A series of 3α-hydroxyl-3β-methoxymethyl-5α-pregnan-20-ones 7-15 possessing C-21 hydrophilic substituents were synthesized from the corresponding C21-bromo steroid 6 in 24%-89% yields. The hydrophilic groups include amino group from Delepine reaction, hydroxyl group from the hydrolysis by cesium formate in anhydrous MeOH, and amino acids, hydrazinecarboxamide, piperazine, and imidazolyl from nucleophilic substitution. Acylation and O-glycosylation of the resulting C-21 hydroxylsteroid also afforded the corresponding acylated and glycosylated products in excellent yield (77%-89%). Among the compounds, aminosteroid 7 and piperazinyl steroid 14 were most potent against the proliferation of human prostate cancer PC-3 cells with IC50 values of 42 and 82 μmol L−1, respectively.

中文翻译：

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具有 C-21 亲水取代基的 3α-羟基-3β-甲氧基甲基-5α-孕-20-one 的合成及抗增殖活性

从相应的 C21-溴类固醇 6 以 24%-89% 的产率合成了一系列具有 C-21 亲水取代基的 3α-羟基-3β-甲氧基甲基-5α-孕-20-酮 7-15。亲水基团包括来自Delepine反应的氨基，由甲酸铯在无水MeOH中水解产生的羟基，以及来自亲核取代的氨基酸、肼甲酰胺、哌嗪和咪唑基。所得 C-21 羟基类固醇的酰化和 O-糖基化也以优异的产率 (77%-89%) 提供相应的酰化和糖基化产物。在这些化合物中，氨基类固醇 7 和哌嗪基类固醇 14 对人前列腺癌 PC-3 细胞的增殖最有效，IC50 值分别为 42 和 82 μmol L-1。