School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, China; Collaborative Innovation Center of New of New Drug Research and Safety Evaluation, Zhengzhou 450001, China.
School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, China.
Steroids. 2019 Jun;146:99-103. doi: 10.1016/j.steroids.2019.03.013. Epub 2019 Apr 2.
A four-step route for the synthesis of 2-methoxyestradiol (5) starting from 17β-estradiol (1) has been achieved with a 51% overall yield. The key step was the ruthenium-catalyzed ortho-C(sp)-H bond hydroxylation of aryl carbamates. Using dimethyl carbamate as the directing group, [RuCl(p-cymene)] as the catalyst, PhI(OAc) as the oxidant and trifluoroacetate/trifluoroacetic anhydride (1:1) as the co-solvent, the hydroxyl group could be singly installed at the 2-position of 3-dimethylcarbamoyloxyestradiol (2) with 65% yield. Subsequent methylation of hydroxy and removal of dimethyl carbamate afforded 2-methoxyestradiol (5).
以 17β-雌二醇（1）为起始原料，经四步反应以 51%的总收率合成了 2-甲氧基雌二醇（5）。关键步骤是芳基氨基甲酸酯的钌催化邻-C（sp）-H 键羟化。使用二甲基氨基甲酸酯作为导向基团，[RuCl(p-cymene)]作为催化剂，PhI(OAc)作为氧化剂，三氟乙酸/三氟乙酸酐（1:1）作为共溶剂，可将羟基单取代到 3-二甲基氨基甲酰氧基雌二醇（2）的 2-位，收率为 65%。随后对羟基进行甲基化，再脱去二甲基氨基甲酸酯，得到 2-甲氧基雌二醇（5）。
