Unnatural amino acids, and their synthesis by the late-stage functionalization (LSF) of peptides, play a crucial role in areas such as drug design and discovery. Historically, the LSF of biomolecules has predominantly utilized traditional synthetic methodologies that exploit nucleophilic residues, such as cysteine, lysine or tyrosine. Herein, we present a photocatalytic hydroarylation process targeting the electrophilic residue dehydroalanine (Dha). This residue possesses an alpha,beta-unsaturated moiety and can be combined with various arylthianthrenium salts, both in batch and flow reactors. Notably, the flow setup proved instrumental for efficient scale-up, paving the way for the synthesis of unnatural amino acids and peptides in substantial quantities. Our photocatalytic approach, being inherently mild, permits the diversification of peptides even when they contain sensitive functional groups. The readily available arylthianthrenium salts facilitate the seamless integration of Dha-containing peptides with a wide range of arenes, drug blueprints, and natural products, culminating in the creation of unconventional phenylalanine derivatives. The synergistic effect of the high functional group tolerance and the modular characteristic of the aryl electrophile enables efficient peptide conjugation and ligation in both batch and flow conditions.A photocatalytic hydroarylation of dehydroalanine (Dha) and Dha-containing peptides with versatile arylthianthrenium salts was developed in batch and in flow, enabling expedient scale-up. The mild nature of the photocatalytic approach allowed the diversification of peptides featuring various sensitive functional groups and the effective stitching of Dha-containing peptides with a myriad of arenes and drug scaffolds. image

Photocatalytic Functionalization of Dehydroalanine‐Derived Peptides in Batch and Flow / Kaplaneris, Nikolaos; Akdeniz, Merve; Fillols, Méritxell; Arrighi, Francesca; Raymenants, Fabian; Sanil, Gana; Gryko, Daniel T.; Noël, Timothy. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - 63:19(2024). [10.1002/anie.202403271]

Photocatalytic Functionalization of Dehydroalanine‐Derived Peptides in Batch and Flow

Arrighi, Francesca;
2024

Abstract

Unnatural amino acids, and their synthesis by the late-stage functionalization (LSF) of peptides, play a crucial role in areas such as drug design and discovery. Historically, the LSF of biomolecules has predominantly utilized traditional synthetic methodologies that exploit nucleophilic residues, such as cysteine, lysine or tyrosine. Herein, we present a photocatalytic hydroarylation process targeting the electrophilic residue dehydroalanine (Dha). This residue possesses an alpha,beta-unsaturated moiety and can be combined with various arylthianthrenium salts, both in batch and flow reactors. Notably, the flow setup proved instrumental for efficient scale-up, paving the way for the synthesis of unnatural amino acids and peptides in substantial quantities. Our photocatalytic approach, being inherently mild, permits the diversification of peptides even when they contain sensitive functional groups. The readily available arylthianthrenium salts facilitate the seamless integration of Dha-containing peptides with a wide range of arenes, drug blueprints, and natural products, culminating in the creation of unconventional phenylalanine derivatives. The synergistic effect of the high functional group tolerance and the modular characteristic of the aryl electrophile enables efficient peptide conjugation and ligation in both batch and flow conditions.A photocatalytic hydroarylation of dehydroalanine (Dha) and Dha-containing peptides with versatile arylthianthrenium salts was developed in batch and in flow, enabling expedient scale-up. The mild nature of the photocatalytic approach allowed the diversification of peptides featuring various sensitive functional groups and the effective stitching of Dha-containing peptides with a myriad of arenes and drug scaffolds. image
2024
flow chemistry; late-stage diversification; peptides; photocatalysis; unnatural amino acids
01 Pubblicazione su rivista::01a Articolo in rivista
Photocatalytic Functionalization of Dehydroalanine‐Derived Peptides in Batch and Flow / Kaplaneris, Nikolaos; Akdeniz, Merve; Fillols, Méritxell; Arrighi, Francesca; Raymenants, Fabian; Sanil, Gana; Gryko, Daniel T.; Noël, Timothy. - In: ANGEWANDTE CHEMIE. INTERNATIONAL EDITION. - ISSN 1433-7851. - 63:19(2024). [10.1002/anie.202403271]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1714592
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