手性双哌啶氨基醇衍生物的合成

由简单的烷基胺与丙烯酸甲酯为原料,经Michael加成、Dieckmann环合、脱羧得到三种N-烷基-4-哌啶酮。这些N-烷基-4-哌啶酮分别与(R)-(-)-2-氨基-1-丁醇和多聚甲醛进行Mannich反应,再经黄鸣龙还原得到三种新的具有手性的双哌啶氨基醇衍生物。采用1H NMR、13C NMR、IR、MS对目标产物的结构进行了表征,并对其旋光度进行了测定。Mannich反应优化条件为:甲醇回流温度下反应,物料摩尔比为n(N-烷基-4-哌啶酮)∶n((R)-2-氨基-1-丁醇)∶n(多聚甲醛)=1∶1.2∶2.5。

Synthesis of Chiral Amino Alcohol Derivatives with Bispidine Moiety

Three N-alkyl-4-piperidones were synthesised through the Michael addition of alkyl amines and methyl acrylate and followed by Dieckmann cyclization and decarboxylation.The N-alkyl-4-piperidones reacted with(R)-(-)-2-amino-1-butanol and paraformaldehyde through Mannich reaction followed by HUANG Mi-lon reduction to afford three new chiral amino alcohol derivatives with bispidine moiety.The structures of the final products were characterized by ~1H NMR, ~13C NMR,IR and MS.Their optical rotation was also determined.The optimum reaction conditions of the Mannich reaction were as follows: reacting at reflux temperature of methanol and the mole ratio of n(N-alkyl-4-piperidone)∶n((R)-(-)-2-amino-1-butanol)∶n(paraformaldehyde)=1∶1.2∶2.5.