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手性催化制药在自制 3D 打印介观反应器中的活性成分的选择性合成。

Stereoselective Catalytic Synthesis of Active Pharmaceutical Ingredients in Homemade 3D-Printed Mesoreactors.

机构信息

Dipartimento di Chimica, Università degli Studi di Milano, Via C. Golgi, 19, 20133, Milano, Italy.

出版信息

Angew Chem Int Ed Engl. 2017 Apr 3;56(15):4290-4294. doi: 10.1002/anie.201612192. Epub 2017 Mar 27.

Abstract

3D-printed flow reactors were designed, fabricated from different materials (PLA, HIPS, nylon), and used for a catalytic stereoselective Henry reaction. The use of readily prepared and tunable 3D-printed reactors enabled the rapid screening of devices with different sizes, shapes, and channel dimensions, aimed at the identification of the best-performing reactor setup. The optimized process afforded the products in high yields, moderate diastereoselectivity, and up to 90 % ee. The method was applied to the continuous-flow synthesis of biologically active chiral 1,2-amino alcohols (norephedrine, metaraminol, and methoxamine) through a two-step sequence combining the nitroaldol reaction with a hydrogenation. To highlight potential industrial applications of this method, a multistep continuous synthesis of norephedrine has been realized. The product was isolated without any intermediate purifications or solvent switches.

摘要

3D 打印流反应器采用不同材料(PLA、HIPS、尼龙)设计和制造,并用于催化立体选择性 Henry 反应。使用易于制备和可调的 3D 打印反应器可以快速筛选具有不同尺寸、形状和通道尺寸的设备,旨在确定性能最佳的反应器设置。优化后的工艺以高产率、中等非对映选择性和高达 90%的对映体过量值提供产物。该方法通过将硝醛缩合反应与氢化反应相结合,应用于生物活性手性 1,2-氨基醇(去甲麻黄碱、间羟胺和甲氧基胺)的连续流合成。为了突出该方法的潜在工业应用,实现了去甲麻黄碱的多步连续合成。产物无需任何中间纯化或溶剂切换即可分离。

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