Alkollerins

Alkollerins are a class of nitrogen-containing natural products classified as alkaloids. They are defined by a polycyclic core that combines a fused ring system with one or more heteroatoms and a hydrophobic side chain. Across known members, structural variations include different oxidation states and substitutions on the core, contributing to diverse biological activities.

Discovery and naming: The first member, Alkollerin A, was reported in 2003 from several medicinal plants studied for their alkaloid content. The term 'alkollerin' was established to describe this family of molecules sharing the characteristic polycyclic nitrogen-containing framework. Since then additional congeners have been identified from related plant species.

Structure and subclasses: The typical Alkollerin skeleton consists of a fused bicyclic or tetracyclic ring system bearing at least one tertiary amine. Subclasses are distinguished by the oxidation pattern and substituents at defined positions, including hydroxyl, methoxy, and halogenated groups in some members. A rare subclass features a lactam or lactone moiety.

Occurrence and biosynthesis: Alkollerins have been isolated from several plant species across different families, suggesting convergent biosynthetic origins. Isotopic labeling studies indicate that biosynthesis proceeds from amino acids such as tryptophan and tyrosine, followed by oxidative cyclization and tailoring steps mediated by specialized enzymes.

Biological activity and research: In vitro assays have shown antimicrobial, antifungal, and cytotoxic activities for multiple alkollerins, with activity dependent on core topology and functional groups. These properties have attracted interest as potential lead compounds for drug development, prompting efforts in isolation, structural elucidation, and total synthesis.

Chemistry and applications: The synthetic community has pursued total synthesis and analog development to explore structure–activity relationships. While no Alkollerin-based therapeutics have reached clinical use as of now, the family remains a subject of interest for natural product chemists and medicinal chemists.