Asymmetric Formal Synthesis of the Long-Acting DPP-4 Inhibitor Omarigliptin.
J Org Chem
; 82(17): 9023-9029, 2017 09 01.
Article
en En
| MEDLINE
| ID: mdl-28776371
A highly efficient asymmetric synthesis of the key tetrahydropyranol intermediate of DPP-4 inhibitor omarigliptin (1) is described. The successful development of a protecting-group- and precious-metal-free synthesis was achieved via the discovery of a practical asymmetric Henry reaction and the application of a one-pot nitro-Michael-lactolization-dehydration through-process. Other features of the synthesis include a highly efficient MsCl-mediated dehydration and a crystallization-induced dynamic resolution for exceptional ee and dr upgrade. The synthesis of this complex intermediate utilizes simple starting materials and proceeds in four linear steps.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piranos
/
Inhibidores de la Dipeptidil-Peptidasa IV
/
Compuestos Heterocíclicos con 2 Anillos
Idioma:
En
Revista:
J Org Chem
Año:
2017
Tipo del documento:
Article
Pais de publicación:
Estados Unidos