摘要
以3-环己基-L-丙氨酸、Boc-L-天冬氨酸-4-苄酯为原料合成二肽L-天冬氨酰-3-环己基-L-丙氨酸-1-甲酯(Ⅰ),以3-羟基-4-甲氧基苯甲醛为原料经过Witting反应、H2还原和DIBAL-H还原三步反应合成3-羟基-4-甲氧基苯丙醛(Ⅱ),然后Ⅰ与Ⅱ在氢气、Pd/C催化作用下进行还原氨化反应,得到目标产物N-[3-(3-羟基-4-甲氧基苯基)丙基]-α-L-天冬氨酰-3-环己基-L-丙氨酸-1-甲酯(Ⅲ),总产率为47%。产物的结构采用IR、1HNMR、13CNMR和HRMS进行表征,并验证其甜度约为蔗糖的25000倍。合成终产物的最佳工艺条件为:n(Ⅱ)∶n(Ⅰ)=1∶1,Pd/C催化剂用量为反应物总重的10%,体积分数80%的甲醇水溶液为溶剂,反应温度35℃,反应时间20 h。
The dipeptide sweetener, N-[3-(3-hydroxy-4-methoxyphenyl)propyl]-α-L-aspartyl-β-cyclohexyl-Lalanine-1-methylester(Ⅲ) was synthesized from 3-(3-hydroxy-4-methoxyphenyl)propanal(Ⅱ) and dipeptide(Ⅰ) via a reductive amination reaction in the presence of a catalytic amount of palladium-carbon under hydrogen. The total yield was 47%. Compound Ⅱ was prepared from 3-hydroxy-4-methoxybenzaldehyde by Witting reaction, followed by hydrogenation and DIBAL-H reduction. The dipeptide(Ⅰ) was synthesized via a condensation between 3-cyclohexyl-L-alanine and Boc-L-aspartic acid-4-benzyl ester. The structure of product(Ⅲ) was confirmed by IR, 1 HNMR, 13 CNMR and HRMS techniques. It was 25000 times sweeter than sucrose. The optimum reaction conditions for the synthesis of product(Ⅲ) were determined as follows: n(Ⅱ)∶n(Ⅰ)=1∶1, the amount of Pd/C catalyst being 10% of the total weight of reactants, 80%(volume fraction) methanol as solvent, reaction temperature 40 ℃, and reaction time 20 h.
作者
邱云
胡南
穆小青
谭奇坤
胡晶
晏日安
QIU Yun;HU Nan;MU Xiao-qing;TAN Qi-kun;HU Jing;YAN Ri-an(Department of Food Science and Engineering,Jinan University,Guangzhou 510000,Guangdong,China)
出处
《精细化工》
EI
CAS
CSCD
北大核心
2019年第6期1144-1148,1158,共6页
Fine Chemicals
基金
广东省科技计划项目(2016B020204002)~~
