Divergent total synthesis of natural products bearing isoflavone and 2-oxabicyclo[3.3.1]nonane skeleton using phloroglucinol and their application in drug discovery

We achieved the divergent total synthesis of 4′-O-methylgrynullarin (1), its derivatives 2–4, scanderone (47), chandalone (48), millexatin F (49), auriculasin (50), derrone (51), alpinumisoflavone (52), 4′-prenyloxyderrone (53), 2′-deoxyisoauriculatin (54), and millexatin I (55) using the Suzuki-Miyaura coupling reaction as the key step starting from phloroglucinol (5). In addition, it is expected that phloroglucinol (5) can be applied to the synthesis of other highly oxygenated natural products. To prove this, we also investigated the total synthesis of rac-betuphenone F (rac-73) from phloroglucinol (5) in only three steps. The 2-oxabicyclo[3.3.1]nonane skeleton, a structural feature of betuphenone F (73), was easily constructed by adding TsOH monohydrate to 75 in acetone.