Photoirradiation of dehydropyrrolizidine alkaloids--formation of reactive oxygen species and induction of lipid peroxidation.

Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and human. PAs require metabolic activation to generate pyrrolic metabolites (dehydro-PAs) that bind cellular protein and DNA, leading to hepatotoxicity and genotoxicity, including tumorigenicity. In this study we report that UVA photoirradiation of a series of dehydro-PAs, e.g., dehydromonocrotaline, dehydroriddelliine, dehydroretrorsine, dehydrosenecionine, dehydroseneciphylline, dehydrolasiocarpine, dehydroheliotrine, and dehydroretronecine (DHR) at 0-70 J/cm2 in the presence of a lipid, methyl linoleate, resulted in lipid peroxidation in a light dose-responsive manner. When irradiated in the presence of sodium azide, the level of lipid peroxidation decreased; lipid peroxidation was enhanced when methanol was replaced by deuterated methanol. These results suggest that singlet oxygen is a photo-induced product. When irradiated in the presence of superoxide dismutase, the level of lipid peroxidation decreased, indicating that lipid peroxidation is also mediated by superoxide. Electron spin resonance (ESR) spin trapping studies confirmed that both singlet oxygen and superoxide anion radical were formed during photoirradiation. These results indicate that UVA photoirradiation of dehydro-PAs generates reactive oxygen species (ROS) that mediated the initiation of lipid peroxidation. UVA irradiation of the parent PAs and other PA metabolites, including PA N-oxides, under similar experimental conditions did not produce lipid peroxidation. It is known that PAs induce skin cancer and are secondary (hepatogenous) photosensitization agents. Our results suggest that dehydro-PAs are the active metabolites responsible for skin cancer formation and PA-induced secondary photosensitization.

Ultrasound-promoted synthesis of novel dispirocyclic frameworks from aza-Claisen rearrangements of Baylis-Hillman amines.

A novel tetracyclic frameworks of dispiropyrrolizidines can be obtained in moderate to good yields via the 1,3-dipolar cycloaddition of azomethine ylides with dipolarophiles derived from aza-Claisen rearrangement of Baylis-Hillman amines. The transformations are highly regioselective and stereoselective, affording the desired compounds in reduced time and increased yields under ultrasound irradiation at room temperature. All the products are confirmed by 1H, 13C NMR, IR and MS spectra, while their molecular structures are elucidated by X-ray crystallography of a selected sample.

A facile synthesis of novel pyrrolizidines under classical and ultrasonic conditions.

Novel pyrrolizidines (1) were synthesized from 1,3-dipolar cycloaddition of azomethine ylides and dipolarophiles (4). The reactions were highly diastereoselective and regioselective and were carried out under reflux and ultrasonic condition at room temperature. In general, milder conditions and moderate improvements in rates and reaction times were observed when ultrasonic condition was used. The products were obtained in high yields, and their structures were determined by (1)H and (13)C NMR spectral data and X-ray diffraction.