Pyrrolizidine alkaloid biosynthesis. Incorporation of 2-aminobutanoic acid labelled with 13C or 2H into the senecic acid portion of rosmarinine and senecionine

Abstract

(±)-[3,4-¹³C₂]-2-Aminobutanoic acid 10 and (±)-[3,4-²H₅]-2-aminobutanoic acid 11 are synthesized by alkylating diethyl acetamidomalonate with labelled ethyl iodide followed by acid hydrolysis. These compounds are used to obtain complete labelling patterns for the first time in a necic acid by studying the pyrrolizidine alkaloids rosmarinine 3 and senecionine 1 using NMR spectroscopy. The senecic acid portion 12 of both alkaloids shows equal incorporation of [3,4-¹³C₂]-2-aminobutanoic acid 10 into the two C₅ halves of the C₁₀ acid consistent with formation of senecic acid via two molecules of isoleucine. After feeding [3,4-²H₅]-2-aminobutanoic acid 11, retention of ²H at C-13 and C-20 of both alkaloids 13 confirms that the biosynthesis does not involve keto intermediates at these carbon atoms.