The Modification Of 3,22-Position In Solamargine And Evalution Of Anticancer Activity

Based on the structure of Solamargine, a compound with reported exciting anti-tumor activity, a variety of steroid alkaloid compounds with potential activities in competing with tumor cells were designed with a purpose of identifying new anti-tumor drugs. The synthetic routes of target molecule were also studied.Starting from 16-dehydropregnenolone acetate, target compound A could be obtained by epoxy oxidation, protected by tert-butyldimethylsilyl chloride, Huang Minglong reduction to provide compound 4,3β-tert-Butyl-dimethylsilyaloxy-5,17(20E)-diene-pregna-16a-ol. Compound 4 was treated by MnO2 to provide 33β-tert-Butyl-dimethyl-silyloxy-5,17(20E)-diene-pregna-16-one, and then Michael addition with CH3NO2 to provide 3β-tert-Butyl-dimethylsilyloxy-pregna-5-en-16-one as compound 6, reducted by sodium borohydride to provide the key intermediate comound 7. (20S) 3β-tert-Butyl-dimethylsilyloxy-pregna-5-en-16-one, and then modified by Nef reaction, Mitsunobu reaction to form the target compound.The structures of the intermediates and products were comfired by'H NMR, (?)C NMK, IR. And specific conditions of some reactions are optimized to obtain high yield in reasonable reaction time. The stereochemistry and mechanism of some synthetic reaction was discussed.