Synthesis of alpha-ketobutyrolactones and gamma-hydroxy-alpha-keto acids

Abstract

In connection with the studies for developing new enzymes that could be useful in organic synthesis, practical preparation of racemic and enantiopure forms of gamma-hydroxy-alpha-keto acids has been successfully achieved. For racemic form of gamma-hydroxy-alpha-keto acids, indium-mediated allylation of aldehydes with 2-(bromomethyl)acrylic acid has been employed as a key step. Oxidative cleavage of the thus formed 2-methylenebutyrolactones provided the desired alpha-ketobutyrolactones. Enzymatic resolution of the 7-hydroxy-alpha-methylene esters provided the desired gamma-hydroxy-alpha-methylene acids which were successfully converted to gamma-hydroxy-alpha-ketobutyrolactones in optically pure forms.