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).

Militarinone C and fumosorinone A, 3-oligoenoyltetramic acids produced by insect pathogenic fungi, were synthesized for the first time. The pyrrolidine-2,4-dione ring was closed through a late-stage Dieckmann condensation of N-(β-ketoacyl) derivatives of tyrosine, obtained by its acylation with either thioesters or Meldrum's acid derivatives bearing the all- trans-polyene side chain. The latter was built up from ( S)-citronellol via an Evans methylation and Wittig or HWE olefinations.

Four stereoisomers of the spider-pathogenic fungus metabolite torrubiellone D were synthesized for the first time in 10% overall yield starting from L-tyrosine or D-tyrosine. The 3-decatrienoyl side chain was assembled and attached via (E)-selective HWE and Wittig olefinations. Their antibiotic activities against drug-susceptible Escherichia coli strains differed considerably.