N-烷基酰胺类衍生物的质谱裂解机制研究
Fragmentation Pathways and Patterns of N-Alkylamides Derivatives
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摘要: 以阿纳其根中的N-烷基类化合物（NAAs）为先导化合物，以对羟基苯乙胺和系列脂肪酸为原料，HATU为缩合剂，合成了N-烷基酰胺酯类（A）、N-烷基酰胺类（B）两类共20种新化合物，并用UPLC-Q-TOF-MS技术获取裂解数据，探讨其质谱裂解规律。在ESI+模式下，这20种化合物均易形成[M+H]+准分子离子。A类化合物首先发生羰基α断裂，即C—O键断裂，再发生N-位α裂解，分别形成4-羟基苯乙胺离子[M+H]+（m/z 138.091 2）和4-羟基苯乙基离子（m/z 121.063 0）；B类化合物仅发生N-位α裂解。通过多巴速率氧化法评价了NAAs衍生物的体外酪氨酸激活活性，结果表明，该类化合物具有较好的激活体外酪氨酸酶活性，其中H2优于阳性对照药8-MOP。该研究可为NAAs类化合物的结构分析及开发应用提供参考依据。Abstract: Twenty kinds of N-alkylamides analogues of N-alkylamide esters (A) and N-alkylamides (B) were synthesized by condensation reaction with the N-alkylamides from the root of Anaycclus pyrethrum (L) DC as the lead compounds, HATU as condensation agent, tyramine and faseries of fatty acids as raw material and all of them were new compounds. The results showed that the synthetic route was mild, stable and reliable, and could be used as a way to obtain NAAs derivatives. In order to provide data support for the structure identification of N-alkylamides, mass fragmentation mechanism of 20 N-alkylamides was studied. All the 20 compounds were easy to obtain [M+H]+ at positive ion mode. Class A compounds lost carbonyl alpha at the first, followed by N-position alpha cleavage to form m/z 138.091 2 and m/z 121.063 0, respectively. However, class B compounds were characterized only by N-position alpha cleavage. In vitro tyrosine activation of NAAs derivatives was evaluated by dopa rate oxidation method. The results showed that these compounds had better activity of tyrosinase in vitro, and H-2 was superior to 8-MOP. And it was found that the compounds with phenolic hydroxyl had a greater effect on the activation of mushroom tyrosinase, indicating that phenolic hydroxyl might be the active group for the activation of mushroom tyrosinase. Moreover, from compound H-1 to H-20, the carbon chain increased gradually, and the activation of mushroom tyrosinase decreased gradually, which indicated that the carbon chain length of naas derivatives would affect the activation of mushroom tyrosinase, and the longer the carbon chain, the weaker the activation. The study can provide some references for the structural analysis and application of NAAs.
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Keywords:
- Anacyclus pyrethrum /
- N-alkylamide analogues /
- synthesis /
- fragmentation pathways /
- tyrosinase
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