Recent Progress in the Total Synthesis and Biosynthesis of Arborisidine

ABSTRACT

As a significant representative of monoterpenoid indole alkaloids (MIAs) and 1,1‐disubstituted tetrahydro‐β‐carboline (THβC) alkaloids, Arborisidine, since its discovery in 2016 by Kam and coworkers, has emerged as a focal molecule in the field of total synthesis due to its unique pentacyclic cage‐like skeleton and the quaternary carbon center at C(16). Multiple research groups have conducted in‐depth investigations into its total synthesis and successfully developed novel synthetic strategies. These studies have not only advanced the total synthesis and structural modification of this class of MIA natural products but also provided scientific approaches for structure–activity relationship (SAR) studies. Furthermore, with the rapid advancement of synthetic biology, investigations into the biosynthetic pathways of these alkaloids have not only offered innovative synthetic strategies for chemical synthesis but also delivered precise tools for structure‐directed modification, thereby significantly accelerating structure‐based drug design (SBDD). Based on this background, this review summarizes the recent advances in the total synthesis and biosynthetic studies of arborisidine, aiming to provide scientific insights for the synthesis of other family members through comparative analysis of diverse synthetic strategies, as well as to offer methodological support for drug design based on this structural framework.