Synthesis of [3,5-14C]trachelanthamidine and [5-3H]isoretronecanol and their incorporation into the retronecine moiety of riddelliine in Senecio riddellii.

(+/-)-[3,5-14C]Trachelanthamidine and (+/-)-[5-3H]isoretronecanol, which are diastereomers, were prepared from potassium [14C]cyanide and [5-3H]proline, respectively. These compounds and [1,4-14C]putrescine were administered to Senecio riddellii plants resulting in the formation of labeled riddelliine, in which almost all the radioactivity was located in its retronecine moiety. The activity of the beta-alanine obtained by degradation of the retronecine was consistent with specific labeling of this pyrrolizidine base at the expected positions. The extremely high absolute incorporation (15.1, 22.1%) of trachelanthamidine into riddelliine strongly favors this 1-hydroxymethylpyrrolizidine as the one on the main biosynthetic pathway to retronecine. The lower incorporation (0.75%) of isoretronecanol may represent a minor or aberrant pathway to retronecine.