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Stereoselective Synthesis of β‐(5‐Arylthiazolyl) α‐Amino Acids and Use in Neurotensin Analogues
Author(s) -
Hapău Denisa,
Rémond Emmanuelle,
Fanelli Roberto,
Vivancos Mélanie,
René Adeline,
Côté Jérôme,
BessererOffroy Élie,
Longpré JeanMichel,
Martinez Jean,
Zaharia Valentin,
Sarret Philippe,
Cavelier Florine
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201501495
Subject(s) - chemistry , neurotensin , residue (chemistry) , amino acid , alanine , stereochemistry , glycine , stereoselectivity , alkylation , side chain , selectivity , dehydroalanine , chemical synthesis , enantioselective synthesis , neurotensin receptor , organic chemistry , receptor , biochemistry , in vitro , neuropeptide , polymer , catalysis
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.