Synthesis of 1, 2-t-testosterone and 1, 2, 5, 6-t-dihydrotestosterone by selective hydrogenation of testosterone acetate

Full text: Labeling of testosterone and dihydrotestosterone with tritium was necessary for carrying out of radiometric and molecular biology studies concerning androgen dependent diseases. Testosterone was labeled by selective hydrogenation of 1,2 dihydrotestosterone acetate, forerunner was synthesized in two steps: 1) esterification of testosterone using acetic anhydride, and 2) selective dehydrogenation with 2,6-dichloro-3,5-dicyan-1,4 quinone of the ester formed in the first step. Testosterone acetate was synthesized and purified with yields of 73%, and respectively 80%. The dehydrogenation process was characterized by yields of 82% for synthesis and 33% for purification. The tritium labeled hormones were obtained in two steps: 1) selective hydrogenation of Δ1- testosterone acetate in the presence of T2 gas, at low pressure, and 2) hydrolysis of the esther at basic pH. The raw labeled compounds were purified by preparative thin layer chromatography, using the system: silica gel GF 254 activated at 110 deg. C. for one hour and chloroform: acetone (9:1v/v) mixture as eluent. Radioactive concentration, radiochemical purity, chemical concentration and specific activities of labelled products was determined. Hydrogenation reaction was also analysed by quantum mechanical chemical methods. Total binding energies of reactants, transitional state and reaction products were determined. (author)