Synthesis of macrocyclic pyrrolizidine alkaloid analogues from (–)-(7R,8R)-1-chloromethyl-1,2-didehydro-7-hydroxypyrrolizidinium chloride

Abstract

Treatment of the (–)-hydrochloride of (7R,8R)-1-chloromethyl-1,2-didehydro-7-hydroxypyrrolizidine (2) with a series of aromatic and unsaturated anhydrides at room temperature gave the corresponding macrocyclic diesters of retronecine (1). The reaction probably takes place by initial formation of the 7-monoesters of the allylic chloride (2), followed by intramolecular nucleophilic substitution of the chlorine by carboxylate anion. A range of ten-membered [(6)–(12)] macrocyclic diesters of retronecine (1), and one example each of an 11-membered, (13), and 12-membered pyrrolizidine alkaloid analogue, (14), have been prepared.