Relationship between ornithine decarboxylase-inducing activity and configuration at C-4 in phorbol ester derivatives

Measurements were made of induction of ornithine decarboxylase activity after painting mouse skin with 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate and its two epimeric 4-deoxy-analogs, 12-O-hexadecanoyl-4-deoxy-16-hydroxyphorbol-13-acetate and 12-O-hexadecanoyl-4-deoxy-4 alpha-16-hydroxyphorbol-13 acetate. The inductive activities of HHPA and 4-deoxy-HHPA were similar, but 4-deoxy-4 alpha HHPA had no inductive activity. These findings on natural phorbol esters confirm that both the 4 beta-hydrogen and the 4 beta-hydroxyl in phorbol esters are essential for ODC-inducing activity. The interactions of 4-deoxy-HHPA and 4-deoxy-4 alpha-HHPA with a possible receptor are discussed.