Pyrrolizidine alkaloid monocrotaline structure

Figure 6.7 The structure of the pyrrolizidine alkaloid monocrotaline and the microsomal enzyme-mediated metabolic activation of the pyrrolizidine alkaloid nucleus.

Monocrotaline (170) has been the subject of extensive metabolic study with mammalian and microbiological systems. Pyrrolizidine alkaloids such as monocrotaline require metabolic activation to the corresponding pyrrole derivatives or dehydro alkaloids before they are capable of forming covalent bonds with critical macromolecules within the cell. The X-ray structure of dehydromonocrotaline has recently been determined (226), and the ability of dihydroretronicine derived from monocrotaline to react with deoxyguanosine has been demonstrated in vitro (225). 

The absolute configuration was also established unequivocally for C-8 of naturally occurring pyrrolizidine bases.88 It was demonstrated in the course of the structural analysis of isoheliotridene (146), obtained by degradation of the alkaloid monocrotaline, that ozonolysis of this compound affords 2-acetylpyrrolidine-l-acetic acid (147).66 The (— )-methyl ester of this acid was condensed with methylmagnesium iodide to give (— )-l-(2-hydroxy-2-methylpropyl)-2-(l-hydroxy-l-methylethyl)pyrrolidine (148). The same glycol (148) was obtained... 

Chem. Soc. 74, 5612 (1952). Configuration Adams, Fles, ibid. 81, 5803 (1959) Robin. Crout, J. Chem. Soc. (C) 1969, 1386. Crystal structure H. Stoekli-Evans, Acta Crystallogr. B35, 231 (1979). Toxicology of monocrotaline and other pyrrolizidine alkaloids McLean, Pharmacol Rev. 22, 429-483 (1970) Allen et aL, Toxicol. Appl. Pharmacol. 23, 470 (1972) R. A. Roth ei al ibid. 60, 193 (1981). Review and evaluation of studies of carcinogenic and toxic action in laboratory animals JARC Monographs 10, 291-302, 333-342 (1976). Comprehensive reviews L. Bull et al. The... 

Otonedne C9H13NO3, Mr 185.22, oil as hydrochloride mp. 146-148 °C, [a]i)-18.5 (CjHjOH) is the N. base of about 30 known pyrrolizidine alkaloids, most of which are of the senecionine structural type (see also senkirkine) and a few of which ate of the monocrotaline structural type. For synthesis, see Lit. ... 

Retronecine (A), which is a simple pyrrolizidine alkaloid, commonly occurs in nature. The formation of the pyrrolizidine structure is presented in Figure 2.35. Retronecine and its P, the senecionine, necine, heliotrine, indicine-A-oxide, malaxine, monocrotaline and absulin, are typical repre-sentatives of this group of alkaloids. Pyrrolizidine alkaloids... 

The absolute configuration of monocrotalic acid (44), the necic acid component of monocrotaline (45), has been elucidated aside from the acid derived from retusamine, whose structure has been defined by X-ray crystallography, this is the first necic acid component of a pyrrolizidine diester alkaloid containing an eleven-membered ring to have its stereochemistry unambiguously established. 

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