Application of Transition-Metal Catalysis, Biocatalysis, and Flow Chemistry as State-of-the-Art Technologies in the Synthesis of LCZ696
Xingxian Gu, Jibin Zhao, Like Chen, Yunzhong Li, Bo Yu, Xiangguang Tian, Zhongcheng Min, Su Xu, Huijuan Gu, Junjie Sun, Xiaoquan Lu, Meng Chang, Xu‐Fan Wang, Liqun Zhao, Shengqing Ye, Hongwei Yang, Yingtao Tian, Feng Gao, Yu Gai, Guanghua Jia, Jingjing Wu, Yan Wang, Jianghua Zhang, Xuesong Zhang, Weichun Liu, Xin Gu, Xi Luo, Hai Dong, Huaimin Wang, Berthold Schenkel, Francesco Venturoni, Paolo Filipponi, Bertrand Guélat, Thomas Allmendinger, Bernhard Wietfeld, Pascale Hoehn, Nikola Kovacic, Luca Hermann, Thierry Schlama, Thomas Ruch, Nadine Derrien, Philippe Piéchon, Florian Kleinbeck
Abstract
LCZ696 is a novel treatment for patients suffering from heart failure that combines the two active pharmaceutical ingredients sacubitril and valsartan in a single chemical compound. While valsartan is an established drug substance, a new manufacturing process suitable for large-scale commercial production had to be developed for sacubitril. The use of chemocatalysis, biocatalysis, and flow chemistry as state-of-the-art technologies allowed to efficiently build up the structure of sacubitril and achieve the defined performance targets.