Synthesis of Etrasimod (APD334): Al2O3-Promoted Decarboxylative Rearrangements of Cyclopentenones with Stereochemical Inversion.
J Org Chem
; 89(17): 12524-12532, 2024 Sep 06.
Article
em En
| MEDLINE
| ID: mdl-39150357
ABSTRACT
This study presents an efficient synthesis pathway for etrasimod, starting from (+)-cis-4-acetoxy-2-cyclopenten-1-ol, yielding 5.6% overall with 98% enantiomeric excess. The crucial intermediate, (4R)-anilinocyclopent-2-enone, was derived from the (S)-alcohol/isocyanate adduct through a concerted, Al2O3-promoted decarboxylative rearrangement, which inverted the configuration. A tetracyclic fused lactam was formed via a one-pot acylation-Michael addition, followed by keto α-arylation. Subsequent removal of the oxo group facilitated the synthesis of cyclopenta[b]indol-3-ylacetic acid through a series of reactions, including methanolysis, indoline oxidation, and hydrolysis.
Texto completo:
1
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article