Janssen R&D , API Small Molecule Development, Discovery Product Development & Supply , Hochstrasse 201 , 8205 Schaffhausen , Switzerland.
Porton (Shanghai) R&D Center , 1299 Ziyue Road, Zizhu Science Park, Minhang District , Shanghai 200241 , China.
Org Lett. 2019 Aug 16;21(16):6575-6578. doi: 10.1021/acs.orglett.9b02575. Epub 2019 Aug 8.
An efficient asymmetric synthesis of ()-ketamine (esketamine) based on catalytic enantioselective transfer hydrogenation of cyclic enone and [3,3]-sigmatropic rearrangement of allylic cyanate to isocyanate is described. The catalytic asymmetric route afforded esketamine (99.9% ee) in 50% overall yield over four steps and forms the basis for the future development of the drug substance. Furthermore, the route was applicable to the synthesis of ()-norketamine via simple hydrolysis of isocyanate penultimate.
本文描述了一种基于环状烯酮的催化对映选择性转移氢化和烯丙基氰酸酯的[3,3]-σ重排生成异氰酸酯的高效不对称合成（）-ketamine（esketamine）（-氯胺酮）的方法。该催化不对称路线以 4 步总收率 50%的产率提供了 esketamine（99.9%ee），为药物物质的未来发展奠定了基础。此外，该路线适用于通过异氰酸酯前体的简单水解合成（）-norketamine。
