Li S, Parish E J, Rodriguez-Valenzuela C, Brodie A M
Department of Chemistry, Auburn University, AL 36849-5312, USA.
Bioorg Med Chem. 1998 Sep;6(9):1525-9. doi: 10.1016/s0968-0896(98)00097-2.
A novel class of steroidal A/B ring isoxazoles have been prepared by two independent reaction schemes using 3 beta,17 beta-diacetoxyandrost-5-ene (1) and 3 beta,17 beta-diacetoxyandrost-4-en-6-one (4) as synthetic precursors. The key common intermediate in these syntheses, 3 beta,17 beta-diacetoxyandrost-4-eno[6,5,4-c,d] isoxazole (3), was prepared by synthetic methods described in both schemes. Further chemical modification of 3 yielded 3 beta,17 beta-dihydroxyandrost-4-eno[6,5,4-c,d] isoxazole (6), androst-3,17-dione-4-eno[6,5,4-c,d] isoxazole (7), and 17 beta-hydroxyandrost-3-one-4-eno[6,5,4-c,d] isoxazole (9). Human placental estrogen synthase (aromatase) bioassays were conducted to obtain the following IC50 values resulting from a 50% reduction of enzymatic activity: 6, 120.5 microM; 7, 1.889 microM. 9, 18.57 microM.
通过两个独立的反应方案，以3β,17β - 二乙酰氧基雄甾 - 5 - 烯（1）和3β,17β - 二乙酰氧基雄甾 - 4 - 烯 - 6 - 酮（4）作为合成前体，制备了一类新型的甾体A/B环异恶唑。这些合成中的关键共同中间体，3β,17β - 二乙酰氧基雄甾 - 4 - 烯并[6,5,4 - c,d]异恶唑（3），是通过两个方案中描述的合成方法制备的。对3进行进一步的化学修饰得到了3β,17β - 二羟基雄甾 - 4 - 烯并[6,5,4 - c,d]异恶唑（6）、雄甾 - 3,17 - 二酮 - 4 - 烯并[6,5,4 - c,d]异恶唑（7）和17β - 羟基雄甾 - 3 - 酮 - 4 - 烯并[6,5,4 - c,d]异恶唑（9）。进行了人胎盘雌激素合成酶（芳香化酶）生物测定，以获得因酶活性降低50%而产生的以下IC50值：6为120.5微摩尔；7为1.889微摩尔；9为18.57微摩尔。
