256 ALKALOIDS 



shown that amine oxidase preparations from plants can catalyze the formation of hetero- 

 cyclic rings from diamino compounds like putrescine. Leete (63) using 1, 4 -labelled 

 putrescine fed to tobacco found that it was an efficient precursor of the pyrrolidine ring 

 in nicotine. It seems possible to say that the group of C4 and C5 compounds related to 

 ornithine and succinic acid is also closely related to the pyrrolidine alkaloids. The pre- 

 cise precursors have not been identified and may vary from alkaloid to alkaloid and plant 

 to plant. In addition, the pyrrole rings of indole compounds and of porphyrins have quite 

 different origins. 



The precursors of six-membered heterocyclic rings are less certain. It seems 

 likely that pyridine and piperidine rings may arise from quite separate pathways. Leete 

 (64) fed lysine-2-C''' to Nicotiana tabacum (whose alkaloid is nicotine) and to N-glauca 

 (whose alkaloid is anabasine). Isolated nicotine contained no radioactivity. The anaba- 

 sine had activity in the 2-carbon of the piperidine ring, but not in the pyridine ring. For- 

 mation of the piperidine ring from lysine apparently does not involve a symmetrical in- 

 termediate since the 6-carbon contained no label. 



,W2 



CH2 CH2 



CHo *^CHCOOH 



lysine anabasine 



The conversion of lysine to a piperidine ring may take place in two possible ways. 

 Lysine may be directly oxidized to the corresponding a-keto acid which spontaneously 

 undergoes ring closure to A^-piperideinecarboxylic acid (65). Alternatively, lysine may 

 be first decarboxylated and the resulting cadaverine (1, 5-diaminopentane) oxidized and 

 cyclized to A'-piperideine. The conversion of labelled lysine or cadaverine to such pi- 

 peridine alkaloids as coniine, anabasine, lupinine, hydroxylupanine, and sparteine has 

 been amply demonstrated (66, 67, 68). The key role of the enzyme diamine oxidase in 

 catalyzing such transformations is also clear. Mothes et al. (69) have shown that a crude 

 preparation of this enzyme from peas can catalyze conversion of labelled cadaverine into 

 both the pyridine and piperidine rings of anabasine — in contrast to the situation in Nico- 

 tiana (64). 



Except for the last example, it appears that the aromatic-type pyridine ring found 

 in many alkaloids and in the vitamin nicotinic acid is not derived via the lysine-cadaverine 

 pathway. Nicotinic acid and/or nicotinamide have been shown to be good precursors of 

 the pyridine ring in such alkaloids as nicotine (70), and ricinine (71). However, the py- 

 ridine ring is, of course, already present in nicotinic acid; and how it is originally 

 formed remains unknown. There is some indication that C-2, C-3 and the carboxyl group 

 may be derived from a C4 compound such as succinate whereas C-4, C-5, and C-6 may 

 come from a C3 precursor such as glycerol (72, 73). There is convincing evidence that 

 in higher plants nicotinic acid is not made by the pathway: 



tryptophan-'kynurenine-^3-hydroxyanthranilic acid-*nicotinic acid 



even though this pathway has been well-established in fungi (74, 75). 



