Scalable Asymmetric Syntheses of Foslevodopa and Foscarbidopa Drug Substances for the Treatment of Parkinson's Disease.
J Org Chem
; 87(4): 1986-1995, 2022 02 18.
Article
em En
| MEDLINE
| ID: mdl-34280307
ABSTRACT
Foslevodopa (FLD, levodopa 4'-monophosphate, 3) and foscarbidopa (FCD, carbidopa 4'-monophosphate, 4) were identified as water-soluble prodrugs of levodopa (LD, 1) and carbidopa (CD, 2), respectively, which are useful for the treatment of Parkinson's disease. Herein, we describe asymmetric syntheses of FLD (3) and FCD (4) drug substances and their manufacture at pilot scale. The synthesis of FLD (3) employs a Horner-Wadsworth-Emmons olefination reaction followed by enantioselective hydrogenation of the double bond as key steps to introduce the α-amino acid moiety with the desired stereochemistry. The synthesis of FCD (4) features a Mizoroki-Heck reaction followed by enantioselective hydrazination to install the quaternary chiral center bearing a hydrazine moiety.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
/
Preparações Farmacêuticas
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article