Unser 10. Leibniz Plant Biochemistry Symposium am 7. und 8. Mai war ein großer Erfolg. Thematisch ging es in diesem Jahr um neue Methoden und Forschungsansätze der Naturstoffchemie. Die exzellenten Vorträge über Wirkstoffe…
Omanische Heilpflanze im Fokus der Phytochemie IPB-Wissenschaftler und Partner aus Dhofar haben jüngst die omanische Heilpflanze Terminalia dhofarica unter die phytochemische Lupe genommen. Die Pflanze ist reich an…
Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Mittersteiner, M.; Pereira, G. S.; Silva, Y.; Wessjohann, L. A.; Bonacorso, H. G.; Martins, M. A. P.; Zanatta, N.;Substituent-driven selective N-/O-alkylation of 4-(trihalomethyl)pyrimidin-2(1H)-ones using brominated enonesJ. Org. Chem.874590-4602(2022)DOI: 10.1021/acs.joc.1c02919
The selective N- or O-alkylation of 4-(trihalomethyl)-pyrimidin-2(1H)-ones, using 5-bromo enones/enaminones as alkylating agents, is reported. It was found that the selectivity toward the N-or O-regioisomer is driven by the substituent present at the 6-position of the pyrimidine ring, thus enabling the preparation of each isomer as the sole product, in 60−95% yields. Subsequent cyclocondensation of the enaminone moiety with nitrogen dinucleophiles led to pyrimidine−azole conjugates in 55−83% yields.
Publikation
Ricardo, M. G.; Vázquéz-Mena, Y.; Iglesias-Morales, Y.; Wessjohann, L. A.; Rivera, D. G.;On the scope of the double Ugi multicomponent stapling to produce helical peptidesBioorg. Chem.113104987(2021)DOI: 10.1016/j.bioorg.2021.104987
The stabilization of helical structures by peptide stapling approaches is now a mature technology capable to provide a variety of biomedical applications. Recently, it was shown that multicomponent macrocyclization is not only an effective way to introduce conformational constraints but it also allows to incorporate additional functionalities to the staple moiety in a one-pot process. This work investigates the scope of the double Ugi multicomponent stapling approach in its capacity to produce helical peptides from unstructured sequences. For this, three different stapling combinations were implemented and the CD spectra of the cyclic peptides were measured to determine the effect of the multicomponent macrocyclization on the resulting secondary structure. A new insight into some structural factors influencing the helicity type and content is provided, along with new prospects on the utilization of this methodology to diversify the molecular tethers linking the amino acid side chains.
Publikation
Wessjohann, L. A.; Morejon, M. C.; Ojeda, G. M.; Rhoden, C. R. B.; Rivera, D. G.;Applications of Convertible Isonitriles in the Ligation and Macrocyclization of Multicomponent Reaction-Derived Peptides and DepsipeptidesJ. Org. Chem.816535-6545(2016)DOI: 10.1021/acs.joc.6b01150
Peptide ligation and macrocyclization are among the most relevant approaches in the field of peptide chemistry. Whereas a variety of strategies relying on coupling reagents and native chemical ligation are available, there is a continuous need for efficient peptide ligation and cyclization methods. Herein we report on the utilization of convertible isonitriles as effective synthetic tools for the ligation and macrocyclization of peptides arising from isocyanide-based multicomponent reactions. The strategy relies on the use of convertible isonitriles—derived from Fukuyama amines—and peptide carboxylic acids in Ugi and Passerini reactions to afford N-alkylated peptides and depsipeptides, respectively, followed by conversion of the C-terminal amide onto either N-peptidoacyl indoles or pyrroles. Such activated peptides proved efficient in the ligation to peptidic, lipidic and fluorescently labeled amines and in macrocyclization protocols. As a result, a wide set of N-substituted peptides (with methyl, glycosyl and amino acids as N-substituents), cyclic N-methylated peptides and a depsipeptide were produced in good yields using conditions that involve either classical heating or microwave irradiation. This report improves the repertoire of peptide covalent modification methods by exploiting the synthetic potential of multicomponent reactions and convertible isonitriles.
Publikation
Vasco, A. V.; Pérez, C. S.; Morales, F. E.; Garay, H. E.; Vasilev, D.; Gavín, J. A.; Wessjohann, L. A.; Rivera, D. G.;Macrocyclization of Peptide Side Chains by the Ugi Reaction: Achieving Peptide Folding and Exocyclic N-Functionalization in One ShotJ. Org. Chem.806697-6707(2015)DOI: 10.1021/acs.joc.5b00858
The cyclization of peptide side chains has been traditionally used to either induce or stabilize secondary structures (β-strands, helices, reverse turns) in short peptide sequences. So far, classic peptide coupling, nucleophilic substitution, olefin metathesis, and click reactions have been the methods of choice to fold synthetic peptides by means of macrocyclization. This article describes the utilization of the Ugi reaction for the side chain-to-side chain and side chain-to-termini macrocyclization of peptides, thus enabling not only access to stable folded structures but also the incorporation of exocyclic functionalities as N-substituents. Analysis of the NMR-derived structures revealed the formation of helical turns, β-bulges, and α-turns in cyclic peptides cross-linked at i, i + 3 and i, i + 4 positions, proving the folding effect of the multicomponent Ugi macrocyclization. Molecular dynamics simulation provided further insights on the stability and molecular motion of the side chain cross-linked peptides.