Enamine Ltd./Bienta, Chervonotkatska 78, 02094, Kyiv, Ukraine.
Taras Shevchenko National, University of Kyiv, Chemistry Department, Volodymyrska 64, 01601, Kyiv, Ukraine.
Chemistry. 2018 Apr 11;24(21):5444-5449. doi: 10.1002/chem.201800193. Epub 2018 Feb 15.
The synthesis of multifunctional spirocycles was achieved from common cyclic carboxylic acids (cyclobutane carboxylate, cyclopentane carboxylate, l-proline, etc.). The whole sequence included only two chemical steps-synthesis of azetidinones, and reduction into azetidines. The obtained spirocyclic amino acids were incorporated into a structure of the known anesthetic drug Bupivacaine. The obtained analogues were more active and less toxic than the original drug. We believe that this discovery will lead to a wide use of spirocyclic building blocks in drug discovery in the near future.
多功能螺环化合物的合成就可以从常见的环状羧酸（环丁烷羧酸、环戊烷羧酸、L-脯氨酸等）中实现。整个过程仅包含两步化学反应——氮杂环丁酮的合成和还原成氮杂环丁烷。所得到的螺环氨基酸被整合到已知麻醉药物布比卡因的结构中。得到的类似物比原药活性更高，毒性更小。我们相信，这一发现将导致在不久的将来在药物发现中广泛使用螺环砌块。
