Cyclic Peptidomimetics and Pseudopeptides from Multicomponent Reactions

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

“…However, as both the Ugi and Passerini reactions provide linear products, several cyclization strategies have been utilized in order to obtain cyclic constructs. For example, the incorporation of cyclic imines immediately gives cyclic MCR-products, whereas other strategies make use of unreactive, convertible or protected functional Ugi-substrates that can be cyclized via subsequent transformations [19,22,26]. Examples of IMCR orthogonal species or functionalities are alkenes, alkynes and azides which may give the cyclic analogues via subsequent ring closing metathesis (RCM) or 1,3-dipolar cycloadditions.…”

“…In addition, other MCR-post-condensation reactions, especially for macrocycles, include intramolecular aryl couplings, amidations, S n Ar reactions, nucleophilic substitutions, and macrolactonizations. Even more interestingly, it is possible to perform the cyclization step via a second multicomponent reaction [22] or the MiB ( m ultiple multicomponent macrocyclizations i ncluding b ifunctional building blocks) protocol developed by Wessjohann et al (vide infra) [26]. …”

Highly Stereoselective Synthesis of Natural‐Product‐Like Hybrids by an Organocatalytic/Multicomponent Reaction Sequence

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In an endeavor to providea ne fficient route to natural product hybrids,described herein is an efficient, highly stereoselective,one-pot process comprising an organocatalytic conjugate addition of 1,3-dicarbonyls to a,b-unsaturated aldehydes followed by an intramolecular isocyanide-based multicomponent reaction. [9] Moreover,t he intrinsic characteristics of I-MCRs may be further improved when they are combined with either pre- [10] or post-MCR [11] modifications.H owever, most efforts have been devoted to the latter one, [11,12] whereas examples describing pre-MCR modifications are quite seldom. The strategy combines the stereocontrol of organocatalysis with the diversity-generating character of multicomponent reactions,t hus leading to structurally unique peptidomimetics integrating heterocyclic,l ipidic, and sugar moieties.

The generation and decoration of privileged natural product scaffolds is as uccessful strategy for obtaining libraries of bioactive compounds.

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“…[9] Moreover,t he intrinsic characteristics of I-MCRs may be further improved when they are combined with either pre- [10] or post-MCR [11] modifications.H owever, most efforts have been devoted to the latter one, [11,12] whereas examples describing pre-MCR modifications are quite seldom. [9] Moreover,t he intrinsic characteristics of I-MCRs may be further improved when they are combined with either pre- [10] or post-MCR [11] modifications.H owever, most efforts have been devoted to the latter one, [11,12] whereas examples describing pre-MCR modifications are quite seldom.…”

“…[9] Moreover,t he intrinsic characteristics of I-MCRs may be further improved when they are combined with either pre- [10] or post-MCR [11] modifications.H owever, most efforts have been devoted to the latter one, [11,12] whereas examples describing pre-MCR modifications are quite seldom. [11,13] Aminocatalysis has been applied with great success in the a-, b-, gand even e-asymmetric functionalization of carbonyls. [11,13] Aminocatalysis has been applied with great success in the a-, b-, gand even e-asymmetric functionalization of carbonyls.…”