Methodological Research In The Total Synthesis Of BCD Ring Of Steroidal Key Skeleton

Steroidal compounds, such as estrogen, testosterone, progesterone and epinephrine,are important hormonal medicines, revealing strong biological activity. They are widedistribution but low content in the nature, and almost fail to meet the normal need ofhuman being in therapy. Some steroidal compounds, like the Norgestrel, do not exist innature，while the single way to afford them is total synthesis. So, total synthesis of steroidsas another key resource to afford steroidal compounds，has become the hot field ofMedicine Chemistry and Organic Chemistry.In this article, the synthesis of BCD ring of steroidal parent nucleus was researchedfrom the point of methodology. Because the specific configuration of natural steroids, weprepared optical CD ring fragment1H-inden-5-one-4-ene as starting material to avoid theuneconomical chiral resolution in the later phase of synthesis. It meant a definitiveasymmetry center was inducted in the early phase of synthesis. And then, in the case of thehydroxyl of CD ring fragment1H-inden-5-one-4-ene was unprotected, its4-position wasdirectly alkylated by using basic catalyst to afford a series of steroidal derivatives of CDring fragment. After the hydrogenation using Pd/C as catalyst, the double bond wasreduced successfully. When those problems about configuration faced in the closing B ringunder acid or basic surroundings were researched systematically, the steroidal BCD ringfragment with natural configuration was finally obtained. Furthermore, we certified theconfiguration of the steroidal BCD ring fragment through crystal diffraction.Actually, in this research process, we also tried to synthesize CD ring fragment byother schemes, and to separate its raceme in chemical way. In the alkylation of4-positionof CD ring fragment-1H-inden-5-one-4-ene, other schemes, such as the one-pot scheme ofsimilar Mannich reaction and the enamine scheme, were also attempted. Meantime,Uniform Design was used to optimize its alkylation conditions with t-BuOK as basiccatalyst. These entire attempts afford some useful enlightenment in the total synthesis ofsteroids.