Scalable Protecting-Group-Free\nTotal Synthesis of\nResibufogenin and Bufalin

A chemoenzymatic\nsynthesis access to resibufogenin and bufalin\nwas developed in seven steps without protecting groups. Starting with\nandrostenedione (AD), an α-OH was introduced directly at C14\nby hydroxylase P-450<sub>lun</sub>, which was further used as the\ndirecting group for hydrogenation to fully control the C17 configuration\nin the β-orientation after Suzuki cross-coupling. Dehydration\nof 14α-OH followed by an epoxidation delivered resibufogenin.\nSimultaneously, bufalin was also obtained via a challenging anaerobic\nMukaiyama hydration.