Rationalizing the Origin of Solerone (5-Oxo-4-hexanolide): Biomimetic Synthesis and Identification of Key Metabolites in Sherry Wine

Abstract

A biomimetic synthesis of solerone (5-oxo-4-hexanolide, 1) using both enzymatic and acid-catalyzed reactions was performed. Starting from l-glutamic acid 5-ethyl ester (2) enzymatic oxidative deamination followed by subsequent decarboxylation of the corresponding 2-oxoglutaric acid 5-ethyl ester (3) led to ethyl 4-oxobutanoate (4). In the presence of pyruvate, 4 served as key substrate for a novel acyloin condensation catalyzed by pyruvate decarboxylase (EC 4.1.1.1) from Saccharomyces cerevisiae. Finally, the resulting ethyl 4-hydroxy-5-oxo-hexanoate (5) was easily converted into solerone (1) in the presence of acid. The acyloin condensation of 3 with acetaldehyde to ethyl 5-hydroxy-4-oxohexanoate (6) revealed an alternative route to solerone (1). Acid-catalyzed lactonization of 6 produced 4-oxo-5-hexanolide (7) as well as 5 and 1 via keto−enol tautomerization. Confirming the relevance of the proposed biogenetic pathway, the solerone precursors 2−6 as well as δ-lactone 7 were identified in sherry by GC/MS analysis for the first time. Keywords: Sherry; solerone; biogenesis; pyruvate decarboxylase