Biosynthesis of the Cephalotaxus Alkaloids. Investigations of the Early and Late Stages of Cephalotaxine Biosynthesis

Article abstract of DOI:10.1021/ja00523a029

The biosynthesis of the alkaloid cephalotaxine (1) has been investigated by means of precursor incorporation experiments with Cephalotaxus harringtonia.It has been established that cephalotaxine is biosynthesized from one molecule each of tyrosine and phenylalanine in a manner consistent with the hypothesis that 1 is a modified 1-phenethyltetrahydroisoquinoline alkaloid.Incorporation experiments with - and phenylalanine have shown that one of the meta carbon atoms of phenylalanine is lost during the conversion of this amino acid into cephalotaxine.The remaining meta carbon atom is located at C-2 of the alkaloid.Cephalotaxine (1), cephalotaxinone (2), demethylcephalotaxinone (3), and demethylcephalotaxine (4) labeled with carbon-14 at C-3 have been synthesized.Incorporation experiments with these labeled alkaloids have established that cephalotaxine and cephalotaxinone are irreversibly demethylated in vivo.