Pyrrolizidine alkaloid analogues. Synthesis of 11-membered macrocyclic diesters of (+)-heliotridine

Abstract

The first synthesis of macrocyclic diesters incorporating (+)-heliotridine has been achieved. Treatment of (+)-heliotridine (1) with different glutaric anhydride derivatives produced mainly the corresponding 9-monoesters of heliotridine. Lactonisation was carried out after formation of the pyridine-2-thiol esters to give a range of 11-membered macrocyclic diesters [(4)–(8)] of heliotridine. The structures of these new pyrrolizidine alkaloid analogues were established by comparison of their ¹H n.m.r. and mass spectra with those of natural macrocyclic pyrrolizidine alkaloids. Attempts to make 10-membered macrocyclic diesters of heliotridine were unsuccessful.