Indolizidine

Indolizidine is a bicyclic heterocyclic chemical scaffold consisting of a pyrrolidine ring fused to a piperidine ring, resulting in a saturated framework that contains two nitrogen atoms. This core structure serves as the basis for a large family of natural products known as indolizidine alkaloids, which feature various substitutions around the fused rings.

The indolizidine skeleton is typically fully saturated, and its natural derivatives include secondary and tertiary amines. The fused ring system allows a range of stereochemical arrangements, giving rise to numerous distinct alkaloids with diverse substituents and functional groups. Because of the two nitrogen atoms and the ring fusion, many indolizidine alkaloids exhibit notable basicity and a propensity to interact with biological enzymes and receptors.

Occurrence and significance: Indolizidine alkaloids are found in a variety of plants, particularly among locoweeds of the Astragalus and Oxytropis genera and in Castanospermum australe, among others. They often function as ecological defenses against herbivores. Several well-known members have been studied for their biological activities, such as glycosidase inhibition. Swainsonine inhibits Golgi alpha-mannosidase II, while castanospermine inhibits glucosidases, making these compounds of interest in biomedical research. Some indolizidine alkaloids also exhibit antifeedant or cytotoxic properties.

Biosynthesis in nature typically derives the indolizidine framework from amino acid precursors, leading to the diverse array of natural products within this class. The core skeleton continues to be a focus of synthetic and medicinal chemistry due to its unique architecture and biological activity.