甲氧基丙烯酸酯类杀菌剂是以天然产物Strobilurin A和Oudemasin A为先导而开发的新型细胞色素bcl复合物Qo抑制剂，是一类高效、广谱及环境友好的新型杀菌剂，目前它已成为世界杀菌剂市场上最主要的品种，占据了市场份额的20％以上。随着抗性的产生，研究结构新颖的新一代反抗性的甲氧基丙烯酸酯类杀菌剂成为该领域内一个具有挑战性的课题。

    为了寻求高活性的先导结构，本文以商品化品种和文献报道的高活性化合物作为先导结构，根据活性亚结构拼接、生物等排取代等方法对甲氧基丙烯酸酯类衍生物的侧链部分开展深入的结构优化研究。具体研究内容如下：

  1、 对甲氧基丙烯酸酯类杀菌剂的天然产物结构、开发历程、结构修饰、合成、作用机制和抗性等方面的研究进展进行了系统总结。

  2、  设计合成了二类共31个侧链结构新颖的甲氧基丙烯酸酯类衍生物。采用1H NMR、MS、IR和元素分析对所合成的化合物进行了系统的结构表征。

  3、 测试了所有化合物的杀菌活性，发现大部分化合物具有较好的杀菌活性。在50µgmL-1浓度下，测定了所有化合物对西瓜炭疽病、番茄灰霉病和辣椒疫霉病的杀菌活性。尤其是化合物1b，2a和2k对所​​有供试真菌的抑制活性都比商业化嘧菌酯效果好。

The β-methoxyacrylate fungicides are outstanding new class of cytochrome bc1 complex Q_o-site inhibitors, and this class of fungicides is based on a group of natural lead derivatives of (E)-methyl β-methoxyacrylate, such as strobilurin A and oudemasin A. With stronger biological activities, broader antifungal spectrum, lower toxicity toward mammalian cells, and security, the strobilurins have been one of the most important classes of agricultural fungicides and might in the near future assume the number one position in the market, represent more than 20 percent of the world fungicide market. However, with a range of strobilurin fungicides for important plant pathogens being used in a short period of repeated field, significant increases in resistance have been observed. Therefore, discovering new strobilurin analogues with high biological activities against resistant pathogens has attracted much attention from agricultural chemists in recent years and become a challenged project in pesticidal field.

In order to search for novel lead-structure with high activities, the side chain of the strobilurins derivatives were optimized from commercialized strobilurins and high bioactive compounds the literature reported, base on the active substructure combination and bioisosteric replacement, this dissertation including as follows:

     1.      The strobilurin derivatives are summarized in the paper, and the review describes in detail their structure of natural structure, history of development, structure optimization, synthesis methods, biochemical mode of action and resistance risk.

2.      Thirty-one strobilurin derivatives with novel side chains were designed and synthesized by multiple step synthetic procedures. The compounds were confirmed and characterized by IR, ¹H-NMR, elemental analysis and mass spectroscopy. The structures are shown as follows:

3.          The bioactivity of all the target compounds was tested. The bioassays showed that most of the β-methoxyacrylate analogues exhibited potential antifungal activities against Colletotrichum orbiculare, Botrytis cinerea Persand Phytophthora capsici Leonian.It is worth mentioning that compound 1b，2a and 2k exhibited better antifungal activity against all the tested fungi than azoxystrobin.