21° SEMINARIO QUÍMICA ORGÁNICA IQUIR 2021

SEMINARIO QUÍMICA ORGÁNICA 18-10-21

EXPOSITOR: Qco. Santiago J. Bolivar Avila

TÍTULO: "Scalable Asymmetric Syntheses of Foslevodopa and Foscarbidopa Drug Substances for the Treatment of Parkinson’s Disease".

FUENTE: Alexander D. Huters, James Stambuli, Russell C. Klix, Mark A. Matulenko, Vincent S. Chan, Justin Simanis, David R. Hill,* Rajarathnam E. Reddy, Timothy B. Towne, John R. Bellettini, Brian J. Kotecki, Benoit Cardinal-David, Jianguo Ji, Eric A. Voight, Minshan Shou,
Selvakumar Balaraman, Abhishek Ashok, and Soma Ghosh. J. Org. Chem. 2021, ASAP. 

DOI: https://doi.org/10.1021/acs.joc.1c00905.

DÍA, HORA y LUGAR: Lunes 18 de octubre de 2021, 18:00 h, Plataforma MEET GOOGLE.

Link: meet.google.com/bfh-poxv-bso

RESUMEN: 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.