Formation of 3-hydroxy-4,5-dimethyl-2(5H)-furanone (sotolone) from 4-hydroxy-L-isoleucine and 3-amino-4,5-dimethyl-3,4-dihydro-2(5H)-furanone

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 degrees C for 1 h. The amount of sotolone was quantified by stable isotope dilution assays using C-13(2)-labeled sotolone as internal standard and GC-MS operating in the selected ion monitoring mode. In general, alpha-ketoaldehydes were found to be more reactive than alpha-diketones. Methylglyoxal gave rise to about 64 mu g sotolone per mg 1 (7.4 mol %) compared to less than 1 mu g (<0.1 mol %) when reacted with 2,3-pentanedione. Using 2 as the starting material, the yields were increased to 274 mu g (35.9 mol %) and 5.4 mu g (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 degrees C. The yield increased over a period of 10 h to about 210 mu g/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.