Stereoselective Synthesis of β-(5-Arylthiazolyl) α-Amino Acids and Use in Neurotensin Analogues - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue European Journal of Organic Chemistry Année : 2016

Stereoselective Synthesis of β-(5-Arylthiazolyl) α-Amino Acids and Use in Neurotensin Analogues

Résumé

A series of new unnatural amino acids bearing a β-arylthiazole side chain was synthesized by exploiting a diastereoselective alkylation starting from glycine tert-butyl ester Schiff base with hydroxypinanone as the chiral inducer. This strategy afforded β-arylthiazole alanines in good chemical yields and with 98 % ee. Due to their aromatic properties, these newly generated amino acids were used to prepare neurotensin (NT)[8–13] analogues by serving as replacements for the native Tyr11 residue. Incorporation of the (L)-(+)-(β-phenylthiazol-4-yl)alanine residue at NT[8–13] position 11 improved plasma stability and selectivity towards NTS1, while also preserving native receptor binding affinity and biological activity. New β-arylthiazole alanines were synthesized in good chemical yields and with 98 % ee using a diastereoselective alkylation; these alanine derivatives were then used as Tyr11 replacements in the construction of neurotensin (NT)[8–13] analogues. The new NT analogues showed improved plasma stability and selectivity towards NTS1 thus preserving the hypotensive properties of the native peptide.

Domaines

Chimie

Dates et versions

hal-03566472 , version 1 (11-02-2022)

Identifiants

Citer

Denisa Hapău, Emmanuelle Rémond, Roberto Fanelli, Mélanie Vivancos, Adeline René, et al.. Stereoselective Synthesis of β-(5-Arylthiazolyl) α-Amino Acids and Use in Neurotensin Analogues. European Journal of Organic Chemistry, 2016, 2016 (5), pp.1017-1024. ⟨10.1002/ejoc.201501495⟩. ⟨hal-03566472⟩
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