Formation of 3-Hydroxy-4,5-dimethyl-2(5<i>H</i>)-furanone (Sotolone) from 4-Hydroxy-<scp>l</scp>-isoleucine and 3-Amino-4,5-dimethyl-3,4-dihydro-2(5<i>H</i>)-furanone

Abstract

The proposed formation of 3-hydroxy-4,5-dimethyl-2(5H)-furanone (sotolone) from 4-hydroxy-l-isoleucine (1) and the corresponding lactone 3-amino-4,5-dimethyl-3,4-dihydro-2(5H)-furanone (2) by thermally induced oxidative deamination was corroborated. The formation of sotolone was studied in model systems by reacting 1 or 2 with different carbonyl compounds in a phosphate buffer at pH 5 at 100 °C for 1 h. The amount of sotolone was quantified by stable isotope dilution assays using 13C2-labeled sotolone as internal standard and GC-MS operating in the selected ion monitoring mode. In general, α-ketoaldehydes were found to be more reactive than α-diketones. Methylglyoxal gave rise to about 64 μg sotolone per mg 1 (7.4 mol %) compared to less than 1 μg (<0.1 mol %) when reacted with 2,3-pentanedione. Using 2 as the starting material, the yields were increased to 274 μg (35.9 mol %) and 5.4 μg (0.7 mol %), respectively. The optimum pH of the reaction with HIL was 5, representing the best compromise between the lactonization step and the amino−carbonyl reaction. Significant amounts of sotolone were generated only at temperatures higher than 70 °C. The yield increased over a period of 10 h to about 210 μg/mg 1 (23.8 mol %). The Strecker degradation of 1, resulting in 3-hydroxy-2-methylbutanal, was a competitive reaction to the formation of sotolone. Keywords: 3-Hydroxy-4,5-dimethyl-2(5H)-furanone (sotolone); 4-hydroxy-l-isoleucine; oxidative deamination; Strecker degradation; quantification by isotope dilution assay; model system studies; synthesis