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…
Ricardo, M. G.; Vasco, A. V.; Rivera, D. G.; Wessjohann, L. A.;Stabilization of Cyclic β-Hairpins by Ugi-Reaction-Derived N-Alkylated Peptides: The Quest for Functionalized β-TurnsOrg. Lett.217307-7310(2019)DOI: 10.1021/acs.orglett.9b02592
A solid-phase approach including on-resin Ugi reactions was developed for the construction of β-hairpins. Various N-alkylated dipeptide fragments proved capable of aligning antiparallel β-sheets in a macrocyclic scaffold, thus serving as β-hairpin templates. Gramicidin S was used as the model β-hairpin to compare the Ugi-derived β-turns with the type-II′ β-turn. The results show that the multicomponent incorporation of such N-alkylated residues allows for the simultaneous stabilization and exo-cyclic functionalization of cyclic β-hairpins.
Publikation
Puentes, A. R.; Neves Filho, R. A. W.; Rivera, D. G.; Wessjohann, L. A.;Total Synthesis of Cordyheptapeptide ASynlett281971-1974(2017)DOI: 10.1055/s-0036-1588433
The first total synthesis of cordyheptapeptide A is described. The synthesis is accomplished by a convergent approach featuring a combination of peptide coupling and the Ugi reaction for the preparation of the main building blocks and the acyclic precursor. The assembly of an N-methylated fragment by the Ugi reaction comprised the utilization of a convertible isonitrile followed by activation of the C-terminal amide. Two different macrocyclization sites were evaluated, proving greater efficacy the macrolactamization at the site Ile-Tyr, likely due of a more suitable conformational bias of the acyclic precursor having an internal β-turn centered at the N-Me-d-Phe-Pro moiety.
Publikation
Puentes, A. R.; Morejon, M. C.; Rivera, D. G.; Wessjohann, L. A.;Peptide Macrocyclization Assisted by Traceless Turn Inducers Derived from Ugi Peptide Ligation with Cleavable and Resin-Linked AminesOrg. Lett.194022-4025(2017)DOI: 10.1021/acs.orglett.7b01761
A multicomponent approach enabling the installation of turn-inducing moieties that facilitate the macrocyclization of short and medium-size oligopeptides is described. The strategy comprises the Ugi ligation of peptide carboxylic acids and isocyanopeptides in the presence of aldehydes and acid or photolabile amines followed by cyclization and cleavage of the backbone N-substituents to render canonical cyclopeptides. Implementing the approach on solid phase with the use of Rink amide resins led to a new class of backbone amide linker strategy.
Publikation
Morejon, M. C.; Laub, A.; Westermann, B.; Rivera, D. G.; Wessjohann, L. A.;Solution- and Solid-Phase Macrocyclization of Peptides by the Ugi–Smiles Multicomponent Reaction: Synthesis of N-Aryl-Bridged Cyclic LipopeptidesOrg. Lett.184096-4099(2016)DOI: 10.1021/acs.orglett.6b02001
A new multicomponent methodology for the solution- and solid-phase macrocyclization of peptides is described. The approach comprises the utilization of the Ugi–Smiles reaction for the cyclization of 3-nitrotyrosine-containing peptides either by the N-terminus or the lysine side-chain amino groups. Both the on-resin and solution cyclizations took place with good to excellent efficiency in the presence of an aldehyde and a lipidic isocyanide, while the use of paraformaldehyde required an aminocatalysis-mediated imine formation prior to the on-resin Ugi–Smiles ring closure. The introduction of a turn motif in the peptide sequence facilitated the cyclization step, shortened the reaction time, and delivered crude products with >90% purity. This powerful method provided a variety of structurally novel N-aryl-bridged cyclic lipopeptides occurring as single atropisomers