Biogenesis of Naturally Occurring Pyrrolizidines

Robinson s original suggestion that the natural pyrrolizidine bases are derived in vivo from two molecules of ornithine (149) has been supported by studies using C-labeled compounds. Ornithine has been shown to be a specific precursor for the pyrrolizidine nucleus present in a variety of alkaloids. The feeding experiments carried out to date are listed in Table I. Three groups of workers have obtained labeled alkaloids after feeding C-labeled ornithines.Hydrolysis of the alkaloid to yield the free base, retronecine (127), has established that almost all the radioactivity is in the base portion. It is likely that ornithine is incorporated into retronecine after decarboxylation to putrescine (150) [Eq. (40)] since labeled putrescine is also specifically incorporated into retronecine (Table I). 

Plant Precursor Alkaloid Total percent incorporation into alkaloid Percent activity in retronecine References 

Robinson, in The Structural Relations of Natural Products, p. 72. Oxford Univ. Press (Clarendon), London and New York, 1955. 

Recently, Bale and Crout have described a double isotope technique for simultaneous measurement of incorporation of two precursors into a natural product. This method was utilized to demonstrate that ornithine is probably a slightly more efficient precursor than arginine for retronecine (127) biosynthesis. 

The author is indebted to Drs. D. H. G. Grout, R. A. Hill, and J. R. Sweeney for valuable discussions and suggestions. 

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The synthesis of pyrrolizidine derivatives by condensation of di-(4-oxo-ra-butyl)amine is considered in Section V in conjunction with the biogenesis of naturally occurring pyrrolizidines. 

Biogenetic pathways leading to naturally occurring pyrrolizidine bases were proposed by Robinson, Schopf, and Lukefi (see, e.g., refs. 119-121) in their publications concerned with the biogenesis of alkaloids. The most probable precursors of the pyrrolizidine system are commonly accepted to be ornithine (176), hydroxyomithine (177), and their biogenetic equivalents. It is noteworthy that ( + )- -hydroxy-jV-methylnorvaline (178) (structurally related to ornithine) was isolated... 

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