Practical and Scalable Synthesis of Curculigoside A and its Structural Analogues as Natural Drug Candidates

Abstract

Curculigosides are naturally occurring phenolic glycosides that have long been recognized for their diverse biological activity and therapeutic properties. The primary member of this class of natural glycosides — curculigoside A — is derived from the roots of the medicinal plant Curculigo orchioides Gaertn., which is extensively used in the traditional Indian and Chinese medicine. This compound has gained significant attention in recent years due to its potent antioxidant properties and its therapeutic potential for the treatment of inflammation, arthritis, tissue ischemia, osteoporosis, and neurodegenerative diseases. However, broader medicinal studies are currently hampered by the low availability of curculigosides. Extraction and isolation from plants yields only minimal amounts of pure compounds while requiring the use of copious amounts of solvents for extractions and several chromatographic purifications. In this work, we demonstrate a convenient synthetic route to curculigoside A and its structural analogues starting from readily available substrates. The disclosed synthetic route was also optimized for large-scale synthesis, allowing isolation of 2.23 g of pure curculigoside A. It is our hope that this scalable access to curculigosides will enable future biological and medicinal studies of this class of natural products.