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.

Enantioselective Catalytic Desymmetrization of Maleimides by Temporary Removal of an Internal Mirror Plane and Stereoablative Over-reduction: Synthesis of (R)-Pyrrolam A

“…Pyrrolam A was shown to have only modest biological activity, with low herbicidal activity and was inactive against both Gram-positive and Gram-negative bacteria, fungi, molds, viruses, worms, protozoa, and tumor cell lines. Since its isolation, there have been a number of reported syntheses, many of which employ a chiral pool approach …”

An insight into recent updates on analytical techniques for bioactive alkaloids

“…9,17 • ing with mACh and 5-HT 2 receptors. 10,27,28 • Quinolizidine alkaloids Quinolizidine alkaloids are heterocyclic compounds with a common nitrogen atom between two six-membered rings. This class of alkaloids is mainly isolated from members of the plant genus Lupinus.…”

“…Important pyrrolizidine alkaloids include echimidine, echihumiline, senecionine, heliotrine, and clivorine. Echimidine and echihumiline alkaloids have significant bioactivity by binding with mACh and 5‐HT 2 receptors 10,27,28 Quinolizidine alkaloids Quinolizidine alkaloids are heterocyclic compounds with a common nitrogen atom between two six‐membered rings.…”

Pyrrolizidine alkaloids

“…The synthesis and biological activity of pyrrolams A-D were reviewed recently. 233 In 2004, an asymmetric synthesis of (R)-pyrrolam A was reported based on asymmetric deprotonation of N-Boc pyrrolidine 166 (Scheme 128) and coupling with ethyl (Z)-3-iodoacrylate. 234 The conditions for N-deprotection and lactamisation had to be carefully optimised in order to obtain (À)-pyrrolam A with high ee and free from alkene isomers and the hydroxylated pyrrolizidine, pyrrolam B.…”