He Yongqi, Leng Xin-Yu, Wang Runying, Sun Lulu, Zhang Dan, Yang Yushe
School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Mol Divers. 2025 Mar 16. doi: 10.1007/s11030-025-11154-1.
In previous studies, we discovered YZD-7082B, a selective estrogen receptor degrader (SERD) with excellent comprehensive properties. Here, we reported the development of an efficient multigram-scale synthetic process for YZD-7082 in 13 steps. The route featured a chiral resolution of a thiochroman intermediate with a unique cis-1,2-diaryl motif using a chiral amine and a mild reduction of amide using ZnEt/LiCl/(EtO)SiH system. This approach also overcomes the issues of high loadings of palladium catalysts and long reaction time. The developed process provided YZD-7082B with an HPLC purity of > 99.8% and ee of > 99%.
在先前的研究中，我们发现了YZD-7082B，一种具有优异综合性能的选择性雌激素受体降解剂（SERD）。在此，我们报道了一种高效的、以13步合成YZD-7082的多克级规模合成工艺。该路线的特点是使用手性胺对具有独特顺式-1,2-二芳基基序的硫代色满中间体进行手性拆分，并使用ZnEt/LiCl/(EtO)SiH体系对酰胺进行温和还原。这种方法还克服了钯催化剂高负载量和反应时间长的问题。所开发的工艺使YZD-7082B的HPLC纯度>99.8%，对映体过量值（ee）>99%。
