Biosynthesis of the pyridine ring of ricinine.

The most widely distributed substituted pyridine compounds in living systems are the pyridine nucleotides. The nicotinamide moiety (Fig. 1, I) of these compounds arises from the indole nucleus of tryptophan in animals, (1, 2) and Neurospora (3, 4), but not in higher plants (5-7) and certain bacteria (8). Pyridine compounds which might be used to study the biosynthesis of the pyridine nucleus are produced in more than trace quantities by only a few plants. Two naturally occurring alkaloids, ricinine from the castor plant and nicotine from the tobacco plant, are substituted pyridine compounds which have been used in this type of investigation. Ricinine, the toxic alkaloid produced by Ricinus communis L. has the structure Nrmethyl-3-cyano-4-methoxy-2-pyridone (Fig. 1, II). It is present in all parts of the young plant at levels of about 1 mg per g fresh weight and is the only cyano-substituted pyridine compound known to occur naturally. One of the major difficulties in studying the biosynthesis of the pyridine nucleus in plants with isotopes is the lack of suitable degradation procedures. The structure of ricinine suggests that a method could be developed which would permit isolation of each of the carbon atoms of the pyridine ring. A partial degradation of ricinine, based on the ozonolysis of N-methyl-4-methoxy2-pyridone, which permits the separation of the carbon atoms at positions 2 and 6 has been reported (9). Extension of this procedure might make it possible to determine the concentration of isotope in each position of ricinine arising from labeled precursors. In recent years, the biosynthesis of ricinine has been investigated with use of radioactive isotopes. Dubeck and Kirkwood (10) showed that the methyl carbon of methionine serves as a source of the 0and N-methyl groups. Leete’s work (11) indicated that the carboxyl carbon of nicotinic acid becomes the cyano carbon of the alkaloid. His report, which indicates that nicotinic acid ‘gives rise to ricinine, was of interest since it suggested that a study of ricinine formation from small, isotopically labeled molecules would give information applicable to nicotinic acid as well. In similar experiments with the tobacco plant, Dawson et al. (12) showed that the pyridine ring of nicotinic acid is utilized in the formation of the pyridine ring of nicotine. Griffith et al. (13, 14) have indicated that propionate-2-C’*, glycerol-l, 3-C’*, and glycerol-2-C’* are incorporated into the pyridine ring of nicotine. Ortega and Brown (15) reported that glycerol and succinate are precursors of nicotinic acid in Escherichia co&. Conflicting evidence has been reported (6, 9) with regard to the precursor role of lysine in ricinine formation. a+