新型含氟酰胺化羟甲香豆素衍生物的合成及生物活性
收稿日期: 2017-08-17
修回日期: 2017-10-10
网络出版日期: 2017-10-20
基金资助
国家自然科学基金（No.31471808）资助项目.
Synthesis and Biological Activity of Novel Fluorinated Amide Hydroxy Methyl Coumarin Derivatives
Received date: 2017-08-17
Revised date: 2017-10-10
Online published: 2017-10-20
Supported by
Project supported by the National Natural Science Foundation of China (No. 31471808).
以羟甲香豆素为先导，利用活性亚结构拼接原理，通过引入三氟甲基及酰胺基，设计、合成了系列新型含氟酰胺化羟甲香豆素衍生物，其结构用1H NMR、13C NMR、HRMS表征，N-正丁酰基-N-间氟苄基-6-氨基-7-甲氧基-4-三氟甲基香豆素（f1）及N-对甲苯甲酰基-N-间氟苄基-6-氨基-7-甲氧基-4-三氟甲基香豆素（f9）的结构经X射线单晶衍射进一步确证.除草活性初筛表明，化合物f1、N-苯乙酰基-N-间氟苄基-6-氨基-7-甲氧基-4-三氟甲基香豆素（f13）、N-甲基丙烯酰基-N-间氟苄基-6-氨基-7-甲氧基-4-三氟甲基香豆素（f5）、N-环丙甲酰基-N-间氟苄基-6-氨基-7-甲氧基-4-三氟甲基香豆素（f7）及N-（6-氯烟酰基）-N-间氟苄基-6-氨基-7-甲氧基-4-三氟甲基香豆素（f20）对马唐幼茎的生长具有强烈抑制作用，f9、f7及N-（萘-2-甲酰基）-N-间氟苄基-6-氨基-7-甲氧基-4-三氟甲基香豆素（f17）对灰藜幼茎生长具有良好抑制作用，其抑制率高于对照药剂乙草胺.作物安全评价结果表明，化合物f1、f9及f13对双子叶作物白菜及油菜比较安全，对单子叶作物小麦及高粱比较敏感.抑菌活性评价表明，N-间溴苯甲酰基-N-间氟苄基-6-氨基-7-甲氧基-4-三氟甲基香豆（f12）、f7及f9对番茄灰霉病菌具有较好抑制作用，N-氢化肉桂酰基-N-间氟苄基-6-氨基-7-甲氧基-4-三氟甲基香豆素（f14）对苹果腐烂病菌具有较好抑制作用.
乔丽丽 , 魏艳 , 郝双红 . 新型含氟酰胺化羟甲香豆素衍生物的合成及生物活性[J]. 有机化学, 2018 , 38(2) : 509 -518 . DOI: 10.6023/cjoc201708004
Based on the structure of lead compound of 7-hydroxy-4-methyl-coumarin, a series of novel fluorinated amide coumarin derivatives were designed and synthesized through the principle of bioactive substructure combination. Their structures were characterized by 1H NMR, 13C NMR and HRMS. N-(n-Butyryl)-N-(m-fluorobenzyl)-6-amino-7-methoxy-4-trifluo-romethyl-coumarin (f1) and N-(p-methylbenzoyl)-N-(m-fluorobenzyl)-6-amino-7-methoxy-4-trifluoromethyl-coumarin (f9) were further confirmed by X-ray single crystal diffraction. The results of herbicidal activity indicated that compounds f1, N-phenylacetyl-N-(m-fluorobenzyl)-6-amino-7-methyloxy-4-trifluoromethyl-coumarin (f13), N-methylacryloyl-N-(m-fluoro-benzyl)-6-amino-7-methoxy-4-trifluoromethyl-coumarin (f5), N-(cyclopropylcarbonyl)-N-(m-fluorobenzyl)-6-amino-7-meth-oxy-4-trifluoromethyl-coumarin (f7), N-(6-chloronicotinoyl)-N-(m-fluorobenzyl)-6-amino-7-methoxy-4-trifluoromethyl-cou-marin (f20), exhibited marked inhibition against the stem growth of Digitaria sanguinalis. And f9, f7, N-(naphthalene-2-carbonyl)-N-(m-fluorobenzyl)-6-amino-7-methoxy-4-trifluoromethyl-coumarin (f17) showed excellent inhibition on the stem of Chenopodium glaucum. The herbicidal activities of the compounds mentioned above were more active than the commercial herbicide acetochlor. The results of crop safety evaluation showed that compounds f1、f9 and f13 were safe to Brassica pekinensis and Brassica napus but sensitive to Triticum aestivum and Sorghum bicolor. Furthermore, N-(m-bromobenzoyl)-N-(m-fluorobenzyl)-6-amino-7-methoxy-4-trifluoromethyl-coumarin (f12), f7 and f9 were medium active against the mycelium of phytopathogenic fungi Botrytis cinerea. And N-(hydrocinnamoyl)-N-(m-fluorobenzyl)-6-amino-7-methoxy-4-trifluoromethyl-coumarin (f14) was medium active to Valsa mali.
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