HYDROLYSIS RATES OF PYRROLIZIDINE ALKALOIDS DERIVED FROM SENECIO-JACOBAEA

Many of the commonly studied pyrrolizidine alkaloids (PAs) are built u pon the subgroup retronecine (RET), which is released from the parent molecule by either base catalyzed or enzymatic hydrolysis of the ester linkages. The rate of appearance of RET in a hydrolytic study would t hus reflect the fate of hydrolysis for the PA being tested. We have de veloped a gas chromatographic (GC) method to measure the release of RE T from incubations of PAs with the guinea pig carboxylesterase, GPH1. The PAs tested were the following: jacobine (JAB), jacozine (JAZ), ret rorsine (RES), and seneciphylline (SNP). The K(m)s for SNP and JAZ wer e determined to be 64.9 and 349.2 mu M, respectively. In addition, a q ualitative assessment of hydrolytic activity toward a radiolabelled mi xture of retrorsine/riddelliine (RES/RIL) was performed with HPLC and radiometric detection.