Biosynthesis of phenanthroindolizidine alkaloids: incorporation of 2-pyrrolidin-2-ylacetophenone and benzoylacetic acid and derivatives

Abstract

2-Pyrrolidin-2-ylacetophenone (12) and its oxygenated derivatives, (13) and (14), bearing ¹⁴C and ³H labels are synthesized and are shown to be intact precursors for the Phenanthroindolizidine alkaloid, tylophorinine (16) in Tylophora asthmatica; the three amines, singly labelled with tritium, are shown to be precursors for tylophorine (3) and tylophorinidine (17). Benzoylacetic acid (9) and p-hydroxybenzoylacetic acid (10)but not 4-hydroxy-3-methoxybenzoylacetic acid, are also precursors for tylophorinine (16). The results allow partial description of the biosynthetic pathways to Phenanthroindolizidine alkaloids. A degradation is described which allowed the location of label in 2-pyrrolidin-2-ylacetophenone, derived from[5-¹⁴C]ornithine, to be established.