Synthetic Evolution Toward the Total Synthesis of the Bioactive Natural Polyphenol Cynandione A

초록

Cynandione A (CA) is a natural bioactive polyphenol isolated from Cynanchum wilfordii, which has attracted considerable attention owing to its notable anti-inflammatory activity and multifunctional pharmacological potential. CA has been reported to exhibit immunomodulatory, neuroprotective, and hepatoprotective activities in various models. However, its limited natural abundance and structural complexity hinder extensive biological exploration. Consequently, the total synthesis of CA has been studied extensively. The first total synthesis of CA was reported in 2005, and the original six-step synthesis has evolved into more efficient approaches, including a scalable two-step synthesis and a recently developed one-pot method, which enable gram-scale production with high yield and operational simplicity. A key feature of these strategies is the regioselective conjugate addition of acetylphenol derivatives to an in situ-generated benzoquinone intermediate, governed by electronic and steric factors. This review outlines the synthetic evolution of CA and summarizes its pharmacological activities. The integration of advanced synthetic design with mechanistic pharmacology underscores the value of CA as a promising lead compound for further drug development. Continued optimization of its synthesis and biological validation will facilitate its translation into therapeutic applications.

키워드