Toward the Synthesis of Fluorinated Analogues of HCV NS3/4A Serine Protease Inhibitors Using Methyl α-Amino-β-fluoro-β-vinylcyclopropanecarboxylate as Key Intermediate

Gaëlle Milanole (1) , Floris Andriessen (1) , Gérald Lemonnier (1) , Muriel Sebban (1) , Gaël Coadou (1) , Samuel Couve-Bonnaire (1) , Jean-François Bonfanti , Philippe Jubault (1) , Xavier Pannecoucke (1)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

Synthesis of fluorocyclopropyl building blocks, which constitute the core of various therapeutic agents against the hepatitis C virus, is described. The relevant methyl α-amino-β-fluoro-β-vinylcyclopropanecarboxylate has been used as a key intermediate for the total synthesis of a fluorinated analogue of Simeprevir (TMC 435), a HCV NS3/4A protease inhibitor.

Domaines: Chimie organique; Chimie thérapeutique; Chimie analytique; Catalyse; Chemo-informatique; Chimie théorique et/ou physique

Gaëlle Milanole, Floris Andriessen, Gérald Lemonnier, Muriel Sebban, Gaël Coadou, et al.. Toward the Synthesis of Fluorinated Analogues of HCV NS3/4A Serine Protease Inhibitors Using Methyl α-Amino-β-fluoro-β-vinylcyclopropanecarboxylate as Key Intermediate. Organic Letters, 2015, 17 (12), pp.2968-2971. ⟨10.1021/acs.orglett.5b01216⟩. ⟨hal-01179463⟩