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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Beilstein-Institut
2014-03-01
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| Series: | Beilstein Journal of Organic Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.3762/bjoc.10.50 |
| _version_ | 1818577645955186688 |
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| author | Gijs Koopmanschap Eelco Ruijter Romano V.A. Orru |
| author_facet | Gijs Koopmanschap Eelco Ruijter Romano V.A. Orru |
| author_sort | Gijs Koopmanschap |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-16T06:33:13Z |
| format | Article |
| id | doaj.art-87c5e7cdf9d243d7a7c9a2fadb4e2395 |
| institution | Directory Open Access Journal |
| issn | 1860-5397 |
| language | English |
| last_indexed | 2024-12-16T06:33:13Z |
| publishDate | 2014-03-01 |
| publisher | Beilstein-Institut |
| record_format | Article |
| series | Beilstein Journal of Organic Chemistry |
| spelling | doaj.art-87c5e7cdf9d243d7a7c9a2fadb4e23952022-12-21T22:40:51ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972014-03-0110154459810.3762/bjoc.10.501860-5397-10-50Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimeticsGijs Koopmanschap0Eelco Ruijter1Romano V.A. Orru2Department of Chemistry & Pharmaceutical Sciences, Amsterdam Institute of Molecules, Medicines and Systems, VU University Amsterdam, de Boelelaan 1083, 1081 HV, Amsterdam, The NetherlandsDepartment of Chemistry & Pharmaceutical Sciences, Amsterdam Institute of Molecules, Medicines and Systems, VU University Amsterdam, de Boelelaan 1083, 1081 HV, Amsterdam, The NetherlandsDepartment of Chemistry & Pharmaceutical Sciences, Amsterdam Institute of Molecules, Medicines and Systems, VU University Amsterdam, de Boelelaan 1083, 1081 HV, Amsterdam, The NetherlandsIn 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.https://doi.org/10.3762/bjoc.10.50heterocyclesisocyanidesmacrocyclesmulticomponent reactionmedicinal chemistryorganic synthesispeptidomimetics |
| spellingShingle | Gijs Koopmanschap Eelco Ruijter Romano V.A. Orru Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics Beilstein Journal of Organic Chemistry heterocycles isocyanides macrocycles multicomponent reaction medicinal chemistry organic synthesis 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 | heterocycles isocyanides macrocycles multicomponent reaction medicinal chemistry organic synthesis peptidomimetics |
| url | https://doi.org/10.3762/bjoc.10.50 |
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