Pyrrolizidine alkaloid analogues. Synthesis of eleven-membered macrocyclic diesters of retronecine

Abstract

Treatment of (+)-retronecine (1) with 3,3-disubstituted glutaric anhydride derivatives (2) yielded mixtures of the retronecine 7- and 9-monoesters, which were assayed by ¹H n.m.r, spectrometry. Lactonisation of these mixtures was achieved by the Corey–Nicolaou method to give a range of eleven-membered macrocyclic pyrrolizidine diesters (5) with different substituents at C-13. The macrocyclic nature of these pyrrolizidine alkaloid analogues was established by comparison of their ¹H n.m.r. and mass spectra with those of natural pyrrolizidine alkaloids.