Synthesis of Chromeno[3,4-b]piperazines by an Enol-Ugi/Reduction/Cyclization Sequence

Keto piperazines and aminocoumarins are privileged building blocks for the construction of geometrically constrained peptides and therefore valuable structures in drug discovery. Combining these two heterocycles provides unique rigid polycyclic peptidomimetics with drug-like properties including many points of diversity that could be modulated to interact with different biological receptors. This work describes an efficient multicomponent approach to condensed chromenopiperazines based on the novel enol-Ugi reaction. Importantly, this strategy involves the first reported post-condensation transformation of an enol-Ugi adduct.

• Publication year

  2021

• Venue

  Molecules

• Publication date

  2021-02-27

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.3390/molecules26051287PMID 33673443PMCID 7956738
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Coumarin-piperazine derivatives as biologically active compounds

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  2017influential reference
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  2015cited by this paper
• Coumarin heterocyclic derivatives: chemical synthesis and biological activity.

  2015cited by this paper
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  2015cited by this paper
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  2014cited by this paper
• New aminocoumarin antibiotics as gyrase inhibitors.

  2014cited by this paper
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  2013cited by this paper
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  2013cited by this paper
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  2012cited by this paper
• Enols as feasible acid components in the Ugi condensation.

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• A new approach to construct a fused 2-ylidene chromene ring: highly regioselective synthesis of novel chromeno quinoxalines.

  2012influential reference
• The Piperazine Space in Isocyanide‐Based MCR Chemistry

  2011cited by this paper
• A multicomponent approach to the synthesis of 1,3-dicarbonylic compounds

  2011cited by this paper
• The Piperazine Space in Isocyanide-based MCR Chemistry

  2010cited by this paper
• Praziquantel and Schistosomiasis

  2010cited by this paper
• Mirtazapine

  2009cited by this paper
• Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules.

  2009cited by this paper
• Facile synthesis of structurally diverse 5-oxopiperazine-2-carboxylates as dipeptide mimics and templates.

  2009cited by this paper
• Ugi-Smiles Access to Quinoxaline Derivatives.

  2008cited by this paper
• Cannabilactones: a novel class of CB2 selective agonists with peripheral analgesic activity.

  2007cited by this paper
• Zinc catalysed ester solvolysis. Application to the synthesis of tartronic acid derivatives

  2006cited by this paper
• Synthesis of antimicrobial 2,9,10-trisubstituted-6-oxo-7,12-dihydro-chromeno[3,4-b]quinoxalines.

  2006cited by this paper
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  2005cited by this paper
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  2004cited by this paper
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  2003cited by this paper
• Solid-supported synthesis of putative peptide beta-turn mimetics via Ugi reaction for diketopiperazine formation.

  2002cited by this paper
• Design and synthesis of novel conformationally restricted peptide secondary structure mimetics

  2000cited by this paper
• Novel applications of convertible isonitriles for the synthesis of mono and bicyclic γ-lactams via a UDC strategy

  2000cited by this paper
• Solid-Supported Synthesis of a Peptide β-Turn Mimetic

  2000cited by this paper
• Solid-supported synthesis of a peptide beta-turn mimetic.

  2000cited by this paper
• An Easy Access to Bicyclic Peptides with an Octahydro[2H]pyrazino[1,2‐a]pyrazine Skeleton

  1999cited by this paper
• Design and synthesis of conformationally constrained amino acids as versatile scaffolds and peptide mimetics

  1997influential reference
• Naphthylisoquinoline alkaloids exhibit strong growth-inhibiting activities against Plasmodium falciparum and P. berghei in vitro--structure-activity relationships of dioncophylline C.

  1996cited by this paper
• Photophysical Properties of Pyrazinopsoralen, A New Monofunctional Psoralen *

  1996influential reference
• Peptidomimetics—Tailored Enzyme Inhibitors†

  1994cited by this paper
• Peptidomimetics for Receptor Ligands—Discovery, Development, and Medical Perspectives

  1993influential reference
• Investigations of pyrans and related compounds

  1973cited by this paper
• Mittheilungen aus dem Universitätslaboratorium in Pisa: Eine neue Reihe organischer Basen

  year unknowncited by this paper

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• Stefano Marcaccini: a pioneer in isocyanide chemistry

  2023cites this paper
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