L-去氧肾上腺素合成研究进展

Research progress in the synthesis of L-phenylephrine

L-去氧肾上腺素是一种α1受体激动药物,具有血管收缩作用,在临床中应用广泛,并呈稳定的增长趋势。国内外对于合成L-去氧肾上腺素的报道较多,但多为专利且年代跨度大,缺乏系统的综述。本文综述了国内外合成L-去氧肾上腺素的各种工艺路线及最新研究成果,按拆分法和不对称合成法归类,对各合成方法的优缺点进行了评述。传统的拆分法随着消旋体合成工艺的革新、动态动力学拆分等新技术的应用,在L-去氧肾上腺素的生产中将继续发挥作用。化学不对称合成经过近三十年的研究,已成为制备L-去氧肾上腺素药物最经济、有效的合成手段,并保持良好的发展态势。生物不对称合成技术将逐步从实验室和基础研究步入到应用阶段,今后在L-去氧肾上腺素的合成中,将占有十分重要的地位。

L-phenylephrine is anα1 receptor agonist drug,with vasoconstriction,which is widely used in clinical practice,and its market demand shows a trend of steady growth. Some synthesis methods of L-phenylephrine were reported at home and abroad. However,most of these reports are patents and apart from each other,lack of systematic review. The paper is aimed to summarize various routes for the synthesis of L-phenylephrine and the latest research results,then divides them into two categories, split method and asymmetric synthesis. Both the advantages and disadvantages of each method are reviewed. The traditional split method will continue to play an important role in the production of L-phenylephrine with the racemic synthesis process innovation and the application of new technologies,such as dynamic kinetic resolution. Chemical asymmetric synthesis,after nearly 30 years of research,has been the most economical and effective mean to prepare L-phenylephrine drug,and maintains a good momentum of development. Biological asymmetric synthesis technology will develop gradually from the lab and basic research into application stage. It will occupy a very important position in the synthesis of L-phenylephrine in the future.