Combining Incompatible Processes for Deracemization of a Praziquantel Derivative under Flow Conditions,Angewandte Chemie International Edition

当前位置： X-MOL 学术 › Angew. Chem. Int. Ed. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Combining Incompatible Processes for Deracemization of a Praziquantel Derivative under Flow Conditions
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2020-11-26 , DOI: 10.1002/anie.202013502
Giulio Valenti ₁ , Paul Tinnemans ₂ , Iaroslav Baglai ₃ , Willem L. Noorduin _{3,

4} , Bernard Kaptein ₅ , Michel Leeman ₁ , Joop H. ter Horst ₆ , Richard M. Kellogg ₁

Affiliation

An efficient deracemization method for conversion of the racemate to the desirable (R)‐enantiomer of Praziquantel has been developed by coupling incompatible racemization and crystallization processes. By a library approach, a derivative that crystallizes as a conglomerate has been identified. Racemization occurs via reversible hydrogenation over a palladium on carbon (Pd/C) packed column at 130 °C, whereas deracemization is achieved by alternating crystal growth/dissolution steps with temperature cycling between 5–15 °C. These incompatible processes are combined by means of a flow system resulting in complete deracemization of the solid phase to the desired (R)‐enantiomer (98 % ee). Such an unprecedented deracemization by a decoupled crystallization/racemization approach can readily be turned into a practical process and opens new opportunities for the development of essential enantiomerically pure building blocks that require harsh methods for racemization.

中文翻译：

组合不相容过程在流动条件下对吡喹酮衍生物进行脱硝

通过将不相容的外消旋作用和结晶过程结合起来，已经开发出一种有效的消旋方法，可将外消旋物转化为吡喹酮的所需（R）-对映体。通过文库方法，已经鉴定出结晶为团块的衍生物。外消旋作用是通过在130°C的钯/碳（Pd / C）填充柱上进行可逆氢化而实现的，而消旋作用是通过交替进行晶体生长/溶解步骤以及在5–15°C之间的温度循环实现的。这些不相容的过程通过流动系统结合在一起，导致固相完全脱硝为所需的（R）-对映体（98％ee）。通过分离的结晶/消解方法进行的这种空前的消硝化，可以很容易地转化为实际的过程，并为开发要求严格的消旋方法的对映体纯的基本结构单元提供了新的机会。

更新日期：2020-11-26

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11