The role of glycerol in the biosynthesis of the pyridine moiety of nicotine.

In an earlier communication (I), Griffith and Byerrum reported that succinate-2,3-r4C was incorporated into positions 2 and 3 of the pyridine ring of nicotine, and 14C! was distributed essentially equally between the 2 carbon atoms. In addition, ‘4C-labeled glycerol was shown to be efficiently incorporated into the pyridine moiety, and it was suggested that positions 4, 5, and 6 of the ring are derived from this compound (2). However, at that time, the lack of a degradation procedure that could provide for isolation of each carbon of the pyridine ring prevented the location in the ring of l4C incorporated from the labeled glycerol. Such a degradation has now been developed and is described in the present paper. Meanwhile, Friedman and Leete demonstrated that positions 2 and 3 of the pyridine ring of anabasine are formed from the methylene carbons of succinate (3), and that glycerol serves as a precursor for carbon atoms 4, 5, and 6 (4). Similar results were reported by Waller and Henderson (5) and Essery et aE. (6) for the biosynthesis of the pyridone ring of ricinine in Ricinus communis. While we were developing a degradation procedure for the pyridine ring, Leete and Friedman (4) and Christman, Dawson, and Karlstrom (7) described procedures which permitted isolation of each carbon of the pyridine rings of anabasine and nicotine, respectively. However, our degradation provides an independent method for obtaining each carbon of the pyridine ring by a sequence of well established reactions. When our degradation was applied to the pyridine ring of nicotine from plants fed glycerol-2-14C and glycerol-l ,3J4C, incorporation of the carbon atoms of glycerol in toto into positions 4, 5, and 6 of the ring was revealed.