DELAMARE, Aline; NAULET, Guillaume; MUMMADI, Sandeep; GUICHARD, Gilles; COMPAIN, Guillaume

doi:10.5802/crchim.362

Chimie et Biologie des Membranes et des Nanoobjets [CBMN]

NAULET, Guillaume

Chimie et Biologie des Membranes et des Nanoobjets [CBMN]

MUMMADI, Sandeep
Chimie et Biologie des Membranes et des Nanoobjets [CBMN]

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Article de revue

Ce document a été publié dans

Comptes Rendus. Chimie. 2024-12-03, vol. 27, n° G1, p. 385-394

Résumé en anglais

The isobutyl motif is a highly prevalent functional group in medicinal chemistry, commonly present in numerous drugs and bioactive compounds. In biological systems, it notably corresponds to the side chain of the amino acid leucine. The replacement of this branched chain by the hexafluoroisobutyl group provides a significantly more hydrophobic moiety while maintaining a close global morphology. This modification has been overlooked due to the absence of general, simple, and/or efficient synthetic methods for introducing such a group into small molecules, amino acids, peptides, and proteins. In this account, we review our latest contributions to this field, highlighting the development of a general one-step method to incorporate the hexafluoroisobutyl group using a liquid fluorinated reagent. This method involves a tandem mechanism that overcomes the SN2' mechanism usually observed with α-(trifluoromethyl)vinyl groups. This methodology was successfully applied to the synthesis of (S)-5,5,5,5',5',5'-hexafluoroleucine (Hfl). Additionally, we summarize the research conducted on incorporating this valuable amino acid into peptides and proteins. Overall, this work opens new perspectives in organofluorine chemistry, medicinal chemistry, and protein engineering, which are also discussed herein.< Réduire

Mots clés en anglais

Fluoroalkylation

SN2' mechanism

Hydrofluorination

Hexafluoroleucine

Fluorinated peptide

Fluorinated protein

URI

https://oskar-bordeaux.fr/handle/20.500.12278/203968

DOI

http://dx.doi.org/10.5802/crchim.362

Unités de recherche

CBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248

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One-step introduction of the hexafluoroisobutyl group, synthesis of (S)-5,5,5,5',5',5'-hexafluoroleucine, and its incorporation into peptides and proteins

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Résumé en anglais

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