14C-radiolabeling of a new steroidal antiandrogen with a C-18 angular methyl extension

Abstract

The synthesis of a ¹⁴C-labeled C-18 functionalized steroid (as referred as EM-6798) that will serve as a probe for the research of novel antiandrogens has been accomplished. This radioactive steroid was obtained in nine steps by coupling racemic N-cyclohexyl-1-(3′-hydroxy[U-¹⁴C]phenyl)propylamine with protected 18-bromomethyl-3,17-androstenedione. Incorporation of the radiolabel on the C-18 side chain was achieved using commercially available 3-bromo[U-¹⁴C]phenol. Alkylation of N-cyclohexyl-1-(3′-hydroxy[U-¹⁴C]phenyl)propylamine with 3-ethylenedioxy-18-bromomethyl-3,17-androstenedione furnished after reduction and deprotection, [phenyl-U-¹⁴C]EM-6798 in a 20% overall yield from 3-bromo[U-¹⁴C]phenol at a specific activity of 156 μCi/mg with 97.9% radiochemical purity as determined by HPLC.