The absolute configuration of the enantiomers of glutethimide and aminoglutethimide

Abstract

Aminoglutethimide (Elipten¿ CIBA) was resolved into the optical antipodes I and II. The endocrinological properties and the absolute configuration of both enantiomers I and II were determined. Most of the steroidal synthesis inhibition was found in the (+) enantiomer II. On the basis of circular dichroism, the R-configuration was assigned to the (+) enantiomer II.

PIP: The absolute configurations of glutethimide, and of aminoglutethimide, a sedative drug that inhibits progesterone and corticosteroid secretion were determined. Dextrorotatory aminoglutethimide (+) shown to be 2-3 times as active as levorotatory aminoglutethimide in inhibiting corticosteroid release in rats, and it reduced plasma progesterone 78% in gonadotropin-primed immature rats when injected iv. Aminoglutethimide was resolved by recrystalizing the tartrate salts from methanol and determining the optical rotation. Glutethimide was prepared and its circular dichroism and optical rotatory dispersion curves compared with S(-)2-ethyl-2-phenyl-succinimide and S(-)-2-methyl-2-phenyl-glutaric anhydride, respectively. Since the S-configuration was assigned to (-)-glutethimide, the S-configuration could be given to (-)-aminoglutethimide, and therefore, the R-configuration can be assigned to (+)-aminoglutethimide, the enantiomer which inhibits steroid synthesis.