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

Echemendía, Radell; Torre, Alexander F. de la; Monteiro, Julia L.; Pila, Michel; Corrêa, Arlene G.; Westermann, Bernhard; Rivera, Daniel G.; Paixão, Márcio W.

doi:10.1002/ange.201412074

Cited by 13 publications

(3 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…164 As depicted in Scheme 22, the authors employed an initial asymmetric conjugate addition of 3-phenyl-3-oxo-propanenitrile to cinnamaldehyde catalyzed by diarylprolinol silyl ether to furnish a chiral hemiacetal bearing an aldehyde and an enol functionality. This enantiomerically enriched bifunctional intermediate was employed in an isocyanide-based MCR recently developed in cooperation between the two laboratories 165 which encompasses the diastereoselective condensation of the bifunctional substrate with an amine and an isocyanide, in this case both of peptidic nature. Thus, the use of a isocyano-tripeptide and a methyl ester amino acid led to the tetrahydropyridine-grafted peptide 89 in good yield and excellent diastereoselectivity, which was subsequently deprotected and subjected to a two-component macrolactamization with the propane-1,3-diamine counterpart to afford the heterocycle-peptide hybrid macrocycle 90 without significant epimerization of terminal residues.…”

Section: Mcr-mediated Peptide Functionalization With Ring-closing Groupmentioning

confidence: 99%

Multicomponent Reaction Toolbox for Peptide Macrocyclization and Stapling

2019

Self Cite

View full text Add to dashboard Cite

In the past decade, multicomponent reactions have experienced a renaissance as powerful peptide macrocyclization tools enabling the rapid creation of skeletal complexity and diversity with low synthetic cost. This review provides both a historical and modern overview of the development of the peptide multicomponent macrocyclization as a strategy capable to compete with the classic peptide cyclization methods in terms of chemical efficiency and synthetic scope. We prove that the utilization of multicomponent reactions for cyclizing peptides by either their termini or side chains provides a key advantage over those more established methods; that is, the possibility to explore the cyclic peptide chemotype space not only at the amino acid sequence but also at the ring-forming moiety. Owing to its multicomponent nature, this type of peptide cyclization process is well-suited to generate diversity at both the endo-and exo-cyclic fragments formed during the ring-closing step, which stands as a distinctive and useful characteristic for the creation and screening of cyclic peptide libraries. Examples of the novel multicomponent peptide stapling approach and heterocycle ring-forming macrocyclizations are included, along with multicomponent methods incorporating macrocyclization handles and the one-pot syntheses of macromulticyclic peptide cages. Interesting applications of this strategy in the field of drug discovery and chemical biology are provided.

show abstract

Section: Mcr-mediated Peptide Functionalization With Ring-closing Groupmentioning

confidence: 99%

Multicomponent Reaction Toolbox for Peptide Macrocyclization and Stapling

2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…29 In collaboration with Paixaõ's group, we expanded the diversity of Ugi peptide ligations by developing a highly stereoselective organocatalytic multicomponent approach for the ligation of either two peptides or a peptide and a sugar. 30 As shown in Scheme 5A, the innovation of this method lies in the use of enantiomerically enriched enol−hemiacetals as chiral inputs for the conjugation of isocyanopeptides to carbohydrates and aminopeptides to form peptidic hybrids 9 and 10. Another key report in this field is the Ugi multicomponent ligation of a urea−peptide, a lipidic aldehyde, and a hybrid ribosyl−uridine isocyanide during the synthesis of 11, a potent lipophilic antibacterial analogue of muraymycin, as described by Matsuda and co-workers (Scheme 5B).…”

Section: ■ Oligosaccharide−steroid Conjugationmentioning

confidence: 99%

Multicomponent Reactions in Ligation and Bioconjugation Chemistry

et al. 2018

Self Cite

View full text Add to dashboard Cite

Multicomponent reactions (MCRs) encompass an exciting class of chemical transformations that have proven success in almost all fields of synthetic organic chemistry. These convergent procedures incorporate three or more reactants into a final product in one pot, thus combining high levels of complexity and diversity generation with low synthetic cost. Striking applications of these processes are found in heterocycle, peptidomimetic, and natural product syntheses. However, their potential in the preparation of large macro- and biomolecular constructs has been realized just recently. This Account describes the most relevant results of our group in the utilization of MCRs for ligation/conjugation of biomolecules along with significant contributions from other laboratories that validate the utility of this special class of bioconjugation process. Thus, MCRs have proven to be efficient in the ligation of lipids to peptides and oligosaccharides as well as the ligation of steroids, carbohydrates, and fluorescent and affinity tags to peptides and proteins. In the field of glycolipids, we highlight the power of isocyanide-based MCRs with the one-pot double lipidation of glycan fragments functionalized as either the carboxylic acid or amine. In peptide chemistry, the versatility of the multicomponent ligation strategy is demonstrated in both solution-phase lipidation protocols and solid-phase procedures enabling the simultaneous lipidation and biotinylation of peptides. In addition, we show that MCRs are powerful methods for synchronized lipidation/labeling and macrocyclization of peptides, thus accomplishing in one step what usually requires long sequences. In the realm of protein bioconjugation, MCRs have also proven to be effective in labeling, site-selective modification, immobilization, and glycoconjugation processes. For example, we illustrate a successful application of multicomponent polysaccharide-protein conjugation with the preparation of multivalent glycoconjugate vaccine candidates by the ligation of two antigenic capsular polysaccharides of a pathogenic bacterium to carrier proteins. By highlighting the ability to join several biomolecules in only one synthetic operation, we hope to encourage the biomolecular chemistry community to apply this powerful chemistry to novel biomedicinal challenges.

show abstract

“…37 MCRs have been, for instance, employed as the key step in the synthesis of natural products. 38 As reviewed, 39−41 the chiral induction in MCRs may be a hard task 42 and not always satisfactory selectivities are achieved during the reaction. Approaches such as chiral catalysts, asymmetric organocatalysis, chiral reagents, and others are used to improve both diastereo-and enantioselectivities.…”

Section: ■ Introductionmentioning

confidence: 99%

Combined Role of the Asymmetric Counteranion-Directed Catalysis (ACDC) and Ionic Liquid Effect for the Enantioselective Biginelli Multicomponent Reaction

et al. 2018

View full text Add to dashboard Cite

This work describes new chiral task-specific ionic liquids bearing chiral anions as the catalysts for the enantioselective multicomponent Biginelli reaction. For the first time, the combined role of asymmetric counteranion-directed catalysis (ACDC) and ionic liquid effect (ILE) for the chiral induction in the Biginelli multicomponent reaction is demonstrated. The chiral induction arises from a supramolecular aggregate where the anion and the cation of the catalyst are alongside with a key cationic intermediate of the reaction. Each component of the new catalyst had a vital role for the chiral induction success. The mechanism of an asymmetric version of this multicomponent reaction is in addition demonstrated for the first time using electrospray (tandem) mass spectrometry, ESI-MS(/MS). The analyses indicated the reaction takes place preferentially and exclusively through the iminium mechanism. Unprecedented supramolecular aggregates were detected by ESI-MS and characterized by ESI-MS/MS. No intermediate of the other two possible reactions pathways could be detected. Theoretical calculations shed light on the transition state of the transformation during the key step of the chiral induction and helped to elucidate the roles of the chiral anion (ACDC contribution) and of the imidazolium-containing nonchiral cation derivative (ILE contribution) in the molecular reaction process.

show abstract

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

Cited by 13 publications

References 102 publications

Multicomponent Reaction Toolbox for Peptide Macrocyclization and Stapling

Multicomponent Reaction Toolbox for Peptide Macrocyclization and Stapling

Multicomponent Reactions in Ligation and Bioconjugation Chemistry

Combined Role of the Asymmetric Counteranion-Directed Catalysis (ACDC) and Ionic Liquid Effect for the Enantioselective Biginelli Multicomponent Reaction

Contact Info

Product

Resources

About