89152-40-9Relevant articles and documents
Stereoselective Synthesis of β-(5-Arylthiazolyl) α-Amino Acids and Use in Neurotensin Analogues
Hap?u, Denisa,Rémond, Emmanuelle,Fanelli, Roberto,Vivancos, Mélanie,René, Adeline,C?té, Jér?me,Besserer-Offroy, élie,Longpré, Jean-Michel,Martinez, Jean,Zaharia, Valentin,Sarret, Philippe,Cavelier, Florine
, p. 1017 - 1024 (2016/03/01)
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.
