Pyrrolozidine alkaloids

Bottcher, F., Adolph, R.-D. and Hartmann, T. 1993. Homospermidine synthase, the first pathway-specific enzyme in pyrrolozidine alkaloid biosynthesis. Phytochemistry, 32 679-689. 

Occasionally toxic compounds can directly damage the hepatic sinusoids and capillaries. One such toxic compound is monocrotaline, a naturally occurring pyrrolozidine alkaloid, found in certain plants (Heliotropium, Senecio, and Crotolaria species). Monocrotaline (Fig. 7.7) is metabolized to a reactive metabolite, which is directly cytotoxic to the sinusoidal and endothelial cells, causing damage and occlusion of the lumen. The blood flow in the liver is therefore reduced and ischemic damage to the hepatocytes ensues. Centrilobular necrosis results, and the venous return to the liver is blocked. Hence, this is known as veno-occlusive disease and results in extensive alteration in hepatic vasculature and function. Chronic exposure causes cirrhosis. 

Occasionally toxic compounds can directly damage the hepatic sinusoids and capillaries. One such toxic compounds is monocrotaline, a naturally occurring pyrrolozidine alkaloid, found in certain plants... 

Pasteels, j. M., M. Rowell-Rahier, T. Randoux, J. C. Braek-MAN, and D. Daloze, Pyrrolozidine alkaloids of probable host-plant origin in the pronotal and elytral secretion of the leaf beetle Oreina cacaliae, Ent. Exp. Appl, 49, 55-58 (1988). 

A considerable number of improvements to existing procedures for the detection, isolation, and separation of pyrrolizidine alkaloid mixtures has been reported. The alkaloids often occur naturally in the form of their N-oxides, and these are usually reduced with zinc in acidic solution to liberate the free bases. An alternative method has been described by Huizing and Malingr 144), which employs a redox polymer on an anion-exchenge resin to give better yields of the free bases. Ion-exchange resins have been used for the extraction (99) and separation 145) of pyrrolozidine alkaloids. 

Dipolarophiles D3. 1,3-Dipolar cycloadditions of suitably functionalized cyclic nitrones with terminal alkenes, which have potential leaving groups X at the end of the alkane chain -(CHo),- (D3), were successfully used for the synthesis of pyrrolozidine, indolizidine and quinolizidine alkaloids, such as (+ )-and (—)-lentiginosine, a potent amyloglucosidase inhibitor (Scheme 2.243) (742). Reductive cleavage of the N-0 bond in the cycloadduct is important for the subsequent cyclization to pyrrolozidines, indolizidines, and quinolizidines. 

---