Pyrrolizidine relationships

The synthesis of pyrrolizidine alkaloid (-)-rosmarinecine illustrates the power of the fused mode tandem cycloaddition, as shown in Scheme 8.40.180 The all-cA relationship at the three contiguous centers C(l), C(7), and C(7a) can be constructed in a single-pot reaction with correct stereochemistry but C(6) cannot. 

This compound exhibits the same relationship to (3-D-fructofuranose as 1-deoxy-nojirimcin does to D-glucopyranose. In 1979, a polyhydroxyindolizidine alkaloid was isolated from the poisonous fruit of Castanospermum australe, a handsome Australian indigenous tree, and coined castanospermine (8) after its source.28 A compound subsequently isolated from the seeds of this plant was the pyrrolizidine australine (9),29 also found in Alexa leiopetala,30 along with other compounds. These discoveries increasingly supported the hypothesis that imino sugars and their structural relatives might be a fairly common family of natural products, and their widespread... 

A quest for alkaloids the curious relationship between tiger moths and plants containing pyrrolizidine alkaloids... 

Rothschild M. (1979) Mimicry, butterflies and plants. Symb. Bot. Upsal. 22, 82-99. Rothschild M., Aplin R. T., Cockrum P. A., Edgar J. A., Fairweather P. and Lees R. (1979) Pyrrolizidine alkaloids in arctiid moths (Lep.) with a discussion on host plant relationships and the role of these secondary plant substances in the Arctiidae. Biol. J. Linnean Soc. 12, 305-326. 

The toxicity of plants that contain pyrrolizidine alkaloids has been discussed in an earlier volume of this series (163), and the relationship between the toxic nature of the plants and the metabolism of their alkaloids by the victim has been reviewed (164). Since the toxicity of the pyrrolizidine alkaloids in mammals seems to be due to their metabolites rather than to the alkaloids themselves (164), considerable effort has been expended in the identification of the metabolites produced both in vivo and in vitro by mammalian systems. The material summarized in Table V (165-172) is supplementary to that discussed in reference 164. 

FREI, H., LUTHY, J., BRAUCHLI, J ZWEIFEL, U., WURGLER, F.E., SCHLATTER, C., Structure/activity relationships of the genotoxic potencies of sixteen pyrrolizidine alkaloids assayed for the induction of somatic mutation and recombination in wing cells of Drosophila melanogaster. Chem. Biol. Interact , 1992, 83, 1-22. 

The complex relationship between certain genera of butterflies belonging to the nymphalid subfamilies Danainae and Ithomiinae, and pyrrolizidine alkaloid containing plants has been discussed. As well as using alkaloids as precursors of pheromones, male butterflies are believed to use pyrrolizidine alkaloids to produce compounds used for territory marking (see above). 

Some pharmacological properties of pyrrolizidine alkaloids and their relationship to chemical structure. 

Pyrrolizidine alkaloids may be present in some traditional herbs used in Sri Lanka, and this may account for the high incidence of chronic liver disease in this country. Chinese workers are becoming interested in the structure-activity relationships of... 

As a result of these studies we have isolated bioactive compounds belonging to several chemical classes (sesquiterpenes, diterpenes, lignans, diterpenoid alkaloids, pyrrolizidine alkaloids) with selective modes of action and low toxicity. The structure-activity relationships of these compounds have also been established. 

Curtain CC, Edgar JA (1976) The binding of dehydroheliotridine to DNA and the effect of it and other compounds on repair synthesis in main and satellite band DNA. Chem Biol Interact 13 243-256. Hincks JR, Kim HY, Segal HJ, Moljmeux RJ, Stermitz FR, Coulombe RA (1991) DNA cross-linking in mammalian cells by pyrrolizidine alkaloids structure-activity relationships. Toxicol Appl Pharmacol 111 90-98... 

Cooper RA, Huxtable RJ (1999) The relationship between reactivity of metabolites of pyrrolizidine alkaloids and extrahepatic toxicity. Proc West Pharmacol Soc 42 13-16... 

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