Concise synthesis of 2-methoxyestradiol from 17β-estradiol through the C(sp2)-H hydroxylation

被引：4

作者：

Ba, Meng-Yu ^{[1
,2
]}

Xia, Li-Wen ^{[1
,2
]}

Li, Hong-Liang ^{[1
,2
]}

Wang, Ying-Ge ^{[1
,2
]}

Chu, Ya-Nan ^{[1
,2
]}

Zhao, Qing ^{[1
,2
]}

Hu, Chao-Ping ^{[1
,2
]}

He, Xiao-Tong ^{[1
,2
]}

Li, Tian-Xiao ^{[1
,2
]}

Liang, Kai-Yue ^{[1
,2
]}

Zhang, Ya-Han ^{[1
]}

Yang, Liu ^{[1
]}

Xie, Wen-Hao ^{[1
]}

Yang, Hua ^{[1
,2
]}

Sun, Mo-Ran ^{[1
,2
]}

机构：

[1] Zhengzhou Univ, Sch Pharmaceut Sci, Kexue Rd 100, Zhengzhou 450001, Henan, Peoples R China

[2] Collaborat Innovat Ctr New New Drug Res & Safety, Zhengzhou 450001, Henan, Peoples R China

来源：

STEROIDS | 2019年 / 146卷

基金：

中国国家自然科学基金;

关键词：

2-Methoxyestradiol; 17; beta-Estradiol; Ru-catalyst; C-H hydroxylation; METABOLITE;

D O I：

10.1016/j.steroids.2019.03.013

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A four-step route for the synthesis of 2-methoxyestradiol (5) starting from 17 beta-estradiol (1) has been achieved with a 51% overall yield. The key step was the ruthenium-catalyzed ortho-C(sp(2))-H bond hydroxylation of aryl carbamates. Using dimethyl carbamate as the directing group, [RuCl2(p-cymene)](2) as the catalyst, PhI(OAc)(2) 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).

引用

页码：99 / 103

页数：5

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