A Synthetic Route to β-Hydroxytyrosine-Derived Tetramic Acids: Total Synthesis of the Fungal Metabolite F-14329

Abstract

3-Acyltetramic acids derived from β-hydroxytyrosine are synthetically challenging. The first route to this structural motif, based upon a condensation between a Meldrum's acid conjugate bearing the acyl side chain, and a β-hydroxytyrosinate, N-protected by an ortho-nitrobenzyl group is presented. This group enables the Dieckmann cyclization of the resulting N-(β-ketoacyl)amino ester, after which it can be removed photolytically without compromising the delicate 3'-hydroxy group. This strategy was applied to the first total synthesis of the fungal metabolite F-14329 (1).

Keywords: F-14329; chaunolidines; natural products; tetramic acids; total synthesis.