Scholarlink

<p>Flow chemistry has many advantages over batch synthesis of organic small-molecules in terms of environmental compatibility, safety and synthetic efficiency when scale-up is considered. Herein, we report the 10-step chemo-biocatalytic continuous flow asymmetric synthesis of cyproterone acetate (<b>4</b>) in which 10 transformations are combined into a telescoped flow linear sequence from commercially available 4-androstene-3, 17-dione (<b>11</b>). This integrated one-flow synthesis features an engineered 3-ketosteroid-Δ<sup>1</sup>-dehydrogenase (ReM2)-catalyzed Δ<sup>1</sup>-dehydrogenation to form the C1, C2-double bond of A ring, a substrate-controlled Co-catalyzed Mukaiyama hydration of <b>9</b> to forge the crucial chiral C17<i>α</i>-OH group of D ring with excellent stereoselectivity, and a rapid flow Corey-Chaykovsky cyclopropanation of <b>7</b> to build the cyclopropyl core of A ring. By strategic use of these three key reactions and fully continuous-flow operations, cyproterone acetate (<b>4</b>) is produced in an overall yield of 9.6% in 3 h of total reaction time, this is the highest total number of chemical transformation performance in any other continuous-flow synthesis reported to date.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Flow chemistry-enabled asymmetric synthesis of cyproterone acetate in a chemo-biocatalytic approach

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月27日

查看全文
  • Yajiao Zhang,
  • Minjie Liu,
  • Xianjing Zheng,
  • Liang Gao,
  • Li Wan,
  • Dang Cheng,
  • Fener Chen

摘要

Flow chemistry has many advantages over batch synthesis of organic small-molecules in terms of environmental compatibility, safety and synthetic efficiency when scale-up is considered. Herein, we report the 10-step chemo-biocatalytic continuous flow asymmetric synthesis of cyproterone acetate (4) in which 10 transformations are combined into a telescoped flow linear sequence from commercially available 4-androstene-3, 17-dione (11). This integrated one-flow synthesis features an engineered 3-ketosteroid-Δ1-dehydrogenase (ReM2)-catalyzed Δ1-dehydrogenation to form the C1, C2-double bond of A ring, a substrate-controlled Co-catalyzed Mukaiyama hydration of 9 to forge the crucial chiral C17α-OH group of D ring with excellent stereoselectivity, and a rapid flow Corey-Chaykovsky cyclopropanation of 7 to build the cyclopropyl core of A ring. By strategic use of these three key reactions and fully continuous-flow operations, cyproterone acetate (4) is produced in an overall yield of 9.6% in 3 h of total reaction time, this is the highest total number of chemical transformation performance in any other continuous-flow synthesis reported to date.