文章基本信息

标题：Direct N1-Selective Alkylation of Hydantoins Using Potassium Bases
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作者：Yumi Shintani ; Koichi Kato ; Masashi Kawami 等
期刊名称：Chemical and Pharmaceutical Bulletin
印刷版ISSN：0009-2363
电子版ISSN：1347-5223
出版年度：2021
卷号：69
期号：4
页码：407-410
DOI：10.1248/cpb.c20-00857
出版社：The Pharmaceutical Society of Japan
摘要：Hydantoins, including the antiepileptic drug phenytoin, contain an amide nitrogen and an imide nitrogen, both of which can be alkylated. However, due to the higher acidity of its proton, N 3 can be more easily alkylated than N 1 under basic conditions. In this study, we explored methods for direct N 1 -selective methylation of phenytoin and found that conditions using potassium bases [potassium tert -butoxide ( t BuOK) and potassium hexamethyldisilazide (KHMDS)] in tetrahydrofuran (THF) gave N 1 -monomethylated phenytoin in good yield. The applicable scope of this reaction system was found to include various hydantoins and alkyl halides. To explore the function of methylated hydantoins, the effects of a series of methylated phenytoins on P-glycoprotein were examined, but none of methylated products showed inhibitory activity toward rhodamine 123 efflux by P-glycoprotein.
关键词：methylation;regioselective;hydantoin;P-glycoprotein