This article describes the procedure for the synthesis of chiral tetramic acids by preparation of (S)‐5‐benzylpyrrolidine‐2,4‐dione from L‐phenylalanine methyl ester hydrochloride. It presents some important points to be considered before carrying out the procedure. The tetramic acid (pyrrolidine‐2,4‐dione) scaffold can be found embedded within a plethora of natural products which exhibit a wide range of bioactivities, including powerful antibiotic, antiviral, cytotoxic, and fungicidal properties, as well as inhibition of tumor growth. The article provides a general overview of tetramic acid chemistry and highlights the utility of developed synthetic methodologies aimed at the construction of the pyrrolidine‐2,4‐dione core as well as the challenges encountered when applying these methods towards more complex systems. It also presents a discussion on the application of tetramic acids and the Lacey‐Dieckmann cyclization to total synthesis.
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