吗啉磺酰胺化合物的设计、合成及其抑制大豆萌芽活性的研究

Design and Synthesis of Morpholine Sulfonamide Compound and Its Inhibition on Soybean Seed Germination

为了发现新型脱落酸功能类似物,采用活性亚结构拼接原理设计了含吗啉磺酰胺片段的目标分子.以吗啉-4-磺酰胺和氟代硝基苯为起始原料,经芳基亲核取代反应合成了14个目标化合物,该合成方法操作简单,底物适用范围广.种子萌芽实验结果表明,浓度为50µmol/L时4a~4d、4k、4m、4n等7个化合物处理后完全抑制萌芽,25µmol/L时4a~4d、4k、4m、4n等7个化合物处理后抑制率仍高于95%.进一步降低至15μmol/L时,发现4m、4n的抑制活性高于ABA和先导化合物PM4.分子对接结果表明,引入吗啉促使小分子中磺酰基(SO2)与Ser98形成氢键,提高了结合受体的能力,所以4m和4n的打分函数高于ABA和PM4,活性也更高.该结果有利于发现新型脱落酸功能类似物.

In order to obtain novel abscisic acid analogues,morpholine-sulfonamide compound was designed under the principle of active substructure combination.14 target compounds were obtained through aromatic nucleophilic substitution(SNAr)when fluoride nitrobenzene and morpholine-4-sulfonamide were used as starting materials.The approach represents simple operation and broad substrate scope.Additionally,the soybean seed germination was inhibited overwhelmingly when treated with compounds 4a~4d,4k,4m and 4n at 50μmol/L.Furthermore,the inhibition activity of compounds 4a~4d,4k,4m and 4n was higher than 95%at 25μmol/L.Finally,the activity of 4m and 4n was much higher than that of ABA and lead compound(PM4)at 15μmol/L.Moreover,the molecular docking study revealed that 4m and 4n could bind abscisic acid receptor strongly than ABA and PM4.These results are benefit to discovering novel ABA analogues.