Synthesis of Bufalitoxin and Bufotoxin

Completion of a formal total synthetic route to the toad venom constituents bufotalin (8), cinobufagin (2a), bufalitoxin (3f), and bufotoxin (la) has been accomplished. Bufalin (3a) was employed as relay and converted to 14-dehydrobufalin 3-acetate (4). Selective oxidation of olefin 4 with a chromium trioxide-pyridine reagent afforded 16-ketone 5, which we had previously transformed to bufotalin (8) and thence to cinobufagin (2a). Condensation of bufalin (3a) with suberic anhydride followed by a mixed carbonic anhydride reaction sequence using arginine monohydrochloride yielded bufalitoxin (3f), and an analogous route from bufotalin (8) led to bufotoxin (la).