Pyrrolizidine alkaloids pyrrolams A-D: A survey of synthetic efforts, biological activity, and studies on their stability

Abstract

Pyrrolam A is a microbial metabolite, structurally related to plant alkaloids of the necine-type, and was isolated from the bacterial strain of Streptomyces olivaceus along with the related alkaloids pyrrolams B-D. The synthesis of (S)- and (R)-pyrrolam A has attracted the attention of chemists in recent years, with 10 syntheses reported to date. The reported routes utilize the advantages of chiral proline as a starting material, with pyrrolidine nucleus as source of one of the two rings on which the second ring has been constructed. This review discusses the isolation of the deceptively simple pyrrolizidine alkaloid pyrrolam A, its biological studies, synthesis, and computational studies on the stability of the double bond in its strained bicyclic skeleton. In addition, the synthesis of pyrrolams B-C and their relationship to pyrrolam A is also discussed.