Zhou Dejun, Wang Keyang, Zhang Yuying, Liu Xiaoyue, Mao Xiaoxia
The key Laboratory of Chinese Medicine Research and Development in Hebei Province, Traditional Chinese Medicine Institute of Chengde Medical University, Chengde, 067000, China.
Shandong Daguan Pharmaceutical Technology Co Ltd, Jinan, Shandong, 250100, China.
Curr Org Synth. 2025;22(5):614-619. doi: 10.2174/0115701794344307241027093947.
Timolol maleate is clinically used for the treatment of hypertension, angina pectoris, tachycardia, and glaucoma.
The aim of this study was to enhance the safe use of timolol maleate and investigate a synthesis method for 3-S-timolol, a newly identified impurity in timolol API (Active Pharmaceutical Ingredients).
(S)-3-(tert-butylamino)propane-1,2-diol (1) was used as a raw material. 3-S-timolol maleate (7) was synthesized through a five-step reaction. Overall yield was 57.7%, with a purity of 98%.
The structure of the target compound was confirmed analysis of its H nuclear magnetic resonance, C nuclear magnetic resonance, and high-resolution mass spectrometry spectra.
The synthesis method was straightforward and yielded a high-purity product suitable for use as a reference in the analysis and identification of timolol maleate-related substances.
马来酸噻吗洛尔临床上用于治疗高血压、心绞痛、心动过速和青光眼。
本研究旨在提高马来酸噻吗洛尔的安全使用，并研究噻吗洛尔原料药（活性药物成分）中新鉴定出的杂质3 - S - 噻吗洛尔的合成方法。
以（S）-3 - （叔丁基氨基）丙烷 - 1,2 - 二醇（1）为原料。通过五步反应合成马来酸3 - S - 噻吗洛尔（7）。总收率为57.7%，纯度为98%。
通过对目标化合物的氢核磁共振、碳核磁共振和高分辨率质谱光谱分析，确认了其结构。
该合成方法简便，得到了高纯度产物，适用于作为马来酸噻吗洛尔相关物质分析和鉴定的对照品。
