A copper-catalyzed arylation of tryptophan derivatives is reported. The reaction proceeds with high site- and diastereoselectivity to provide aryl pyrroloindoline products in one step from simple starting materials. The utility of this transformation is highlighted in the five-step syntheses of the natural products (+)-naseseazine A and B.
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http://dx.doi.org/10.1021/ja4023557 | DOI Listing |
Org Lett
January 2025
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
Natural product biosynthesis is nature's tinkering ground for developing new enzymes that can achieve chemical transformations that are outside the purview of traditional chemical catalysis. Herein we describe a genome mining approach that leads to the discovery of a halogenase that regioselectively brominates a tryptophan side chain indole for a macrocyclic peptide substrate, enabling downstream chemical arylation by Suzuki-Miyaura coupling. The halogenase was found to prefer a macrocyclic peptide substrate over a linear peptide.
View Article and Find Full Text PDFOrg Lett
May 2024
Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, U.K.
We introduce a novel and straightforward methodology for photoredox arylation of an indole scaffold using aryldiazonium salts under mild and metal-free conditions. Our approach enables the regioselective and chemoselective introduction of several aryl groups to the C(2) position of indoles and tryptophan, even in competition with other amino acids. This approach extends to the late-stage functionalization of peptides and lysozyme, heralding the unprecedented arylation of tryptophan residues in wild-type proteins and offering broad utility in chemical biology.
View Article and Find Full Text PDFOrg Lett
December 2023
School of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Thiazoloindole α-amino acids have been synthesized in four steps from tryptophan using a dual-catalytic thiolation reaction and a copper-mediated intramolecular N-arylation process. Late-stage diversification of the thiazoloindole core with electron-deficient aryl substituents produced chromophores that on one-photon excitation displayed blue-green emission, mega-Stokes shifts, and high quantum yields. The thiazoloindole amino acids could also be excited via two-photon absorption in the near-infrared, demonstrating their potential for biomedical imaging applications.
View Article and Find Full Text PDFJ Am Chem Soc
December 2023
Laboratory for Sustainable Organic Synthesis and Catalysis, Department of Chemistry, Federal University of São Carlos─UFSCar, Rodovia Washington Luís, km 235, SP-310, São Carlos, São Paulo 13565-905, Brazil.
Postsynthetic diversification of peptides through selective modification of endogenous amino acid side chains has enabled significant advances in peptide drug discovery while expanding the biological and medical chemistry space. However, current tools have been focused on the modification of reactive polar and ionizable side chains, whereas the decoration of aromatic systems (e.g.
View Article and Find Full Text PDFNanoscale Adv
January 2023
Instituto de Catálisis y Petroleoquímica (ICP), CSIC C/Marie Curie 2 28049 Madrid Spain
The effect of the temperature in the synthesis of Pd nanoparticles in the metal-enzyme biohybrids is evaluated. The effect on the formation, size, and morphology of nanoparticles was evaluated using B lipase as the protein scaffold. XRD analyses confirmed the formation of crystalline Pd(0) as the metal species in all cases.
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