Convergent Total Synthesis of 16β‐Hydroxylpseudobufarenogin

ABSTRACT 16β‐Hydroxylpseudobufarenogin ( 1 ), isolated from the venom of Bufo bufo gargarizans , has potent anticancer activity. The U‐shaped steroidal structure of 1 possesses a cis ‐fused AB‐ring system, a densely oxidized cis ‐fused CD‐ring system, and a β‐oriented 2‐pyrone at C17. Herein, we present a new convergent strategy for assembling this complex steroidal architecture, culminating in the first total synthesis of 1 in 28 steps from (+)‐Wieland–Miescher ketone. The AB‐ and D‐ring fragments were coupled by Pd/Ag‐promoted Suzuki–Miyaura coupling. Following the Co‐catalyzed hydration of the D‐ring, the C‐ring was stereoselectively constructed by Ir‐catalyzed radical‐relay cyclization. Subsequent C‐ring hydroxylation and installation of the β‐oriented 2‐pyrone through Pd/Cu‐promoted Stille coupling and stereospecific epoxide rearrangement delivered 1 . Because of its high chemo‐ and stereoselectivity, the present methodology would be applicable to the total synthesis of diverse oxygenated bufadienolides by simply altering the fragment structures.