作为杀菌和杀虫先导的1,2,4-噁二嗪衍生物的设计与合成研究

doi:10.6023/cjoc202101029

摘要/Abstract

噁二嗪片段常用于小分子的修饰和构象限制, 同时噁二嗪也是一种理想的酰胺电子等排体. 基于商品化琥珀酸脱氢酶抑制剂杀菌剂的结构框架, 通过生物电子等排手段, 以噁二嗪替换酰胺结构, 设计并合成了24个1,2,4-噁二嗪类化合物. 生物活性测试结果表明, 在400 mg/L浓度下, 大部分化合物对黄瓜霜霉病表现出较好的活性. 此外, 在600 mg/L的浓度下, 这些化合物对粘虫的致死率达到100%, 说明噁二嗪的结构值得作为先导继续研究, 进而发现活性优异的新化合物.

关键词: 噁二嗪, 合成, 生物电子等排, 生物活性

Oxadiazine is an active fragment and usually is used for modification and conformation restriction of small molecules, meanwhile, it can be considered as an ideal and completely competent surrogate for the amide group. Based on the general framework of marketed succinate dehydrogenase inhibitors, twenty-four 1,2,4-oxadiazine compounds were designed and synthesized. The bioactivity test results showed that most of compounds exhibited good activities against Pseudoperonospora cubensis at 400 mg/L. In addition, the oxadiazine compounds have a 100% mortality against armyworms at 600 mg/L, which illustrates that oxadiazine structure is worth to be a lead compound and further modification to discover novel active with practical potentials.

Key words: oxadiazine, synthesis, bioisosterism, biological activities

引用此文

章乐天, 苏嘉媛, 徐晓勇. 作为杀菌和杀虫先导的1,2,4-噁二嗪衍生物的设计与合成研究[J]. 有机化学, 2021, 41(9): 3539-3549.

Letian Zhang, Jiayuan Su, Xiaoyong Xu. Design and Synthesis of 1,2,4-Oxadiazine Derivatives as Promising Fungicide and Insecticide Lead Compound[J]. Chinese Journal of Organic Chemistry, 2021, 41(9): 3539-3549.

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Compd.	R¹	R²	Inhibitory rate/%
Compd.	R¹	R²	P.C.^a	B.G.^a	P.S.^a	C.O ^a	P.O.^b	B.C.^b
A1	H	H	85	0	0	0	0	0
A5	H	4-CF₃	78	0	0	0	0	0
A6	H	4-OCF₃	90	0	0	30	50	0
A7	H	3-CH₃	85	0	0	0	0	0
A11	H	3-NO₂- 4-CH₃	98	0	0	0	50	0
CK	—	—	0	0	0	0	0	0
Mancozeb	—	—	100	—	—	—	—	—
Azoxystrobin	—	—	—	100	100	100	100	—
Pyrisoxazole	—	—	—	—	—	—	—	100

Compd.	R¹	R²	Inhibitory rate/%
Compd.	R¹	R²	P.C.^a	B.G.^a	P.S.^a	C.O ^a	P.O.^b	B.C.^b
A1	H	H	85	0	0	0	0	0
A5	H	4-CF₃	78	0	0	0	0	0
A6	H	4-OCF₃	90	0	0	30	50	0
A7	H	3-CH₃	85	0	0	0	0	0
A11	H	3-NO₂- 4-CH₃	98	0	0	0	50	0
CK	—	—	0	0	0	0	0	0
Mancozeb	—	—	100	—	—	—	—	—
Azoxystrobin	—	—	—	100	100	100	100	—
Pyrisoxazole	—	—	—	—	—	—	—	100

Compd.	R¹	R²	Inhibitory rate/%
Compd.	R¹	R²	100 mg/L	25 mg/L
A1	H	H	10	10
A2	H	2-F	30	0
A3	H	3-Br	0	0
A4	H	4-NO₂	10	0
A5	H	4-CF₃	0	0
A6	H	4-OCF₃	10	0
A7	H	3-CH₃	10	10
A8	H	4-CH₃	10	0
A9	H	4-OCH₃	20	0
A10	H	4-OPh	10	0
A11	H	3-NO₂-4-CH₃	20	0
A12	4-Cl	H	0	0
A13	4-Cl	2-F	0	0
A14	4-Cl	4-F	0	0
A15	4-Cl	3-Br	0	0
A16	4-Cl	3-CH₃	10	0
A17	4-Cl	4-CH₃	0	0
A18	4-Cl	3-NO₂-4-CH₃	0	0
A19	4-CH₃	H	50	0
A20	4-CH₃	2-F	70	0
A21	4-CH₃	4-F	0	0
A22	4-CH₃	3-Br	20	0
A23	4-CH₃	3-CH₃	0	0
A24	4-CH₃	4-CH₃	50	0
CK	—	—	0	0
Cyazofamid	—	—	100	100
Fluopyram	—	—	0	0

Compd.	R¹	R²	Inhibitory rate/%
Compd.	R¹	R²	100 mg/L	25 mg/L
A1	H	H	10	10
A2	H	2-F	30	0
A3	H	3-Br	0	0
A4	H	4-NO₂	10	0
A5	H	4-CF₃	0	0
A6	H	4-OCF₃	10	0
A7	H	3-CH₃	10	10
A8	H	4-CH₃	10	0
A9	H	4-OCH₃	20	0
A10	H	4-OPh	10	0
A11	H	3-NO₂-4-CH₃	20	0
A12	4-Cl	H	0	0
A13	4-Cl	2-F	0	0
A14	4-Cl	4-F	0	0
A15	4-Cl	3-Br	0	0
A16	4-Cl	3-CH₃	10	0
A17	4-Cl	4-CH₃	0	0
A18	4-Cl	3-NO₂-4-CH₃	0	0
A19	4-CH₃	H	50	0
A20	4-CH₃	2-F	70	0
A21	4-CH₃	4-F	0	0
A22	4-CH₃	3-Br	20	0
A23	4-CH₃	3-CH₃	0	0
A24	4-CH₃	4-CH₃	50	0
CK	—	—	0	0
Cyazofamid	—	—	100	100
Fluopyram	—	—	0	0