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Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

In the recent past, the design and synthesis of peptide mimics (peptidomimetics) has received much attention. This because they have shown in many cases enhanced pharmacological properties over their natural peptide analogues. In particular, the incorporation of cyclic constructs into peptides is of...

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Autores principales: Koopmanschap, Gijs, Ruijter, Eelco, Orru, Romano VA
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943360/
https://www.ncbi.nlm.nih.gov/pubmed/24605172
http://dx.doi.org/10.3762/bjoc.10.50
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author Koopmanschap, Gijs
Ruijter, Eelco
Orru, Romano VA
author_facet Koopmanschap, Gijs
Ruijter, Eelco
Orru, Romano VA
author_sort Koopmanschap, Gijs
collection PubMed
description In the recent past, the design and synthesis of peptide mimics (peptidomimetics) has received much attention. This because they have shown in many cases enhanced pharmacological properties over their natural peptide analogues. In particular, the incorporation of cyclic constructs into peptides is of high interest as they reduce the flexibility of the peptide enhancing often affinity for a certain receptor. Moreover, these cyclic mimics force the molecule into a well-defined secondary structure. Constraint structural and conformational features are often found in biological active peptides. For the synthesis of cyclic constrained peptidomimetics usually a sequence of multiple reactions has been applied, which makes it difficult to easily introduce structural diversity necessary for fine tuning the biological activity. A promising approach to tackle this problem is the use of multicomponent reactions (MCRs), because they can introduce both structural diversity and molecular complexity in only one step. Among the MCRs, the isocyanide-based multicomponent reactions (IMCRs) are most relevant for the synthesis of peptidomimetics because they provide peptide-like products. However, these IMCRs usually give linear products and in order to obtain cyclic constrained peptidomimetics, the acyclic products have to be cyclized via additional cyclization strategies. This is possible via incorporation of bifunctional substrates into the initial IMCR. Examples of such bifunctional groups are N-protected amino acids, convertible isocyanides or MCR-components that bear an additional alkene, alkyne or azide moiety and can be cyclized via either a deprotection–cyclization strategy, a ring-closing metathesis, a 1,3-dipolar cycloaddition or even via a sequence of multiple multicomponent reactions. The sequential IMCR-cyclization reactions can afford small cyclic peptide mimics (ranging from four- to seven-membered rings), medium-sized cyclic constructs or peptidic macrocycles (>12 membered rings). This review describes the developments since 2002 of IMCRs-cyclization strategies towards a wide variety of small cyclic mimics, medium sized cyclic constructs and macrocyclic peptidomimetics.
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spelling pubmed-39433602014-03-06 Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics Koopmanschap, Gijs Ruijter, Eelco Orru, Romano VA Beilstein J Org Chem Review In the recent past, the design and synthesis of peptide mimics (peptidomimetics) has received much attention. This because they have shown in many cases enhanced pharmacological properties over their natural peptide analogues. In particular, the incorporation of cyclic constructs into peptides is of high interest as they reduce the flexibility of the peptide enhancing often affinity for a certain receptor. Moreover, these cyclic mimics force the molecule into a well-defined secondary structure. Constraint structural and conformational features are often found in biological active peptides. For the synthesis of cyclic constrained peptidomimetics usually a sequence of multiple reactions has been applied, which makes it difficult to easily introduce structural diversity necessary for fine tuning the biological activity. A promising approach to tackle this problem is the use of multicomponent reactions (MCRs), because they can introduce both structural diversity and molecular complexity in only one step. Among the MCRs, the isocyanide-based multicomponent reactions (IMCRs) are most relevant for the synthesis of peptidomimetics because they provide peptide-like products. However, these IMCRs usually give linear products and in order to obtain cyclic constrained peptidomimetics, the acyclic products have to be cyclized via additional cyclization strategies. This is possible via incorporation of bifunctional substrates into the initial IMCR. Examples of such bifunctional groups are N-protected amino acids, convertible isocyanides or MCR-components that bear an additional alkene, alkyne or azide moiety and can be cyclized via either a deprotection–cyclization strategy, a ring-closing metathesis, a 1,3-dipolar cycloaddition or even via a sequence of multiple multicomponent reactions. The sequential IMCR-cyclization reactions can afford small cyclic peptide mimics (ranging from four- to seven-membered rings), medium-sized cyclic constructs or peptidic macrocycles (>12 membered rings). This review describes the developments since 2002 of IMCRs-cyclization strategies towards a wide variety of small cyclic mimics, medium sized cyclic constructs and macrocyclic peptidomimetics. Beilstein-Institut 2014-03-04 /pmc/articles/PMC3943360/ /pubmed/24605172 http://dx.doi.org/10.3762/bjoc.10.50 Text en Copyright © 2014, Koopmanschap et al. https://creativecommons.org/licenses/by/2.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms)
spellingShingle Review
Koopmanschap, Gijs
Ruijter, Eelco
Orru, Romano VA
Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
title Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
title_full Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
title_fullStr Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
title_full_unstemmed Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
title_short Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
title_sort isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3943360/
https://www.ncbi.nlm.nih.gov/pubmed/24605172
http://dx.doi.org/10.3762/bjoc.10.50
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