Concise Total Synthesis of rac-Betuphenone F

Betuphenone F (6) is a natural product isolated from the bark of Betula alnoides Ham. ex D. Don (Betulaceae) and structurally determined by S. Awale et al. in 2021. Betuphenone F (6) has the potential to be a new-generation anti-cancer agents based on anti-austerity, as it showed preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions (PC50 value of 4.9 mu M). We succeeded in constructing the 2-oxabicyclo[3.3.1]nonane skeleton, which is a structural feature of betuphenone F (6), by exposing intermediate 9 to acid, and achieved the first total synthesis of rac-bethuphenone F (6) from phloroglucinol (7) in only three steps.