A unified total synthesis route to 18-trideuterated and/or 19-trideuterated testosterone, androstenedione and progesterone

Abstract

A unified total synthesis route has been used to prepare 18- and 19-trideuterated testosterone, androstenedione and progesterone. The 18-trideuterated steroid synthetic method starts with the synthesis of 2-(methyl-d₃)-1,3-cyclopentanedione from CD₃I and 1,3-cyclopentanedione and is subsequently converted into the Hajos-Parrish ketone for synthesis of these trideuterated steroids. The 19-trideuterated steroid synthesis proceeds through non-deuterated Hajos-Parrish ketone with incorporation of the 19-methyl-d₃ group from CD₃I at a later stage of the same synthetic route. Utilization of CD₃I at both the initial and later stages of the synthesis provides a route to 18,19-hexadeuterated steroids. The deuterated steroids are useful for studies of steroid biosynthesis and metabolism.

Keywords: Deuterated androstenedione; Deuterated progesterone; Deuterated steroids; Deuterated testosterone.