Tetrahydrolipstatin: Thermal and Hydrolytic Degradation

The thermal and hydrolytic degradation of tetrahydrolipstatin (THL, 1 ) was investigated. All main degradation products were isolated, characterized, and synthesized. Labile intermediates unavailable to isolation were detected and identified by GC/MS analysis of their silylated derivatives, and whenever possible, compared with independently prepared reference compounds. The identified degradation products represent at least 97% of the total degradation mixture. Two main reaction pathways arc proposed. Pharmacological data are reported for the degradation mixture and the main degradation products.