Characterization and Lifetime Dietary Risk Assessment of Eighteen Pyrrolizidine Alkaloids and Pyrrolizidine Alkaloid N-Oxides in New Zealand Honey

Pyrrolizidine alkaloids (PAs) are a large group of botanical toxins of concern, as they are considered genotoxic carcinogens, with long-term dietary exposure presenting an elevated risk of liver cancer. PAs can contaminate honey through honeybees visiting the flowers of PA-containing plant species. A program of monitoring New Zealand honey has been undertaken over several years to build a comprehensive dataset on the concentration, regional and seasonal distribution, and botanical origin of 18 PAs and PA N-oxides. A bespoke probabilistic exposure model has then been used to assess the averaged lifetime dietary risk to honey consumers, with exposures at each percentile of the model characterized for risk using a margin of exposure from the Joint World Health Organization and United Nations Food and Agriculture Organization Expert Committee on Food Additives (JECFA) Benchmark Dose. Survey findings identify the typical PA types for New Zealand honey as lycopsamine, echimidine, retrorsine and senecionine. Regional and seasonal variation is evident in the types and levels of total PAs, linked to the ranges and flowering times of certain plants. Over a lifetime basis, the average exposure an individual will receive through honey consumption is considered within tolerable levels, although there are uncertainties over high and brand-loyal consumers, and other dietary contributors. An average lifetime risk to the general population from PAs in honey is not expected. However, given the uncertainties in the assessment, risk management approaches to limit or reduce exposures through honey are still of value.     

Alkaloid anticancer agents

Patent Summary

A process is claimed for the preparation of desethyldi-hydronavelbine. The process consists of a partial total synthesis of one of the dimeric components and allows for the synthesis of navelbine analogues. Navelbine has application in cancer chemotherapy, having broader antitumour activity and lower neurotoxicity than the known agents vinblastine and vincristine.

(+)-18′ S-4′-desethyl-4′-deshydroxy-7′-norviblastine was tested in vitro for antitumour activity in comparison with the 18′ (R)-epimer, vinblastine and navelbine. The IC50 values were determined in a 72 hour cytotoxicity assay and the respective values (μg/ml) were 0.0005, no activity, 0.0005 and 0.005, respectively. The total synthesis of desethyldihydronavelbine is described and the preparation of dihydrodesethylnavel-bine is also described. Altogether fifteen compounds are described, including their intermediates.     

Ein psychotropes Alkaloid aus Pilocarpus organensis

A Psychotropic Alkaloid from Pilocarpus Organensis The leaves of the new species Pilocarpus organensis, which was described recently, contain N,N-dimethyl-5-methoxytryptamine (O-methylbufotenine) as the main alkaloid.     

Enantioselective Hydrosilylation and Hydrogenation of Alkaloid Precursors

Enantioselective hydrosilylations of the 3,4-dihydropyrrole derivatives 1a – c and 5 with in-situ catalysts consisting of [Rh(cod)Cl]₂ and optically active phosphines yield the N-silyl compounds 2a – c and 6 in up to 66.1% ee. The N-silyl derivatives were treated with acetic formic anhydride or trifluoroacetic anhydride to give the N-formyl and N-trifluoroacetyl compounds 3a–c, 4a–c, 7 , and 8 . The alkaloids nicotine and macrostomine were synthesized with 63.3 and 33% ee by reduction of the N-formyl compounds 8 and 12 . Enantioselective hydrogenations of the N-formyl and N-trifluoroacetyl-2-phenylpyrrolines 14 and 15 with the same in-situ catalysts produce the cyclic amides 3a and 4a in up to 36.1% ee.     

Indole Alkaloid beta-Carboline-1-propionic Acid.

The total synthesis of ethyl beta-carboline-1-propionate has been described and its ability to bind toward benzodiazepine and GABA receptors has been studied. It has been suggested that beta-carboline-1-propionic acid is the true natural product, its ester derivatives are only artefacts of the isolation procedure.     

Alkaloid Screening of Panamanian Plants. I

Abstract

The Flora of Panamá is one of the richest in the world (Schultés, 1972) as plants from South and Central America as well as from the Caribbean area can be found here. However, with the exception of research carried out by our group, the Panamanian plants have not been subjected to any form of systematic chemical or pharmacological study. As a part of our continuing interest in the unexplored National Flora, we initiated a screening program to make a preliminary selection of plants for future phytochemical studies, and to uncover new sources of phytoconstituents which may eventually be found to have biological activities. Our initial studies, reported at this time, involve screening the plant extracts for alkaloids.

Plant collections were made over a period of about three years, beginning in 1973, from different parts of the country.     

蝙蝠葛中一新双苄基异喹啉生物碱

防己科植物蝙蝠葛（ＭｅｎｉｓｐｅｒｍｕｍｄａｕｒｉｃｕｍＤＣ．）根茎中的脂溶性酚性生物碱具有抗多种实验性心律失常活性〔１〕,近年研究表明,其主成分蝙蝠葛碱（ｄａｕｒｉｃｉｎｅ,１）和蝙蝠葛苏林碱（ｄａｕｒｉｓｏｌｉｎｅ,２）延长心肌动作电位时呈使用...     

Alkaloid distribution in some african rauvolfia species

The distribution of indole alkaloids in the leaves, stems and roots of 10 African mainland RAUVOLFIA species is summarised and the interrelationships of the alkaloid types discussed.