Departments of Chemistry and Molecular Biosciences, Chemistry of Life Processes Institute, Center for Molecular Innovation and Drug Discovery, and Center for Developmental Therapeutics , Northwestern University , Evanston , Illinois 60208 , United States.
Org Lett. 2018 Aug 3;20(15):4589-4592. doi: 10.1021/acs.orglett.8b01872. Epub 2018 Jul 16.
( S)-3-Amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (OV329, 1) is being developed for the treatment of epilepsy and addiction. The previous 14-step synthesis of OV329 was low yielding, involved an unselective α-elimination to form the cyclopentene, required the use of tert-butyllithium, and produced toxic selenium byproducts in the penultimate step. A new synthesis, which avoids the aforementioned issues, was carried out on large scale, reducing the step count from 14 to 9 steps and increasing the overall yield from 3.7% to 8.1%.
（S）-3-氨基-4-（二氟亚甲基）环戊-1-烯-1-羧酸（OV329，1）正在开发用于治疗癫痫和成瘾。之前的 OV329 合成需要 14 步，产率低，涉及非选择性的α消除以形成环戊烯，需要使用叔丁基锂，并在倒数第二步产生有毒的硒副产物。一种新的合成方法避免了上述问题，可以大规模进行，将步骤数从 14 步减少到 9 步，总收率从 3.7%提高到 8.1%。
