Lasiocarpinic acid

Lasiocarpinic acid was considered to be esterified with the allylic hydroxyl of heliotridine because of its isolation in the hydrogenolysis of the alkaloid. The angelic acid was considered to be esterified with the 7-hydroxyl of heliotridine since this linkage was not easily reduced. 

The pulmonary oedema produced in rats by dehydromonocrotaline has been studied by electron microscopy. Tritiated dehydroretronecine has been used in studies of the binding of this metabolite to macromolecules. Studies in vivo with rhesus monkeys revealed preferential binding of dehydroretronedne to the protein of gastric mucosa. Much less radioactivity was found associated with RNA and DNA. Binding in vitro to calf thymus DNA and bovine serum albumin took place most readily under acidic conditions. Tritiated dehydroheliotridine has been used to study the preferential depression of satellite DNA synthesis by this metabolite in cultured sheep lymphocytes and ovine kidney cells. The mechanism of the antimitotic action of lasiocarpine and dehydroheliotridine has been investigated in... 

The total synthesis of (+ )-dehydroheliotridine (4), a toxic metabolite of the pyrrolizidine alkaloids (e.g. lasiocarpine and heliotrine), has also been described.2 The pyrrole ring was obtained by reaction of l,6-dihydroxy-2,5-dicyanohexa-l,3,5-triene-l,6-dicarboxylic ester (5) with j3-alanine, which afforded the N-substituted pyrrole ester (6), together with the appropriate amide of oxalic acid. Careful hydrolysis of (6) with dilute alkali afforded the related tricarboxylic acid, which was converted, by Dieckmann cyclization, hydrolysis and decarboxylation, into the keto-acid (7). Esterification of (7) with diazomethane, followed by reduction with lithium aluminium hydride, finally afforded ( )-dehydroheliotridine (4), identical, except in optical rotation, with dehydroheliotridine obtained earlier by Culvenor et al.3... 

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