简捷有效合成多肽渗透促进剂前体8-氨基辛酸的新方法
Concise and Effective New Syntheses of 8-Aminooctanoic Acid,a Precursor of Polypeptide Osmotic Accelerator
罗忠华 1区锦旺 2孙国栋 3张杨 2张霁3
作者信息
- 1. 广东东阳光药业抗感染新药研发国家重点实验室,广东东莞 523871;湖北宜昌东阳光制药有限公司,湖北宜昌 443300
- 2. 湖北宜昌东阳光制药有限公司,湖北宜昌 443300
- 3. 广东东阳光药业抗感染新药研发国家重点实验室,广东东莞 523871
- 折叠
摘要
以己二酸单甲酯(2)作为起始原料,经酰氯化、Nenitzescu反应得6-氧代-8-氯辛酸甲酯(4),4经取代、缩合得(E)-8-(1,3-二氧代异吲哚啉-2-基)-6-(2-甲苯磺酰肼亚基)辛酸甲酯(6),6经过还原、肼解及水解反应,得8-氨基辛酸(1),该化合物是合成渗透增强剂N-[8-(2-羟基苯甲酰基)-氨基]辛酸钠(SNAC)的重要起始物.1的新合成路线总收率为58.9％(以2计),纯度99.83％.该工艺条件温和,原料经济易得,操作简单,具有良好的产业化前景.
Abstract
Methyl 8-chloro-6-oxooctanoate(4)was synthesized by acylating chlorination and Nenitzescu reaction from the commercial available material 6-methoxy-6-oxohexanoic acid(2).Then methyl(E)-8-(1,3-dioxoisoindolin-2-yl)-6-(2-tosylhydrazineylidene)octanoate(6)was obtained by substitution and condensation of 4.Ultimately,8-aminooctanoic acid(1)was obtained by reduction,hydrazolysis and hydrolysis reaction from 6,which was an important starting material for the synthesis of the permeation enhancer sodium N-[8-(2-hydroxybenzoyl)amino]octanoate(SNAC).The total yield of this new synthetic route was 58.9％(based on 2)with the purity of 99.83％.This new process is suitable for industrial production with mild conditions,low raw material cost and simple operations.
关键词
N-[8-(2-羟基苯甲酰基)-氨基]辛酸钠/8-氨基辛酸/合成Key words
sodium N-[8-(2-hydroxybenzoyl)amino]octanoate/8-aminooctanoic acid/synthesis引用本文复制引用
基金项目
广东省抗病毒药物研发企业重点实验室项目(2020B1212070003)
出版年
2024
NETL
NSTL
万方数据