Studies On The Steroidal D-ring Modification With Important Physiological Activities

In recent years, with the deepening research and development of the pharmaceuticals, more and more natural products and synthetic products with important physiological activities have been used for clinical medicines. Steroidal compounds are a kind of natural products that have important physiological activities. A lot of natural and synthetic steroids have anti-inflammatory,antitumor, anti-aging and other pharmacological effects that have widely used in the treatment of skin diseases, cancer, cardiovascular diseases and so on. The researches have shown that a certain position of the natural steroidal compounds was modified which can make their physiological activities become much higher than the original steroidal compounds. Therefore,based on natural steroid compounds, the modifications of the structures have drawn a lot of attention. They have become an important area of the researches and developments of new drugs.In this paper a series of new steroidal derivatives were synthesized by modifying steroid D-ring in different location.1. Dehydroepiandrosterone (DHEA) was used as a starting material, the esterification of DHEA with acetic anhydride in the presence of pyridine gave 3β-acetoxylandrost-5-ene-17-one.The following sulfonylation of 3β-acetoxylandrost-5-ene-17-one with trifluoromethanesulfonic anhydride afforded a 17-trifuoromethanesulfonyl steroid. Suzuki coupling reaction of 17-trifluoro-methanesulfonyl steroid and boronic acid reagents was carried out in the presence of Ni(PCy3)2Cl2. Finally,we acquired eight different steroid compounds. All compounds were characterized by IR, NMR, and HRMS spectroscopy.2. The epiandrosterone (EPI) was used as a starting material, (3β)-1 6-bromo-3-hydroxy-17-one was got via the bromination reaction using CuBr2, and then using DMF as solvent and under refluxing, the elimination of hydrogen bromide was carried out in the presence of Li2CO3 and LiBr to give (3β)-3-hydroxy-14(15)-ene-17-one and (3β)-3-hydroxy-8(14),15(16)-diene-17- one.Following, iodine was introduced at 16-position of steroid using CCl4/I2/pyridine system. Then,the Suzuki coupling of iodosteroid and some ArB(OH)2 in the presence of palladium catalyst afforded eight (3 β)-16-aryl-3-hydroxy androst-8(14), 15(16)-diene-17-ones. Sonogashira coupling reaction gave three compounds. Finally, five single crystals were gotten. All compounds were characterized by NMR, IR, and HRMS spectroscopy. The single crystal structure of the target compound which we obtained was confirmed by X-ray diffraction method.3. As a starting material, EPI was transftered into (3β)-3-hydroxy-14(15)-ene-17-one via two steps. The epoxidation of 3β)-3-hydroxy-14(15)-ene-17-one was carried out using MMPP as the oxidant in acetone as solvent to give (3 β)-3-hydroxy-14α, 15α-epoxysteroid-17-one. On the one hand, the ring opening of (3 β)-3 -hydroxy-14α, 15α-epoxysteroid-17-one gave sterol compounds 3β, 14β-dihydroxy androstane-17-one under acid condition, on the other hand, the nuclophilic addition of 14α,15α-epoxysteroid with arylamine and ring opening of the epoxide afforded 3β,15α-dihydroxy-14β-arylamine androstane-17-one.Additionally, 3α-hydroxyandrostane-17-one was used as a starting material, 3α-hydroxy androstane-14-ene-17-one and 3α-hydroxy-14β-androstane-15-ene-17-one were prepared via two steps, the transformation path of products and mechanism of the title reaction also was investigated. All compounds were characterized by NMR,IR,and HRMS spectroscopy. The single crystal structures of four target compounds were confirmed by X-ray diffraction method.