Total Synthesis of Puberulic Acid and Related Congeners Using a Carbohydrate Framework Source

Total synthesis studies of bioactive natural products have served as the foundation in drug discovery research. Particularly, it plays an important role when only a small quantity of materials can be gained through the natural source. Puberulic acid, stipitatic acid, and new troponoid congeners, viticolins A-C were isolated as antimalarial agents from the culture broth of a fungal strain at our institute. Their great biological potential and unique structures led us to undertake the synthetic study of this natural product class. We identified that the core highly oxidized tropone motif in puberulic acid well maps on the common structural feature of carbohydrates, which are often referred to as the “chiral pool”. Instead of taking advantage of the stereochemical information, we were drawn to utilize their carbon-oxygen bond backbone as a “framework source”. In this Account, we summarize previous total syntheses of puberulic acid and detail our efforts toward the gram-scale synthesis of this natural product and related congeners.