Mechanistic Study of the Spiroindolones: A New Class of Antimalarials

Abstract

During the synthesis of the new antimalarial drug candidate NITD609, a high degree of diastereoselectivity was observed in the Pictet-Spengler reaction. By isolating both the <strong>4<em>E</em></strong> and <strong>4<em>Z</em></strong> imine intermediates, a systematic mechanistic study of the reaction under both kinetic and thermodynamic conditions was conducted. This study provides insight into the source of the diastereoselectivity for this important class of compounds.

Keywords

• malaria
• spiroindolones
• NITD609
• Pictet-Spengler reaction
• mechanism