普瑞巴林的合成

Synthesis of Pregabalin

异戊醛经Knoevenagel缩合、Michael加成、水解脱羧得3-异丁基戊二酸,与尿素酰亚胺化反应得3-异丁基戊二酰亚胺,再经Hofmann重排得3-(氨甲基)-5-甲基己酸,用(S)-(+)-扁桃酸拆分得普瑞巴林,总收率为33%。

Pregabalin was synthesized with 33 % overall yield, from isovaleraldehyde by Knoevenagel condensation, Michael addition and hydrolysis to give 3-isobutylglutaric acid, which was subjected to imidization with urea followed by Hofmann rearrangement to afford 3-aminomethyl-5-methylhexanoic acid which was resolved with （S） mandelic acid.