aldehydes.Advanced synthesis & catalysis · 2012Article
- Largazole: from discovery to broad-spectrum therapy.Natural product reports · 2012Review
- Article
- A journey under the sea: the quest for marine anti-cancer alkaloids.Molecules (Basel, Switzerland) · 2011Review
- Largazole and analogues with modified metal-binding motifs targeting histone deacetylases: synthesis and biological evaluation.Journal of medicinal chemistry · 2011Article
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4 authors.
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Abstract
Details of the evolution of strategies toward convergent assembly of the histone deacetylase inhibiting natural product largazole exploiting γ,δ-unsaturated-α,β-epoxy-aldehydes and a thiazole-thiazoline containing ω-amino-acid are described. The initial N-heterocyclic carbene mediated redox amidation exploying these two types of building blocks representing largazole's structural domains of distinct biosynthetic origin directly afforded the seco-acid of largazole. This was accomplished without any protecting groups resident upon either thioester bearing epoxy-aldehyde or the tetrapeptide. However, the ineffective production of largazole via the final macrolactonization led to an alternative intramolecular esterification/macrolactamization strategy employing the established two building blocks. This provided largazole along with its C2-epimer via an unexpected inversion of the α-stereocenter at the valine residue. The biological evaluation demonstrated that both largazole and 2-epi-largazole led to dose-dependent increases of acetylation of histone H3, indicating their potencies as class I histone deacetylase selective inhibitiors. Enhanced p21 expression was also induced by largazole and its C2 epimer. In addition, 2-epi-largazole displayed more potent activity than largazole in cell viability assays against PC-3 and LNCaP prostate cancer cell lines.
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