【作者】 庞怀林；

【导师】 尹笃林；

【作者基本信息】 湖南师范大学 ， 有机化学， 2007， 博士

【摘要】 21世纪的农药在高效、安全、经济、环境友好等方面提出了更高的要求。四取代苯类除草剂为原卟啉原氧化酶(protox)抑制剂,属需光型除草剂,其独特的除草机制可保证动植物之间的良好选择性,具有十分广阔的发展前景。本文以商品化的protox抑制剂氟丙嘧草酯、丙炔氟草胺等除草剂为先导,针对它们物理性能或生物活性等方面的某些缺陷,采用活性亚结构拼接、生物电子等排体等农药分子设计方法,设计并合成了N-苯基脲嘧啶-2-异吲哚二酮、N-苯基脲嘧啶-3-芳(烷)基脲、N-苯基脲嘧啶-N-苯氧乙(丙)酰胺、N-苯基脲嘧啶-N-芳(烷)酰胺、吡咯烷酮取代苯并噁嗪、N-苯并噁嗪-2-异吲哚二酮乙酰胺、N-苯并噁嗪苯甲酰胺和丙炔氟草胺碘加成物等八个系列九类共92个具有潜在protox抑制剂活性的新型脲嘧啶和苯并噁嗪衍生物,所有化合物结构经核磁共振、质谱、红外光谱、元素分析等检测方法进行了确证。首次在苯基取代脲嘧啶结构类型中引入脲基团和苯氧丙酰胺基团,首次在苯并噁嗪衍生物中引入吡咯烷酮基团,研究结果丰富和扩展了四取代苯和protox抑制剂的结构类型。采用农药生物活性测定标准操作程序测试了所合成的新化合物的除草活性,发现一些化合物表现出较高的protox抑制活性,如2个N-苯基脲嘧啶-N-苯氧丙酰胺衍生物、2个N-苯基脲嘧啶-N-烷酰胺衍生物的除草活性和对作物安全性与先导化合物氟丙嘧草酯基本相当;4个N-苯基脲嘧啶-1-烷基脲衍生物在75 g ai/ha剂量下芽前或芽后施用对苘麻、藜、凹头苋等双子叶杂草和马唐、稗草、狗尾草等单子叶杂草均表现出80%以上除草活性。杂草中毒症状有叶片白化、卷曲、灼伤和坏死等,属protox抑制剂典型的除草特征。解析了化合物N-(3-氧-4-乙基-7-氟-2H-[1,4]苯并噁嗪-6-基)-2-硝基-4-甲磺酰基苯甲酰胺和化合物2-[4-(2,3-二碘-丙-2-烯基)-7-氟-3-氧-3,4-二氢-2H-[1,4]l苯并噁嗪-6-基]-4,5,6,7-四氢-2H-异吲哚-1,3-二酮的单晶结构,通过分析~1H NMR与X-射线晶体衍射实验计算数据,揭示了分子中环的构型和氢键情况,为进一步设计具有生物活性的化合物提供了有价值的参考信息和实验数据。围绕具有自主知识产权的新化合物B2005工业技术开发的需要,发现了以醋酸为溶剂、氯化碘为碘化剂取代丙炔氟草胺的端炔氢合成B2055的新合成方法,具有反应时间短,收率高、反应条件温和等特点;与原有采用碘代丁二酰亚胺为碘化剂的方法比较,收率基本相当,含量高于95%,较大幅度地降低了原材料成本,具有较大的应用价值。通过新化合物结构与除草活性之间的定性构效关系研究,揭示了脲嘧啶、苯并噁嗪衍生物结构与活性之间的规律,研究成果对于今后protox抑制剂类新农药的分子设计和先导优化研究具有指导意义。更多还原

【Abstract】 In the 21^th century, pesticide must have the characteristics of high effect, safety, low cost and environmentally-friend. Tetra-substituded benzene herbicides are Protoporphyriinogen oxidase （protox） inhibitors and light-dependent herbicides, which will be found a wider application because their unique herbicidal mechanism can ensure very good selectivity between human, animals and plants.To overcome limitations of some lead compounds in physical property and biological activity, some novel compounds with latent protox inhibiting activity were designed by choosing commercial protox inhibitor butafenacil, flumioxazin and other herbicides as lead compounds based on pesticide molecular design technologies, such as activity sub-structure connecting and bioisosteric replacement; 9 kinds 92 novel uracil and benzoxazine derivatives were prepared and purified, and these compounds could be divided into 8 series: N-phenyluracil-2-isoindolinedione, N-phenyluracil-3-phenyl（alkyl）ur-ea, N-phenyluracil-N-acet（propan）amide, N-phenyluracil-N-benz（alkyl）am-ide, oxopyrrolidine substituted benzoxazine, N-benzoxazine-2-isoindoline-dione acetamide, N-benzoxazinebenzamide and two iodine substituted flumioxazin. Their structures were confirmed by ¹H NMR, IR, mass spectroscopy and elemental analysis. The first introduction of phenox-ypropanamide and urea group into phenyluracil derivatives and that of 2-oxo-pyrrolidine group into benzoxazine derivatives expanded the chemical structural types of tetra-substituded benzene and protox inhibitors.The bioassays of preliminary herbicidal activity were carried out according to the standard operation procedure of pesticide bioassay, and the results showed that many compounds exhibited higher inhibiting protox activity. For example, two compound of N-phenyluracil-N-propanamide derivatives and two compound of N-phenyluracil-N-alkylamide derivatives had comparable herbicidal activity as butafenacil, four compounds of N-phenyluracil-1-alkyurea derivatives possessed more than 80% herbicidal efficiency at 75 g ai/ha in both pre- and post-emergence treatments against both dicotyledon weeds such as Abutilon theophrasti M, Chenopodiun album L, Amaranthus retroflexus L and monocotyledon weeds such as Digitaria sanguinalis L, Echinochloa crus-galli L, Setaria viridis L. The injury symptoms against weeds included leaf cupping, crinkling, bronzing and necrosis, typical of protox inhibitor herbicides.The crystal of N-（4-ethyl-7-fluoro-3-oxo-3,4-dihydro-2H-benzo[b][1 ,4]-oxazin-6-yl）-4-（methylsulfonyl）-2-nitrobenzamideand2-{4-[（E）-2,3-diiodoa-llyl]-7-fluoro-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl}-4,5,6,7-tetrah-ydro-2H-isoindole-1,3-dione was parsed. The results of ¹H NMR and X-ray crystallographic measurement showed the information of ring conformations and hydrogen bonds in the molecule, which offered a valuable information and fact evidence for the further design of bio-active compounds.A new synthesis method of B2055 was discovered, in which chloride iodine was used as iodide reagent and acetic acid as solvent, with 90.7% yield and 95% purity. The method showed more economical and industrialized value.Qualitative study on the relationship between chemical structure and herbicidal activity outlined their orderliness. The results could be used to guide the further research for the design of novel pesticide molecules and the modification of lead compounds.更多还原