Tumor inhibitors. LXIV. isolation and structural elucidation of novel bufadienolides, the cytotoxic principles of Bersama abyssinica

The isolation and structural elucidation of six new cytotoxic bufadienolides from Bersama abyssinica are reported. Bersaldegenin 1,3,5-orthoacetate (1), 16β-hydroxy-bersaldegenin 1,3,5-orthoacetate (10), bersamagenin 1,3,5-orthoacetate (18), and 16β-hydroxybersamagenin 1,3,5-orthoacetate (19) appear to be the first recognized naturally occurring orthoacetates. Interrelations of bersaldegenin 3-acetate (5) with 1 and of 16β-hydroxybersaldegenin 3-acetate (15) with 10 are described. The bersaldegenin derivatives 1 and 10 were interrelated with the corresponding bersamagenin derivatives 18 and 19 via the common reduction products 24 and 25. A novel intramolecular facilitation of equilibration of bersaldegenin 1,3,5-orthoacetate (1) and bersaldegenin 1-acetate (2) is described, and a plausible rationalization which involves participation of the aldehyde group is presented. The parallelism between cytotoxic activity and inhibition of transport ATPase among the foregoing and other bufadienolides is noted, and a speculative rationalization is discussed.