Systematic review of naturally occurring benzylisoquinoline alkaloids (2015-2024): phytochemistry, bioactivity and...

Benzylisoquinoline alkaloids (BIAs), comprising both an isoquinoline moiety and a benzyl group, represent an important class of plant specialized metabolites and are widely distributed in many plant families. According to their core structural features, these compounds can be systematically classified into ten major categories: aporphines, protoberberines, simple benzylisoquinolines, bisbenzylisoquinolines, phenanthrenes, morphinans, phthalideisoquinolines, protopines, spirobenzylisoquinolines, and other related derivatives. Despite the structural complexity of BIA derivatives, the biosynthetic pathways of most subclasses share (S)-reticuline as their common precursor. Pharmacological studies have revealed that BIA ingredients exhibited extensive bioactivities, including antitumor, antibacterial, anti-inflammation, antioxidation, neuroprotection, analgesia, and so on. In 1803, the first BIA, named morphine, possessing a powerful analgesic effect, was discovered by German scientist Sertürner from Papaver somniferum. Subsequently, a large number of natural BIAs were isolated and confirmed. However, scholarly references in this field remain inadequately consolidated, resulting in significant lacunae in the systematic documentation of technological advancements. To address this gap, our research team summarized the BIAs discovered from botanical sources between 2015 and 2024. This work establishes a robust foundation for further exploration and broader applications of BIA derivatives.