Pyrrolizidine Alkaloid Analogues. Synthesis of Macrocyclic Diesters of (+/-)-Synthanecine A from (+/-)-3-Chloromethyl-2-hydroxymethyl-1-methyl-2,5-dihydropyrrolium Chloride

Article abstract of DOI:10.1039/P19880001169

Reaction of 2,3-bis(hydroxymethyl)-1-methyl-2,5-dihydropyrrole<(+/-)-synthanecine A> (3) with thionyl chloride produces (+/-)-3-chloromethyl-2-hydroxymethyl-1-methyl-2,5-dihydropyrrolium chloride (11), which was treated with a series of anhydrides and base at room temperature to give the corresponding 6-monoesters of (+/-)-synthanecine A.Intramolecular nucleophilic substitution of the chlorine by carboxylate anion in the presence of base (DBU) gives the corresponding macrocyclic diesters of (+/-)-synthanecine A.The pyrrolizidine alkaloid analogues <(6), (7), and (16)-(20)> are prepared in better yields than using Corey-Nicolaou lactonisation conditions.A range of new 10-membered <(8)-(10) and (12)-(14)> and 11-membered <(15) and (21)> macrocyclic diesters of (+/-)-synthanecine A has been prepared.