ArticleJournal of the American Chemical Society2010
An aldol-based build/couple/pair strategy for the synthesis of medium- and large-sized rings: discovery of macrocyclic histone deacetylase inhibitors.
Article in Journal of the American Chemical Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed.
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- High-Throughput Screens of Repurposing Hub and DOS Chemical Libraries Reveal Compounds with Novel and Potent Inhibitory Activity Against the Essential Non-Neuronal Acetylcholinesterase ofInternational journal of molecular sciences · 2025Article
- Large-scale combination screens reveal small-molecule sensitization of antibiotic-resistant gram-negative ESKAPE pathogens.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Massively parallel combination screen reveals small molecule sensitization of antibiotic-resistant Gram-negative ESKAPE pathogens.bioRxiv : the preprint server for biology · 2024Article
- Recent Progress on Synthesis of Functionalized 1,5-Disubstituted Triazoles.Current organic synthesis · 2024Review
- Diversity-oriented synthesis encoded by deoxyoligonucleotides.Nature communications · 2023Article
- Bis(oxiranes) Containing Cyclooctane Core: Synthesis and Reactivity towards NaNMolecules (Basel, Switzerland) · 2022Article
- Virtual screening for small-molecule pathway regulators by image-profile matching.Cell systems · 2022Article
- Redefining the Histone Deacetylase Inhibitor Pharmacophore: High Potency with No Zinc Cofactor Interaction.ACS medicinal chemistry letters · 2021Article
- Macrocycle synthesis strategy based on step-wise "adding and reacting" three components enables screening of large combinatorial libraries.Chemical science · 2020Article
- Chemical Inhibitors of a Selective SWI/SNF Function Synergize with ATR Inhibition in Cancer Cell Killing.ACS chemical biology · 2020Article
- A Domino 10-Step Total Synthesis of FR252921 and Its Analogues, Complex Macrocyclic Immunosuppressants.Journal of the American Chemical Society · 2019Article
- Thiol-to-amine cyclization reaction enables screening of large libraries of macrocyclic compounds and the generation of sub-kilodalton ligands.Science advances · 2019Article
- Chemical Space Overlap with Critical Protein-Protein Interface Residues in Commercial and Specialized Small-Molecule Libraries.ChemMedChem · 2019Article
- Synthesis of Benzannulated Medium-ring Lactams via a Tandem Oxidative Dearomatization-Ring Expansion Reaction.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- Chemical probes and drug leads from advances in synthetic planning and methodology.Nature reviews. Drug discovery · 2018Review
- Recent advances in the development of polycyclic skeletons via Ugi reaction cascades.Molecular diversity · 2018Review
- A Brief Overview of Two Major Strategies in Diversity-Oriented Synthesis: Build/Couple/Pair and Ring-Distortion.Frontiers in chemistry · 2018Review
- MacroEvoLution: A New Method for the Rapid Generation of Novel Scaffold-Diverse Macrocyclic Libraries.Chemistry (Weinheim an der Bergstrasse, Germany) · 2017Article
26 more citing papers are in PubMed but not listed here.
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Abstract
An aldol-based build/couple/pair (B/C/P) strategy was applied to generate a collection of stereochemically and skeletally diverse small molecules. In the build phase, a series of asymmetric syn- and anti-aldol reactions were performed to produce four stereoisomers of a Boc-protected γ-amino acid. In addition, both stereoisomers of O-PMB-protected alaninol were generated to provide a chiral amine coupling partner. In the couple step, eight stereoisomeric amides were synthesized by coupling the chiral acid and amine building blocks. The amides were subsequently reduced to generate the corresponding secondary amines. In the pair phase, three different reactions were employed to enable intramolecular ring-forming processes: nucleophilic aromatic substitution (S(N)Ar), Huisgen [3+2] cycloaddition, and ring-closing metathesis (RCM). Despite some stereochemical dependencies, the ring-forming reactions were optimized to proceed with good to excellent yields, providing a variety of skeletons ranging in size from 8- to 14-membered rings. Scaffolds resulting from the RCM pairing reaction were diversified on the solid phase to yield a 14 400-membered library of macrolactams. Screening of this library led to the discovery of a novel class of histone deacetylase inhibitors, which display mixed enzyme inhibition, and led to increased levels of acetylation in a primary mouse neuron culture. The development of stereo-structure/activity relationships was made possible by screening all 16 stereoisomers of the macrolactams produced through the aldol-based B/C/P strategy.
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