(3S)-1-[(R)-2-羟基-1-苯乙基]-3-甲基-2-哌啶酮的合成（英文）

被引：0

作者：

Xiaozhong WANG ^{[1
]}

Xia WANG ^{[1
]}

Yingqi CHEN ^{[1
]}

Liyan DAI ^{[1
]}

Xingcong LI ^{[2
]}

机构：

[1] College of Chemical and Biological Engineering, Zhejiang University

[2] National Centers for Natural Products Research, Research Institute of Pharmaceutical Sciences, The University of

来源：

Journal of Zhejiang University-Science A(Applied Physics & Engineering) | 2016年 / 02期

关键词：

哌啶酮; 生物碱; 不对称合成; D-苯甘氨醇; 醇羟基保护基;

D O I：

暂无

中图分类号：

O621.3 [有机合成化学];

学科分类号：

摘要：

目的:探索合成(3S)-1-[(R)-2-羟基-1-苯乙基]-3-甲基-2-哌啶酮的新方法。创新点:以常规化工原料D-苯苷氨醇为主要原料,在比较温和的条件下合成重要的药物中间体(3S)-1-[(R)-2-羟基-1-苯乙基]-3-甲基-2-哌啶酮及其同系物。该方法中的甲基化步骤较常规甲基化步骤减少1当量s-Bu Li的用量,更环保和安全。方法:利用D-苯苷氨醇的空间位阻作用,在六元环内酰胺中引入具有特定光学纯度的手性甲基。在甲基化过程中,用叔丁基二甲基氯硅烷对羟基进行保护,以减少仲丁基锂的用量。结论:以工业易得的δ-戊内酯及D-苯苷氨醇为初始原料,探索合成3-甲基-2-哌啶酮类物质的新方法。新方法中对仲丁基锂的消耗量与常规方法有所不同。当羟基受保护时,甲基化1当量六元环内酰胺(化合物7)消耗1.5当量而非2.5当量仲丁基锂,甲基化产物脱掉醇羟基保护基,得到(3S)-1-[(R)-2-羟基-1-苯乙基]-3-甲基-2-哌啶酮(化合物1)及其非对映异构体(3R)-1-[(R)-2-羟基-1-苯乙基]-3-甲基-2-哌啶酮(化合物8),二者摩尔比为1:2.5。通过重结晶或柱层析的方法可对二者进行完全分离。

引用

页码：163 / 170

页数：8

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