A directed synthesis of two progesterone metabolites, allopregnanolone and 3a-hydroxy-pregn-4-en-20-one, from Δ 16 -pregnanolone and progesterone, respectively, was carried out by a reduction of the carbonyl groups in positions 3 and subsequent inversion of the configuration of the resulting alcohols by the Mitsunobu reaction. The selectivity of the reduction of the conjugated carbonyl group in position 3 of progesterone with sodium borohydride in the presence of cerium(III) chloride (Luche reduction) was demonstrated. The ef ect of the obtained metabolites on the proliferation of breast cancer cells of the MCF-7 and T47D lines under normal and steroid-free conditions was studied. It is shown that the ef ect of these compounds on the proliferation depends on the presence of additional steroids in the culture medium. Metabolites exerted small cytostatic ef ects on the growth of the MCF-7 cells under standard conditions, while the transfer of the cells to a steroid-free medium weakened these cytotoxic ef ects. In the experiments with the T47D line cells, the cell growth was stimulated under both standard and steroid-free conditions. Allopregnanolone and progesterone stimulate the growth to a greater extent under steroid-free conditions than under standard ones.

中文翻译：

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选择性合成两种主要的孕酮代谢物 3α-羟基-5α-孕酮（allopregnanolone）和 3α-羟基孕酮-4-en-20-one，并评估它们对激素依赖性人乳腺癌细胞增殖的影响

通过还原 3 位羰基和随后的反转，分别从 Δ 16-孕烯醇酮和孕酮直接合成两种孕酮代谢物 allopregnanolone 和 3a-hydroxy-pregn-4-en-20-one通过 Mitsunobu 反应生成的醇的构型。证明了在氯化铈 (III) 存在下用硼氢化钠还原孕酮 3 位共轭羰基的选择性（Luche 还原）。研究了获得的代谢物在正常和无类固醇条件下对 MCF-7 和 T47D 系乳腺癌细胞增殖的影响。结果表明，这些化合物对增殖的影响取决于培养基中是否存在额外的类固醇。在标准条件下，代谢物对 MCF-7 细胞的生长产生小的细胞抑制作用，而将细胞转移到不含类固醇的培养基中会减弱这些细胞毒性作用。在 T47D 系细胞的实验中，在标准和无类固醇条件下刺激细胞生长。别孕酮和孕酮在无类固醇条件下比在标准条件下更大程度地刺激生长。