Pyrrolizidine alkaloid analogues. Synthesis of macrocyclic diesters of (–)-platynecine

Abstract

The first macrocyclic diesters of (–)-platynecine (3) containing 10- and 11-membered rings have been prepared. (–)-Platynecine was obtained by catalytic hydrogenation of readily available (+)retronecine (1). Esterification of (+)-retronecine with different glutaric anhydride derivatives yielded mainly the 9-monoesters of (+)-retronecine. Lactonisation was carried out under high dilution conditions via the S-2-pyridyl thioesters to give the 11-membered macrocyclic diesters [(4)–(7)] of (–)-platynecine. Similar treatment of (–)-platynecine with succinic anhydride, and with cis- and trans-cyclohexane-1,2-dicarboxylic anhydride, produced the 10-membered pyrrolizidine alkaloid analogues (8), (9), and (10), respectively.