Pyrrolizidine alkaloid analogues. Synthesis of macrocyclic diesters of (+)-(1R,6R,8R)-6-hydroxy-1-hydroxymethylpyrrolizidine

Abstract

Macrocyclic diesters of (+)-(1R,6R,8R)-6-hydroxy-1-hydroxymethylpyrrolizidine have been synthesized in optically active form. The pyrrolizidinediol (7) was prepared from (2S,4R)-4-hydroxyproline (4) and then esterified with different glutaric anhydride derivatives to yield mainly the corresponding 9-mono esters. Lactonisation was achieved under high dilution conditions after formation of the S-2-pyridyl thin esters to give a range of 12-membered macrocyclic diesters [(9)–(14)] of (+)-(1R,6R,8R)-6-hydroxy-1-hydroxymethylpyrrolizidine. Similar treatment of the diol (7) with succinic anhydride produced an 11-membered system (15).