Synthesis Of 7α-hydroxy DHEA, 5α-androst-16-en-3-one And 4-hydroxyandrostene Steroids

This dissertation comprises three parts. 1. Synthesis of â–³⁵-androsten-3 β ,7α-diol-17-one (7α-hydroxy DHEA)The â–³⁵-androsten-3β,7α-diol-l7-one (7α-hydroxy DHEA) was synthesized by two routes:Using DHEA acetate as staring material, 7α-hydroxy DHEA was prepared with total yield of 40% by four steps including bromination, isomerization, esterification and hydrolysis. The process has been brought about industrialization.Reaction of DHEA acetate with PhCO₃Bu-t in the presence of cuprous bromide could introduce directly an acyloxy group at C-7 alpha position, and then gave 7α-hydroxy DHEA by hydrolysis. Te reaction conditions were optimized, and the acyloxylation yield was improved from 11.7% to 34%. 2. Synthesis of 5α-androst-16-en-3-one (androstenone)5α-Androst-16-en-3-one (androstenone) which has an intense musky is used as a pheromone in cosmetic. Androstenone was prepared from commercially available epiandrosterone by four-step. Reaction of epiandrosterone with hydrazine hydrate gave 3β-hydroxy-5α-androstan-17-one hydrazone, and the hydrazone was converted into 17β-iodo-5α-androst-16-en-3β-ol with iodine. The removal of iodine atom by reduction with Na in boiling ethanol gave 5α-androst-16-en-3β-ol. The final oxidation of the 3-alcohol to ketone was carried out with IBX as oxidant. This procedure has been optimized. The total yield was improved from 34% to 80%. IBX was used avoiding chromium reagent, which made the process environmental benign and the product purification convenient. 3. Preparation of 4-hydroxyandrostene steroids4-Hydroxytestosterone is used as a protein anabolic hormone for treating with the disease of protein metabolize and endocrine system. 4-Hydroxy-androst-4-ene-3,17-dione (Formestane) may be used as an inhibitor ofthe biosynthesis of estrogens, and is effective treating with breast cancer. 4-Hydroxytestosterone and Formestane were prepared from testosterone and androst-4-ene-3,17-dione via epoxidation, chloration, base catalytic hydrolysis, with the yield of 50% and 40%, respectively.