Application of heterogeneous catalysts in the first steps of the oseltamivir synthesis

Abstract

The first steps of oseltamivir synthesis from quinic acid involve acetalization and ester formation. These reactions are catalyzed by either acids or bases, which may be accomplished by heterogeneous catalysts. Sulfonic solids are efficient acid catalysts for acetalization and esterification reactions. Supported tetraalkylammonium hydroxide or 1,5,7-triazabicyclo[4.4.0]dec-5-ene are also efficient base catalysts for lactone alcoholysis and in this work, these catalysts have been applied in two alternative synthetic routes that lead to oseltamivir. The classical route consists of an acetalization, followed by a lactonization, and then a lactone alcoholysis. This achieves a 66% isolated yield. The alternative route consists of esterification followed by acetalization and is only efficient when an acetone acetal is used.