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Cyclic Peptidomimetics and Pseudopeptides from Multicomponent Reactions

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Synthesis of Heterocycles via Multicomponent Reactions I

Part of the book series: Topics in Heterocyclic Chemistry ((TOPICS,volume 23))

Abstract

Multicomponent reactions (MCRs) that provide in the final product amides are suitable to produce peptides and peptide-like moieties. The Passerini and Staudinger reactions provide one amide bond, and the Ugi-four-component reaction generates two amides from three or even four (or more) components, respectively. The Ugi-reaction thus is most important to produce peptides and peptoids while the Passerini reaction is useful to generate depsipeptoid moieties. In order to produce cyclic peptides and pseudopeptides, the linear peptidic MCR products have to be cyclized, usually with the help of bifunctional or activatable building blocks. Orthogonal but cyclizable secondary functionalities that need no protection in isonitrile MCRs commonly include alkenes (for ring closing metathesis), azide/alkyne (for Huisgen click reactions) or dienes and enoates (Diels-Alder) etc. If MCR-reactive groups are to be used also for the cyclisation, monoprotected bifunctional building blocks are used and deprotected after the MCR, e.g. for Ugi reactions as Ugi-Deprotection-Cyclisation (UDC). Alternatively one of the former building blocks or functional groups generated by the MCR can be activated. Most commonly these are activated amides (from so-called convertible isonitriles) which can be used e.g. for Ugi-Activation-Cyclisation (UAC) protocols, or most recently for a simultaneous use of both strategies Ugi-Deprotection/Activation-Cyclisation (UDAC). These methods mostly lead to small, medicinally relevant peptide turn mimics. In an opposing strategy, the MCR is rather used as ring-closing reaction, thereby introducing a (di-)peptide moiety. Most recently these processes have been combined to use MCRs for both, linear precursor synthesis and cyclisation. These multiple MCR approaches allow the most efficient and versatile one pot synthesis of macrocyclic pseudopeptides known to date.

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Authors and Affiliations

  1. Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120, Halle (Saale), Germany

    Ludger A. Wessjohann, Cristiano R. B. Rhoden, Daniel G. Rivera & Otilie Eichler Vercillo

  2. UNIFRA, Santa Maria, RS, Brasil

    Cristiano R. B. Rhoden

  3. University of Havana, Havana, Cuba

    Daniel G. Rivera

  4. University of Brasilia, Brasilia, Brasil

    Otilie Eichler Vercillo

Authors
  1. Ludger A. Wessjohann
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  2. Cristiano R. B. Rhoden
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  3. Daniel G. Rivera
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  4. Otilie Eichler Vercillo
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Correspondence to Ludger A. Wessjohann .

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  1. Fac. Sciences, Dept. Chemistry &, VU University Amsterdam, De Boelelaan 1083, Amsterdam, 1081 HV, Netherlands

    Romano V. A. Orru

  2. Faculty of Sciences, Section of Synthetic &, VU University Amsterdam, Amsterdam, 1081 HV, Netherlands

    Eelco Ruijter

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Wessjohann, L.A., Rhoden, C.R.B., Rivera, D.G., Vercillo, O.E. (2010). Cyclic Peptidomimetics and Pseudopeptides from Multicomponent Reactions. In: Orru, R., Ruijter, E. (eds) Synthesis of Heterocycles via Multicomponent Reactions I. Topics in Heterocyclic Chemistry, vol 23. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7081_2009_25

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