Ammonium carboxylates in the ammonia-Ugi reaction: one-pot synthesis of α,α-disubstituted amino acid derivatives including unnatural dipeptides.
Org Biomol Chem
; 22(34): 6999-7005, 2024 08 28.
Article
en En
| MEDLINE
| ID: mdl-39118586
ABSTRACT
Despite the remarkable developments of the Ugi reaction and its variants, the use of ammonia in the Ugi reaction has long been recognized as impractical and unsuccessful. Indeed, the ammonia-Ugi reaction often requires harsh reaction conditions, such as heating and microwave irradiation, and competes with the Passerini reaction, thereby resulting in low yields. This study describes a robust and practical ammonia-Ugi reaction protocol. Using originally prepared ammonium carboxylates in trifluoroethanol, the ammonia-Ugi reaction proceeded at room temperature in high yields and showed a broad substrate scope, thus synthesizing a variety of α,α-disubstituted amino acid derivatives, including unnatural dipeptides. The reaction required no condensing agents and proceeded without racemization of the chiral stereocenter of α-amino acids. Furthermore, using this protocol, we quickly synthesized a novel dipeptide, D-Leu-Aic-NH-CH2Ph(p-F), which exhibited a potent inhibitory activity against α-chymotrypsin with a Ki value of 0.091 µM.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dipéptidos
/
Aminoácidos
/
Amoníaco
Idioma:
En
Revista:
Org Biomol Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido