SYNTHESIS AND PHARMACOLOGICAL EFFECTS OF BUTADIENE AND CYCLOPENTADIENE ADDUCTS OF METHANDROSTENOLONE IN RATS

Abstract

In this study the reactivity of methandrostenolone or [(17b)-17-hydroxy-17-methylandrosta-1, 4-diene-3-one], as a dienophil in a Diels-Alder type cycloaddition reaction was investigated. The purpose of this approach was to investigate whether the 1-dehydro position of methandrostenolone 1 undergoes a cycloaddition reaction with dienes, such as 1, 3 butadiene or cyclopentadiene, and to investigate the biological behavior of the reaction adducts, i.e, compound 3 {(17b)-17-hydroxy-17-methyl androsta [1a, 2a] cyclohex 3’, 4-diene-3-one} and compound 4 {(17b)-17-hydroxy-17-methyl androsta [1a, 2a] cyclohex (2’,5’ methylene) 3’, 4-diene-3-one}, relative to compound 1. The results indicated that thedDiels-Alder reactionddid notpproceed under the usual circumstances of high pressure and temperature, but could proceed in the presence of a Lewis acid (AlCl3). The structures of compounds 3 and 4 were confirmed by spectroscopic methods. The androgenic behavior of compounds 3 and 4 in comparison to compound 1 in the apomorphine test indicated that both compounds were almost devoid of androgenic activity, but prevented apomorphine mediated penile erection in male rats in a similar manner as cyproterone acetate.