三氟乙酰基取代螺吲哚酮六氢吡咯里嗪衍生物的构建及抑菌活性研究

张睿; 张茵; 李文娟; 韩小强; 赵吉星

doi:10.6023/cjoc202503011

有机化学 >

2025 , Vol. 45 >Issue 9: 3378 - 3391

DOI: https://doi.org/10.6023/cjoc202503011

研究论文

三氟乙酰基取代螺吲哚酮六氢吡咯里嗪衍生物的构建及抑菌活性研究

张睿 ^a ,
张茵 ^a ,
李文娟 ^,^a^,^* ,
韩小强 ^,^b^,^* ,
赵吉星 ^c

展开

^a 石河子大学化学化工学院新疆兵团化工绿色过程重点实验室新疆石河子 832003
^b 石河子大学农学院新疆绿洲农业病虫害治理与植物资源利用重点实验室新疆石河子 832003
^c 石河子大学分析测试中心新疆石河子 832003

收稿日期: 2025-04-17

修回日期: 2025-05-02

网络出版日期: 2025-05-29

基金资助

石河子大学高层次人才启动(RCZK2021B08)

石河子大学创新发展专项(CXFZ202303)

收起

Construction and Antifungal Activity Study of Trifluoroacetyl Substituted Spiro Indolinone-Hexahydropyrrolizine Derivatives

Rui Zhang ^a ,
Yin Zhang ^a ,
Wenjuan Li ^,^a^,^* ,
Xiaoqiang Han ^,^b^,^* ,
Jixing Zhao ^c

Expand

^a Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi, Xinjiang 832003
^b Key Laboratory for Oasis Agricultural Pest Management and Plant Protection Resources Utilization, College of Agriculture, Shihezi University, Shihezi, Xinjiang 832003
^c Analysis and Testing Center, Shihezi University, Shihezi, Xinjiang 832003

^* E-mail: lwj01_tea@shzu.edu.cn;

hanshz@shzu.edu.cn

Received date: 2025-04-17

Revised date: 2025-05-02

Online published: 2025-05-29

Supported by

High Level Talents Launch Project of Shehezi University(RCZK2021B08)

Special Project of Innovation and Development of Shehezi University(CXFZ202303)

Fold

摘要

通过靛红、L-脯氨酸反应生成的亚甲胺叶立德可与三氟甲基α,β-不饱和酮发生[3＋2]环加成反应, 高效构建三氟乙酰基取代螺吲哚酮六氢吡咯里嗪. 该反应以廉价的冰乙酸为催化剂, 在甲醇中回流6 h, 以中等至优秀的产率(47%~92%)得到22个螺环化合物, 其中近半数在浓度为50 mg/L时对立枯丝核菌的抑制率超过70%. 当底物α,β-不饱和酮类衍生物1的苯基上对位有取代基时的对应产物(4ba, 4ca, 4da, 4ga)及含有Cl、Br、F取代基时的对应产物(4ia, 4ah, 4ai, 4ak)抑菌活性较好. 对抑菌率在75%以上的6个化合物测定EC₅₀值, 在8.058~19.473 mg/L之间. 相比对照药品, 三氟乙酰基的引入有效提高了螺环化合物对立枯丝核菌的抑制活性.

关键词： 吲哚酮六氢吡咯里嗪; 三氟乙酰基; 抑菌活性

本文引用格式

张睿 , 张茵 , 李文娟 , 韩小强 , 赵吉星 . 三氟乙酰基取代螺吲哚酮六氢吡咯里嗪衍生物的构建及抑菌活性研究[J]. 有机化学, 2025 , 45(9) : 3378 -3391 . DOI: 10.6023/cjoc202503011

Abstract

The azomethine ylide through the reaction of isatin with L-proline, undergoes a [3＋2] cycloaddition reaction with trifluoromethyl α,β-unsaturated ketones. This reaction could efficiently construct trifluoroacetyl substituted spiro indolinone- hexahydropyrrolizine compound. The reaction used inexpensive glacial acetic acid as a catalyst, methanol as solvent, and refluxed for 6 h. A series of spiro compounds were obtained with moderate to excellent yields (47%~92%). Nearly half of the compounds showed an inhibition rate of over 70% against Rhizoctonia solani at a concentration of 50 mg/L. If the product contains para-substituents on the phenyl group of substrate 1 (4ba, 4ca, 4da, 4ga), or if the product contains Cl, Br, F substituents (4ia, 4ah, 4ai, 4ak), the antibacterial activity is better. There are 6 compounds that the initial screening result is greater than 75%. The EC₅₀ values of these compounds are between 8.058 and 19.473 mg/L. Compared to the control drug, the introduction of trifluoroacetyl effectively enhanced the inhibitory activity of spirocyclic compounds against Rhizoctonia solani.

Key words： indolinone hexahydropyrrolizine; trifluoroacetyl; fungicidal activity

靛红含有吲哚骨架且具备良好的成环反应活性^[1], 被广泛用于氮杂环的合成反应研究中^[2], 它可与α-氨基酸经脱羧反应后生成亚甲胺叶立德, 经有机酸催化与亲偶极体进行1,3-偶极环加成, 得到螺吲哚酮吡咯烷衍生物^[3], 该结构常见于天然生物碱中, 有抗糖尿病、抗寄生虫、抗癌和抗菌活性^[4], 引起了学者们的关注^[5], 例如可用于癌症治疗的MDM2抑制剂以及多种存在于植物中有毒但具有药用价值的茶碱(图1).

显示原图|下载原图ZIP|生成PPT

图1 具有生物活性的螺吲哚酮吡咯烷衍生物

Figure 1 Spiroindolone pyrrolidine derivatives with biological activity

当α-氨基酸选用L-脯氨酸时, 可构建六氢吡咯里嗪结构. 2014年, Klochkova等^[3b]发表了共轭不饱和酮与亚

甲胺叶立德的1,3-偶极环加成反应, 以较好的区域选择性构筑螺吲哚酮六氢吡咯里嗪骨架(Scheme 1a).

显示原图|下载原图ZIP|生成PPT

图式1 亚甲胺叶立德的环加成反应

Scheme 1 Cycloaddition reactions of azomethine ylide

2022年, Mataji等^[3e]对所构建的吲哚酮取代螺吲哚酮六氢吡咯里嗪衍生物(Scheme 1b)进行抑菌活性测试, 证实其对金黄色葡萄球菌(MTCC 96)、枯草芽孢杆菌(MTCC 121)、大肠杆菌(MTCC 1652)、铜绿假单胞菌4种细菌有较好的体外抑制活性, 但该报道并未继续探究该化合物对真菌的体外抑菌效果.

新疆是我国农作物种植的重要地区, 多种植物病原菌的感染严重威胁了果蔬产量^[6], 对于有机合成领域来说, 为新型杀菌剂的研究提供先导化合物的意义重大. 我们尝试利用靛红与L-脯氨酸脱水脱羧后形成亚甲胺叶立德, 在乙酸催化作用下与三氟甲基取代α,β-不饱和酮进行成环反应研究, 构筑含氟基团取代的螺吲哚酮六氢吡咯里嗪基本骨架(Scheme 1c), 并探究其对三种常见的病原菌立枯丝核菌、金黄壳囊孢菌、尖孢镰刀菌的体外抑菌活性, 在探索过程中发现引入三氟甲基后反应的区域选择不同于前人的报道.

1 结果与讨论

以三氟甲基取代α,β-不饱和酮1a、市售的靛红2a、L-脯氨酸3a进行三组分反应研究(Scheme 2, 表1). 首先三底物等比例投料, 以冰乙酸为催化剂, 甲醇为溶剂, 回流温度下反应6 h, 化合物1a消耗完全, 以67%产率得到[3＋2]环加成产物螺吲哚酮六氢吡咯里嗪4aa(表1, Entry 1).

显示原图|下载原图ZIP|生成PPT

图式2 环加成反应策略

Scheme 2 Cycloaddition reaction strategy

表1 反应条件筛选^a

Table 1 Screening of reaction conditions

Entry	2a/equiv.	3a/equiv.	Cat. (equiv.)	Solvent	Yield^b/%
1	1	1	MeCOOH (0.5)	MeOH	67
2	1.25	1	MeCOOH (0.5)	MeOH	55
3	1	1.25	MeCOOH (0.5)	MeOH	71
4	1	1.5	MeCOOH (0.5)	MeOH	70
5	1.4	1.75	MeCOOH (0.5)	MeOH	69
6	1.6	2	MeCOOH (0.5)	MeOH	79
7	2	2.5	MeCOOH (0.5)	MeOH	77
8	1.6	2	MeCOOH (0.25)	MeOH	89
9	1.6	2	None	MeOH	30
10	1.6	2	HCl (1 mol/L, 0.25)	MeOH	48
11	1.6	2	TsOH (0.25)	MeOH	75
12	1.6	2	TfOH (0.25)	MeOH	81
13	1.6	2	EtCOOH (0.25)	MeOH	81
14^c	1.6	2	MeCOOH (0.25)	MeOH	86
15^c^,^d	1.6	2	MeCOOH (0.25)	MeOH	87
16	1.6	2	MeCOOH (0.25)	Toluene	Trace
17	1.6	2	MeCOOH (0.25)	DCE	Trace
18	1.6	2	MeCOOH (0.25)	1,4-Dioxane	Trace
19	1.6	2	MeCOOH (0.25)	MeCN	57
20	1.6	2	MeCOOH (0.25)	THF	72
21^e^,^f	1.6	2	MeCOOH (0.25)	MeOH	—

^a 1a (0.2 mmol), solvent (4.0 mL), the reaction is under air. ^b Isolated yield. ^c The reaction is under nitrogen gas. ^dDetect after 12 h of reaction. ^e Detect after 48 h of reaction. ^f Reaction at room temperature.

固定1a为1 equiv. (0.2 mmol), 冰醋酸为0.5 equiv. (0.2 mmol), 调整2a与3a的投料比, 发现当2a投料量大于3a时, 产率下降, 2a投料小于3a, 且投料物质的量比为1:1.25时, 发现随着2a用量的增加, 产率呈上升趋势, 当2a增加到2 equiv.时略有下降, 确定2a用量为1.6 equiv.(表1, Entries 2~7). 减少冰醋酸用量为0.25 equiv.时产率提升至89%(表1, Entry 8), 但不添加冰乙酸时产率仅有30% (表1, Entry 9). 尝试稀盐酸催化时产率降至48%(表1, Entry 10), 其他有机酸催化, 如对甲苯磺酸、三氟甲磺酸、丙酸催化时反应均有较好的产率(表1, Entries 11~13), 但仍略低于冰醋酸. 在氮气条件下反应或延长反应时间, 反应结果没有明显改善(表1, Entries 14~15), 证明空气、水的对反应影响不大. 接下来考察溶剂对反应的影响. 甲苯、1,2-二氯乙烷、1,4-二氧六环中仅监测到微量的目标产物, 溶剂为乙腈、四氢呋喃时产率分别为57%、72%, 但均低于甲醇为溶剂时的反应情况(表1, Entries 16~20). 降低反应温度至室温, 反应48 h后1a依然大量剩余(表1, Entry 21), 可见高温对于反应是有利的. 综上, 确定最优的反应条件为: 三氟甲基酮1a、靛红2a、L-脯氨酸3a的投料物质的量比1:1.6:2, 以甲醇为溶剂, 0.25 equiv.的冰乙酸为催化剂, 回流反应6 h, 以89%的产率得到目标产物4aa.

在最优条件下进行底物拓展研究, 一系列具有不同取代基的三氟甲基酮1均可与靛红、L-脯氨酸生成的亚甲胺叶立德发生1,3-偶极环加成反应, 得到对应的螺吲哚酮六氢吡咯里嗪衍生物(表2). 化合物1中苯环上带有给电子或吸电子基团取代的底物, 均可以中等至良好以上的产率得到对应的螺环产物(4ba~4ia), 但溴取代位置对产率影响较大(4ga~4ia), 邻位溴原子取代时空间位阻较大, 产率仅有47%; 将1中的苯环换为杂环噻吩后, 反应依然可以79%的良好产率得到目标产物4ja. 尝试不同取代基的靛红作为底物进行结构适应性测试, 常见吸电子和供电子基团均可以中等至良好的产率得到对应目标产物(4ab~4aj), 尤其7-溴靛红、5-溴靛红对应产物4ak、4al均以很好的产率84%、87%得到, 其中含碘取代的化合物4am只能在乙酸乙酯中溶解性较好. 4ia、4am的X射线单晶衍射实验验证产物结构. 经HPLC确认为消旋化产物.

表2 底物范围拓展^a

Table 2 Expansion of substrate scope

^a 1a (0.2 mmol), 2a (0.32 mmol), 3a (0.4 mmol), MeCOOH (0.5 mmol), solvent (4.0 mL), reflux, 6 h, the reaction is under air.

尝试不同的α-氨基酸对反应的适应性(图2), 甘氨酸、L-色氨酸及D-苯丙氨酸反应时均未得到目标产物.

显示原图|下载原图ZIP|生成PPT

图2 其他α-氨基酸的尝试

Figure 2 Attempt at other α-amino acids

根据文献调研^[3], 提出了可能的反应机理(Scheme 3). 靛红与L-脯氨酸相互作用产生中间体Ⅰ, 其中, 羧酸与羟基通过脱水反应产生螺环中间体Ⅱ, 进而发生脱羧产生亚甲胺叶立德Ⅲ. 不同于Klochkova等^[3b]的报道, 该反应在乙酸的作用下, 亲偶极体1a的羰基形成了分子间氢键, 由于空间位阻效应, 反应倾向于形成过渡态1 (TS 1), 实现[3＋2]环加成反应并进行分子内重排, 得到产物4aa. 因反应在回流温度中进行, 3的断键及后续分子内重排导致了产物的外消旋化.

显示原图|下载原图ZIP|生成PPT

图式3 可能的反应机理

Scheme 3 Possible reaction mechanisms

对化合物4aa~4ja、4ab~4al进行立枯丝核菌、金黄壳囊孢菌、尖孢镰刀菌的体外抑菌活性测试, 带药培养基药品浓度为50 mg/L, 多菌灵为市售对照药品, 结果如表3所示. 半数以上的三氟乙酰基螺吲哚酮六氢吡咯里嗪衍生物对立枯丝核菌的抑制效果良好, 均能达到60%以上的抑制率, 其中三氟甲基取代α,β-不饱和酮的底物拓展产物中, 苯环上对甲基(4ba)、对溴(4ga)、邻溴(4ia)取代时抑制率超过70%, 对氯取代(4ca)、对甲氧基(4da)取代时抑制率可达到80%以上, 以及噻吩代替苯环(4ja)时抑制率可达到87.8%; 吲哚的苯环上7-甲基(4ad)、7-溴(4ak)取代时抑制率超过70%, 7-三氟甲基(4ah)、5-氟(4ai)取代时抑制率可达到80%以上. 抑制效果较好的样品多为含卤素取代化合物, 说明卤素对提高抑菌活性有益.

表3 化合物4aa~4ja、4ab~4al在50 mg/L下的离体抑菌活性

Table 3 In vitro inhibitory activity of compounds 4aa~4ja、4ab~4al at 50 mg/L

Compd.	Inhibitory rate±SE/%
Compd.	Rhizoctonia solani	Cytospora chrysosperma	Fusarium oxysporum
4aa	59.7±2.2	36.1±1.4	55.1±3.4
4ba	70.4±1.6	29.9±1.4	62.9±3.2
4ca	80.2±0.6	54.8±0.4	50.6±1.7
4da	84.1±1.2	30.0±1.9	52.7±0.6
4ea	51.7±1.2	27.6±2.0	56.3±2.1
4fa	50.1±2.9	24.8±1.1	54.0±3.1
4ga	70.3±2.0	51.3±0.7	51.5±1.5
4ha	57.1±2.0	37.6±1.1	60.1±2.3
4ia	72.7±2.1	45.5±1.4	61.6±0.3
4ja	87.8±1.4	41.8±1.0	55.6±1.6
4ab	64.7±3.1	46.7±0.6	56.1±4.4
4ac	67.4±1.4	42.2±1.7	34.6±1.0
4ad	76.6±2.2	41.7±1.1	29.0±1.1
4ae	39.2±3.3	30.0±1.1	25.8±1.0
4af	64.2±1.0	12.0±2.0	46.5±1.2
4ag	38.9±2.1	13.3±0.5	58.8±4.0
4ah	82.5±1.1	54.6±1.1	54.4±1.3
4ai	84.6±0.7	33.0±1.5	51.4±3.0
4aj	65.4±2.1	53.7±0.3	51.3±2.0
4ak	73.5±0.6	38.9±0.5	60.9±0.9
4al	40.3±4.1	45.9±1.2	47.3±1.1
Carbendazim	94.1±1.0	96.4±0.8	97.3±0.8

但这些化合物对金黄壳囊孢菌的抑制效果并不理想, 4ca、4ah、4aj化合物抑制率在54%左右, 半数化合物抑制率低于40%; 对尖孢镰刀菌的抑制效果仅化合物4ba、4ha、4ia、4ak, 抑制率超过60%, 化合物4ad、4ae对尖孢镰刀菌的抑制率不足30%.

为了进一步评估目标化合物对立枯丝核菌的抑菌潜力, 根据Klochkova等^[3b]的文章, 选取了较为易得且无含氟基团取代的底物, 合成了对应的螺环化合物5~8(图3), 并进行带药培养基药品浓度为50 mg/L时4个化合物对立枯丝核菌的抑制率测定(如表4), 抑制率为49.8%~62.9%, 对照化合物4ba、4da、4ad、4ak可知, 在该浓度下含三氟乙酰基取代的化合物对立枯丝核菌的抑制效果显著提升.

显示原图|下载原图ZIP|生成PPT

图3 化合物5~8

Figure 3 Compounds 5~8

表4 化合物5~8在50 mg/L下的离体抑菌活性

Table 4 In vitro inhibitory activity of compounds 5~8 at 50 mg/L

Compd.	Inhibitory rate±SE/%
Compd.	Rhizoctonia solani
5	55.7±1.2
6	52.5±0.9
7	62.9±2.1
8	49.8±1.3
Carbendazim	94.8±0.7

将三氟乙酰基取代螺吲哚酮六氢吡咯里嗪系列化合物在50 mg/L浓度下初筛, 结果较好的化合物4ca、4da、4ad、4ja、4ah、4ai及对照化合物6、7进行了半数效应浓度EC₅₀的测定, 设置化合物的质量浓度梯度为50、25、12.5、6.25 mg/L. 利用IBM SPSS Statistics 27软件分析数据求得EC₅₀值, 测定结果如表5所示. 6个目标化合物对于立枯丝核菌的EC₅₀值在8.058~19.473 mg/L之间, 其中4ja对立枯丝核菌的抑菌效果最好, EC₅₀值为8.058 mg/L, 4ca、4da的EC₅₀值相当, 虽然化合物4ai在浓度为50 mg/L时抑制效果较好, 但半数效应浓度却低于其他化合物, 可推测含单氟原子取代化合物对立枯丝核菌抑制活性的提升是有限的. 无含氟基团化合物6、7的EC₅₀值分别为38.296和27.421 mg/L. 4da与6为底物酮的苯环上对位甲氧基取代的对应产物, 4ad与7均为底物靛红上7-甲基取代的对应产物. 4da、4ad的EC₅₀值均高于化合物6、7, 由此可知引入三氟乙酰基后, 螺环化合物对立枯丝核菌的抑制活性显著提高.

表5 化合物对立枯丝核菌的EC₅₀值

Table 5 EC₅₀ values of compounds against Rhizoctonia solani

Compd.	Regression equation	R²	EC₅₀/(μg•mL^-1)
4ca	y=2.083x-2.288	0.984	12.532
4da	y=2.751x-3.065	0.994	13.010
4ja	y=2.739x-2.483	0.964	8.058
4ad	y=2.763x-3.486	0.985	18.258
4ah	y=3.261x-3.896	0.978	15.657
4ai	y=3.757x-4.842	0.950	19.437
6	y=1.152x-1.833	0.988	38.296
7	y=1.608x-2.312	0.995	27.421
Carbendazim	y=1.207x＋0.476	0.998	0.404

2 结论

通过靛红、L-脯氨酸反应生成的亚甲胺叶立德与三氟甲基α,β-不饱和酮的[3＋2]环加成反应, 开发了一种低成本、简洁、高效合成三氟乙酰基取代螺吲哚酮六氢吡咯里嗪的策略. 该反应以廉价的冰醋酸作为催化剂, 甲醇作为混合溶剂, 回流6 h, 以中等至优秀的产率(47%~92%)得到一系列螺吲哚酮六氢吡咯里嗪衍生物, 在一定程度上拓展了亚甲胺叶立德1,3-偶极环加成的应用范围. 带药培养基浓度为50 mg/L时, 近半数化合物对立枯丝核菌的抑制率超过70%, 其中噻吩基取代的螺环化合物(4ja)抑菌率最高, 可达87.8%; 底物1为对位取代的对应产物(4ba、4ca、4da、4ga), 以及含Cl、Br、F卤素类取代基的化合物(4ia、4ah、4ai、4ak), 抑菌率高于70%. 对6个抑菌活性高于75%的化合物进行了立枯丝核菌的EC₅₀值测试, EC₅₀在8.058~19.473 mg/L之间, 4ja的抑菌效果最好. 通过与无含氟基团取代的化合物对照可知, 三氟乙酰基的引入有效提高了螺环化合物的抑菌活性, 螺吲哚酮六氢吡咯里嗪骨架在立枯丝核菌的抑制上有一定的应用潜力.

3 实验部分

3.1 仪器与试剂

Bruker Avnce III 400 HD型核磁共振仪(CDCl₃为溶剂, TMS为内标); Bruker Vertex型红外光谱仪(KBr压片); Waters Synaptxs型超高效液相色谱-四极杆飞行时间串联质谱仪; Bruker D8 Venture型双微焦斑单晶衍射仪. 底物1a~1j根据文献[7]方法制备, 2a~2m、3a直接购买使用. 所有试剂均为分析纯, 反应中所需无水溶剂直接购买使用.

供试病原菌立枯丝核菌(Rhizoctonia solani)、金黄壳囊孢菌(Cytospora chrysosperma)、尖孢镰刀菌(Fusarium oxysporium)均由石河子大学农学院及新疆绿洲农业病虫害治理与植物资源利用重点实验室提供, 立枯丝核菌从新疆石河子市棉花立枯病病株中分离得到, 金黄壳囊孢菌从新疆塔城乌苏市新疆杨腐烂病病株中分离得到, 尖孢镰刀菌从新疆石河子市辣椒根腐病病株中分离得到.

3.2 实验方法

3.2.1 化合物的合成

以2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4aa)为例. 将三氟甲基酮2a (0.2 mmol, 40 mg)、靛红(0.32 mmol, 47 mg)、L-脯氨酸(0.4 mmol, 46 mg)加入25 mL反应管中, 加入4 mL甲醇搅拌5 min, 然后加入冰乙酸(0.5 mmol, 3 μL), 回流6 h至薄层色谱(TLC)监测三氟甲基酮消失, 将反应液通过硅藻土过滤, 乙酸乙酯洗涤滤饼, 浓缩后快速柱色谱分离[V(PE):V(EA)=5:1], 得到目标产物2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4aa), 黄色固体, 35.6 mg, 产率89%. m.p. 87.1 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.78 (s, 1H), 7.49 (d, J=7.2 Hz, 1H), 7.15 (t, J=7.0 Hz, 1H), 7.10 (d, J=7.2 Hz, 1H), 7.04 (d, J=7.2 Hz, 1H), 6.97 (t, J=7.4 Hz, 2H), 6.87 (d, J=7.2 Hz, 2H), 6.51 (d, J=7.4 Hz, 1H), 4.78 (dd, J=12.0, 8.0 Hz, 1H), 4.40 (d, J=12.0 Hz, 1H), 3.93 (q, J=8.0 Hz, 1H), 2.71 (t, J=8.4 Hz, 1H), 2.56 (td, J=9.8, 6.4 Hz, 1H), 2.13 (h, J=5.0, 4.4 Hz, 3H), 1.87 (tt, J=12.8, 6.2 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.5 (q, J=36.0 Hz), 179.2, 140.8, 132.8, 129.6, 129.2, 128.1, 128.0, 127.7, 124.3, 123.2, 115.5 (q, J=291.7 Hz), 109.8, 77.6, 69.1, 60.3, 51.4, 48.1, 32.2, 28.8; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.14; IR (KBr) ν: 3198.7 (NH stretching vibration), 2966.8, 2870.8, 1756.5 (C=O), 1707.4 (C=O), 1620.3 (NH deformation vibration), 1472.0, 1258.8, 1202.7, 1149.5, 1061.2, 1014.0, 946.4, 844.7, 752.6, 741.0 cm^-1; HRMS (ESI) calcd for C₂₂H₂₀F₃N₂O₂ (M＋H)^＋ 401.1472, found 401.1471.

2'-(对甲苯基)-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ba): 白色固体, 36.8 mg, 产率89%. m.p. 122.3 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.40 (s, 1H), 7.40 (d, J=7.0 Hz, 1H), 7.07 (t, J=7.0 Hz, 1H), 7.01 (t, J=7.0 Hz, 1H), 6.71 (d, J=8.0 Hz, 2H), 6.67 (d, J=8.2 Hz, 2H), 6.43 (d, J=7.4 Hz, 1H), 4.67 (dd, J=12.0, 8.2 Hz, 1H), 4.28 (d, J=12.0 Hz, 1H), 3.84 (q, J=8.0 Hz, 1H), 2.62 (t, J=7.6 Hz, 1H), 2.51~2.44 (m, 1H), 2.04 (s, 6H), 1.79 (td, J=13.6, 12.4, 6.0 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.6 (q, J=36.0 Hz), 179.1, 140.7, 137.5, 129.8, 129.8, 129.1, 128.8, 127.6, 124.2, 123.1, 115.5 (q, J=291.7 Hz), 109.7, 77.5, 69.2, 60.1, 51.5, 48.0, 32.2, 28.8, 21.0; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.16; IR (KBr) ν: 3201.7 (NH stretching vibration), 2963.1, 2924.1, 2869.4, 1756.0 (C=O), 1707.4 (C=O), 1621.0 (NH deformation vibration), 1517.0, 1471.9, 1259.0, 1202.8, 1149.8, 1015.0, 844.8, 820.9, 747.5, 717.3 cm^-1; HRMS (ESI) calcd for C₂₃H₂₂F₃N₂O₂ (M＋H)^＋ 415.1628, found 415.1629.

2'-(4-氯苯基)-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ca): 粉色固体, 39.0 mg, 产率90%. m.p. 104.5 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.54 (s, 1H), 7.49 (d, J=7.0 Hz, 1H), 7.15 (dt, J=26.0, 6.8 Hz, 2H), 7.00 (d, J=8.8 Hz, 2H), 6.81 (d, J=8.8 Hz, 2H), 6.56 (d, J=7.6 Hz, 1H), 4.72 (dd, J=12.0, 8.2 Hz, 1H), 4.35 (d, J=12.0 Hz, 1H), 3.95 (p, J=8.2, 7.4 Hz, 1H), 2.80~2.69 (m, 1H), 2.57 (td, J=9.4, 6.0 Hz, 1H), 2.15 (dt, J=15.2, 7.8 Hz, 3H), 1.96~1.83 (m, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.3 (q, J=36.2 Hz), 178.9, 140.5, 133.9, 131.5, 129.3, 129.3, 129.1, 128.3, 124.2, 123.3,115.5 (q, J=291.7 Hz), 109.9, 77.4, 69.0, 59.6, 51.4, 48.0, 32.2, 28.9; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.09; IR (KBr) ν: 3198.7 (NH stretching vibration), 2966.6, 2870.4, 1756.7 (C=O), 1709.2 (C=O), 1621.5 (NH deformation vibration), 1494.7, 1471.8, 1261.3, 1202.8, 1150.4, 1039.1, 1014.3, 927.3, 844.1, 747.7, 716.7 cm^-1; HRMS (ESI) calcd for C₂₂H₁₉ClF₃N₂O₂ (M＋H)^＋ 435.1083, found 435.1086.

2'-(4-甲氧基苯基)-1'-(2,2,2-三氟乙酰基)- 1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4da): 黄色固体, 36.6 mg, 产率85%. m.p. 106.6 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.47 (s, 1H), 7.49 (d, J=7.2 Hz, 1H), 7.17 (t, J=7.0 Hz, 1H), 7.11 (t, J=7.0 Hz, 1H), 6.79 (d, J=8.4 Hz, 2H), 6.57~6.53 (m, 1H), 6.50 (d, J=8.8 Hz, 2H), 4.72 (dd, J=12.0, 8.2 Hz, 1H), 4.34 (d, J=12.0 Hz, 1H), 3.92 (q, J=8.2 Hz, 1H), 3.57 (s, 3H), 2.71 (t, J=7.6 Hz, 1H), 2.54 (td, J=9.4, 6.0 Hz, 1H), 2.12 (p, J=6.6, 5.8 Hz, 3H), 1.88 (tt, J=12.8, 6.0 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.6 (q, J=36.0 Hz), 179.2, 159.1, 140.7, 129.9, 129.1, 128.7, 124.7, 124.2, 123.1, 115.5 (q, J=291.7 Hz), 113.4, 109.7, 109.7, 77.6, 69.1, 59.8, 54.9, 51.7, 48.0, 32.2, 28.8; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.16; IR (KBr) ν: 3198.6 (NH stretching vibration), 2964.7, 2871.9, 1756.1 (C=O), 1707.3 (C=O), 1620.5 (NH deformation vibration), 1515.7, 1471.6, 1305.9, 1251.8, 1202.8, 1185.2, 1150.1, 1035.5, 1017.0, 947.7, 926.8, 833.7, 773.0, 749.6, 703.5 cm^-1; HRMS (ESI) calcd for C₂₃H₂₂F₃N₂O₃ (M＋H)^＋ 431.1578, found 431.1580.

2'-(3-甲氧基苯基)-1'-(2,2,2-三氟乙酰基)- 1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ea): 白色固体, 39.6 mg, 产率92%. m.p. 82.6 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.50~8.13 (m, 1H), 7.52 (d, J=7.2 Hz, 1H), 7.15 (dt, J=22.9, 7.5 Hz, 2H), 6.91 (t, J=7.9 Hz, 1H), 6.61 (d, J=8.2 Hz, 1H), 6.56 (d, J=7.5 Hz, 1H), 6.50 (d, J=7.6 Hz, 1H), 6.29 (s, 1H), 4.75 (dd, J=12.0, 8.2 Hz, 1H), 4.38 (d, J=12.0 Hz, 1H), 3.92 (q, J=8.2 Hz, 1H), 3.45 (s, 3H), 2.74 (t, J=7.6 Hz, 1H), 2.59 (td, J=9.2, 6.2 Hz, 1H), 2.14 (q, J=9.0, 7.2 Hz, 3H), 1.88 (dt, J=21.0, 10.8 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.5 (q, J=35.9 Hz), 178.8, 159.0, 140.8, 134.4, 129.8, 129.1, 129.1, 124.2, 123.1, 119.5, 115.5 (q, J=291.7 Hz), 114.3, 112.6, 109.7, 77.3, 69.2, 60.2, 54.8, 51.3, 48.1, 32.2, 28.9; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -76.98; IR (KBr) ν: 3223.6 (NH stretching vibration), 2926.5, 2869.9, 2358.8, 2339.0, 1756.6 (C=O), 1709.2 (C=O), 1620.9 (NH deformation vibration), 1603.1, 1489.8, 1471.7, 1327.4, 1259.3, 1208.0, 1150.5, 1041.3, 1021.7, 843.8, 753.0, 708.1 cm^-1; HRMS (ESI) calcd for C₂₃H₂₂F₃N₂O₃ (M＋ H)^＋ 431.1578, found 431.1580.

2'-(2-甲氧基苯基)-1'-(2,2,2-三氟乙酰基)- 1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4fa): 黄色固体, 34.4 mg, 产率80%. m.p. 102.4 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.30 (d, J=24.0 Hz, 1H), 7.55 (d, J=6.8 Hz, 1H), 7.30 (d, J=7.6 Hz, 1H), 7.06 (dq, J=23.0, 7.2 Hz, 3H), 6.65 (t, J=7.6 Hz, 1H), 6.53 (dd, J=13.0, 8.0 Hz, 2H), 5.17 (d, J=12.4 Hz, 1H), 4.76 (dd, J=12.2, 8.2 Hz, 1H), 3.94 (q, J=8.0 Hz, 1H), 3.27 (s, 3H), 2.72 (t, J=7.8 Hz, 1H), 2.61~2.54 (m, 1H), 2.13 (q, J=6.8, 6.0 Hz, 3H), 1.96~1.84 (m, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.6 (q, J=35.8 Hz), 179.5, 157.6, 140.3, 129.9, 128.8, 128.5, 127.6, 125.6, 122.3, 121.6, 120.2, 115.5 (q, J=291.7 Hz), 110.4, 109.1, 77.3, 69.1, 54.9, 52.1, 51.4, 48.0, 32.2, 28.9; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.26; IR (KBr) ν: 3262.7 (NH stretching vibration), 2965.3, 2872.6, 1756.3 (C=O), 1712.1 (C=O), 1621.7 (NH deformation vibration), 1604.2, 1495.4, 1471.3, 1392.2, 1254.2, 1208.2, 1150.4, 1056.7, 1031.1, 1041.6, 845.1, 751.8, 704.8 cm^-1; HRMS (ESI) calcd for C₂₃H₂₂- F₃N₂O₃ (M＋H)^＋ 431.1578, found 431.1580.

2'-(4-溴苯基)-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ga): 黄色固体, 38.2 mg, 产率80%. m.p. 114.4 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.54 (s, 1H), 7.48 (d, J=7.2 Hz, 1H), 7.19~7.09 (m, 4H), 6.75 (d, J=8.4 Hz, 2H), 6.56 (d, J=7.6 Hz, 1H), 4.71 (dd, J=12.0, 8.2 Hz, 1H), 4.34 (d, J=12.0 Hz, 1H), 3.94 (q, J=8.2 Hz, 1H)., 2.75 (t, J=7.8 Hz, 1H), 2.57 (td, J=9.4, 6.2 Hz, 1H), 2.19~2.09 (m, 3H), 1.89 (td, J=9.4, 4.6 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.2 (q, J=36.2 Hz), 178.9, 140.5, 132.0, 131.3, 129.4, 129.3, 129.3, 124.2, 123.3, 122.2, 115.5 (q, J=291.6 Hz), 109.9, 77.3, 69.0, 59.6, 51.4, 48.0, 32.2, 28.9; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.02; IR (KBr) ν: 3213.6 (NH stretching vibration), 2965.5, 2873.5, 1755.8 (C=O), 1709.3 (C=O), 1620.8 (NH deformation vibration), 1491.4, 1471.7, 1409.5, 1329.7, 1202.6, 1150.1, 1078.0, 1010.6, 843.0, 750.1, 715.2 cm^-1; HRMS (ESI) calcd for C₂₂H₁₉- BrF₃N₂O₂ (M＋H)^＋479.0577, found 479.0577.

2'-(3-溴苯基)-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ha): 粉色固体, 32.5 mg, 产率68%. m.p. 98.5 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.28 (s, 1H), 7.51 (d, J=7.2 Hz, 1H), 7.21 (t, J=7.0 Hz, 2H), 7.15 (t, J=7.0 Hz, 1H), 6.95 (s, 1H), 6.86 (dt, J=14.8, 7.8 Hz, 2H), 6.61 (d, J=7.4 Hz, 1H), 4.71 (dd, J=12.0, 8.2 Hz, 1H), 4.34 (d, J=12.1 Hz, 1H), 3.92 (q, J=8.4 Hz, 1H), 2.74 (t, J=7.6 Hz, 1H), 2.59 (td, J=9.4, 6.2 Hz, 1H), 2.15 (tt, J=12.2, 5.8 Hz, 3H), 1.96~1.84 (m, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.2 (q, J=36.1 Hz), 178.8, 140.5, 135.3, 131.1, 130.9, 129.7, 129.4, 129.2, 126.1, 124.2, 123.4, 122.2, 115.5 (q, J=291.6 Hz), 109.9, 77.3, 69.0, 59.5, 51.3, 48.1, 32.2, 28.9; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.11; IR (KBr) ν: 3195.7 (NH stretching vibration), 2969.2, 2872.4, 2361.0, 2340.9, 1757.4 (C=O), 1709.4 (C=O), 1621.7 (NH deformation vibration), 1568.7, 1472.2, 1430.1, 1333.5, 1260.3, 1202.9, 1151.0, 1078.3, 1016.2, 844.3, 745.5, 708.3 cm^-1; HRMS (ESI) calcd for C₂₂H₁₉BrF₃N₂O₂ (M＋H)^＋479.0577, found 479.0577.

2'-(2-溴苯基)-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ia): 白色固体, 22.5 mg, 产率47%. m.p. 115.4 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.17 (s, 1H), 7.65 (d, J=7.2 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.16 (t, J=7.2 Hz, 1H), 7.06 (dt, J=11.2, 7.6 Hz, 2H), 6.94 (t, J=7.6 Hz, 1H), 6.58 (d, J=7.6 Hz, 1H), 5.26 (d, J=12.0 Hz, 1H), 4.66 (dd, J=12.0, 8.2 Hz, 1H), 3.98 (q, J=7.8 Hz, 1H), 2.74 (t, J=8.0 Hz, 1H), 2.60 (td, J=9.2, 6.2 Hz, 1H), 2.21~2.10 (m, 3H), 1.94 (dt, J=15.6, 7.4 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.0 (q, J=36.1 Hz), 179.5, 140.1, 133.3, 132.6, 129.4, 129.3, 128.8, 128.2, 127.4, 126.7, 126.3, 122.7, 115.4 (q, J=291.6 Hz), 109.3, 77.3, 68.7, 56.4, 53.7, 47.7, 32.1, 29.0; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.23; IR (KBr) ν: 3415.8 (NH stretching vibration), 2964.1, 2869.8, 1756.5 (C=O), 1705.0 (C=O), 1621.2 (NH deformation vibration), 1472.1, 1437.7, 1259.5, 1203.3, 1149.8, 1028.1, 842.9, 746.9, 718.9 cm^-1; HRMS (ESI) calcd for C₂₂H₁₉BrF₃N₂O₂ (M＋H)^＋ 479.0577, found 479.0577.

2'-(2-噻吩基)-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ja): 棕色固体, 32.1 mg, 产率79%. m.p. 64.2 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.43 (s, 1H), 7.49 (d, J=7.2 Hz, 1H), 7.24 (t, J=7.4 Hz, 1H), 7.14 (t, J=7.0 Hz, 1H), 6.90 (d, J=4.0 Hz, 1H), 6.68~6.65 (m, 2H), 6.61 (d, J=3.2 Hz, 1H), 4.69 (dd, J=12.0, 7.6 Hz, 1H), 4.63 (d, J=11.8 Hz, 1H), 3.88 (q, J=7.8 Hz, 1H), 2.75 (t, J=7.6 Hz, 1H), 2.58 (td, J=9.4, 6.0 Hz, 1H), 2.14 (p, J=7.0, 5.6 Hz, 3H), 1.94~1.83 (m, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.1 (q, J=36.1 Hz), 179.1, 141.1, 135.8, 129.4, 126.5, 125.3, 124.7, 124.3, 123.3, 115.5 (q, J=291.6 Hz), 109.9, 77.1, 69.2, 55.3, 53.3, 48.3, 32.2, 28.8; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -76.87; IR (KBr) ν: 3207.2 (NH stretching vibration), 2962.4, 2871.8, 1756.7 (C=O), 1710.1 (C=O), 1621.4 (NH deformation vibration), 1471.5, 1278.9, 1241.2, 1204.6, 1151.0, 1043.9, 846.0, 753.0, 703.2 cm^-1; HRMS (ESI) calcd for C₂₀H₁₈F₃N₂O₂S (M＋H)^＋407.1036, found 407.1037.

1-甲基-2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7', 7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ab): 粉色固体, 21.5 mg, 产率52%. m.p. 110.7 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 7.56 (d, J=6.4 Hz, 1H), 7.21 (t, J=7.0 Hz, 1H), 7.14 (t, J=7.4 Hz, 1H), 7.04 (dt, J=23.2, 7.0 Hz, 3H), 6.83 (d, J=7.2 Hz, 2H), 6.48 (d, J=7.6 Hz, 1H), 4.82 (dd, J=12.0, 8.2 Hz, 1H), 4.36 (d, J=12.0 Hz, 1H), 3.96 (q, J=8.0 Hz, 1H), 2.71 (s, 4H), 2.59 (td, J=9.6, 6.0 Hz, 1H), 2.20 (td, J=12.6, 12.0, 5.4 Hz, 3H), 1.94 (dt, J=16.6, 7.8 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.6 (q, J=36.0 Hz), 176.4, 143.3, 132.8, 129.2, 129.1, 127.9, 127.8, 127.6, 123.6, 123.1, 115.5 (q, J=291.7 Hz), 107.7, 77.6, 69.5, 60.9, 51.2, 48.1, 32.2, 29.0, 25.3; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.35; IR (KBr) ν: 3192.6 (NH stretching vibration), 2964.2, 2865.0, 1754.8 (C=O), 1707.8 (C=O), 1613.4 (NH deformation vibration), 1492.9, 1470.1, 1373.2, 1351.1, 1204.8, 1150.1, 1122.4, 1086.3, 1021.2, 947.9, 752.8 cm^-1; HRMS (ESI) calcd for C₂₃H₂₂F₃N₂O₂ (M＋H)^＋ 415.1628, found 415.1629.

5-甲基-2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7', 7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ac): 黄色固体, 22.4 mg, 产率54%. m.p. 91.4 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 7.95 (s, 1H), 7.36 (s, 1H), 7.07 (t, J=7.2 Hz, 1H), 7.02~6.96 (m, 3H), 6.87 (d, J=7.4 Hz, 2H), 6.44 (d, J=7.8 Hz, 1H), 4.77 (dd, J=12.0, 8.2 Hz, 1H), 4.38 (d, J=12.0 Hz, 1H), 3.92 (q, J=8.0 Hz, 1H), 2.72 (t, J=7.6 Hz, 1H), 2.61~2.55 (m, 1H), 2.38 (s, 3H), 2.20~2.09 (m, 3H), 1.94~1.85 (m, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.6 (q, J=36.0 Hz), 178.7, 138.1, 132.9, 132.7, 129.7, 129.5, 128.1, 127.9, 127.7, 124.8, 115.5 (q, J=291.7 Hz), 109.3, 77.5, 69.2, 60.2, 51.4, 48.1, 32.2, 28.8, 21.2; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.16; IR (KBr) ν: 3183.2 (NH stretching vibration), 2967.7, 2923.5, 2869.2, 1756.7 (C=O), 1706.0 (C=O), 1627.5 (NH deformation vibration), 1493.9, 1455.0, 1265.4, 1204.2, 1150.1, 1061.5, 1018.2, 854.3, 812.2, 739.2 cm^-1; HRMS (ESI) calcd for C₂₃H₂₂F₃N₂O₂ (M＋H)^＋415.1628, found 415.1629.

7-甲基-2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7', 7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ad): 黄色固体, 31.1 mg, 产率72%. m.p. 86.7 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 9.03 (d, J=14.6 Hz, 1H), 7.38 (d, J=7.0 Hz, 1H), 7.09~7.01 (m, 3H), 6.93 (t, J=7.6 Hz, 2H), 6.82 (d, J=7.4 Hz, 2H), 4.75 (dd, J=12.0, 8.2 Hz, 1H), 4.38 (d, J=12.0 Hz, 1H), 3.96~3.88 (m, 1H), 2.72 (t, J=7.6 Hz, 1H), 2.52 (td, J=9.4, 6.2 Hz, 1H), 2.18~2.04 (m, 6H), 1.96~1.87 (m, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.5 (q, J=35.9 Hz), 180.0, 180.0, 139.4, 132.8, 130.6, 129.3, 128.0, 127.9, 127.6, 123.1, 121.5, 119.0, 115.5 (q, J=291.7 Hz), 77.9, 69.2, 60.4, 51.4, 48.1, 32.2, 28.9, 15.7; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.25; IR (KBr) ν: 3183.1 (NH stretching vibration), 2965.3, 2866.9, 1756.7 (C=O), 1701.7 (C=O), 1628.8 (NH deformation vibration), 1607.1, 1457.2, 1274.6, 1203.8, 1145.6, 1063.1, 1017.9, 839.0, 747.4 cm^-1; HRMS (ESI) calcd for C₂₃H₂₂F₃N₂O₂ (M＋H)^＋ 415.1628, found 415.1629.

5,7-二甲基-2'-phenyl-1'-(2,2,2-三氟乙酰基)-1',2',5', 6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ae): 黄色固体, 35.5 mg, 产率83%. m.p. 155.6 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 9.07 (d, J=14.8 Hz, 1H), 7.21 (s, 1H), 7.03 (t, J=7.2 Hz, 1H), 6.92 (t, J=7.8 Hz, 2H), 6.83 (d, J=7.2 Hz, 3H), 4.74 (dd, J=12.0, 8.2 Hz, 1H), 4.37 (d, J=12.0 Hz, 1H), 3.91 (q, J=8.2 Hz, 1H), 2.72 (t, J=7.8 Hz, 1H), 2.51 (td, J=9.4, 6.4 Hz, 1H), 2.37 (s, 3H), 2.17~2.02 (m, 6H), 1.96~1.87 (m, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.5 (q, J=35.9 Hz), 179.9, 137.0, 132.9, 132.6, 131.1, 129.3, 128.0 127.8, 127.6, 122.1, 118.7, 115.5 (q, J=291.7 Hz), 77.9, 69.3, 60.3, 51.5, 48.1, 32.2, 28.9, 21.1, 15.7; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.21; IR (KBr) ν: 3181.3 (NH stret- ching vibration), 2926.1, 2867.6, 1757.2 (C=O), 1699.7 (C=O), 1628.1 (NH deformation vibration), 1481.9, 1455.2, 1266.9, 1204.1, 1148.8, 1061.7, 1013.9, 849.3, 739.8 cm^-1; HRMS (ESI) calcd for C₂₄H₂₄F₃N₂O₂ (M＋ H)^＋429.1785, found 429.1784.

5-甲氧基-2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6', 7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4af): 黄色固体, 27.5 mg, 产率64%. m.p. 86.3 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.39~8.22 (m, 1H), 7.15 (d, J=2.6 Hz, 1H), 7.06 (t, J=7.2 Hz, 1H), 6.98 (t, J=7.6 Hz, 2H), 6.87 (d, J=7.4 Hz, 2H), 6.72 (dd, J=8.4, 2.6 Hz, 1H), 6.48 (d, J=8.4 Hz, 1H), 4.77 (dd, J=12.0, 8.2 Hz, 1H), 4.37 (d, J=12.0 Hz, 1H), 3.91 (q, J=8.2 Hz, 1H), 3.84 (s, 3H), 2.72 (t, J=7.6 Hz, 1H), 2.56 (td, J=9.2, 6.0 Hz, 1H), 2.13 (t, J=7.0 Hz, 3H), 1.94~1.82 (m, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.6 (q, J=36.0 Hz), 179.0, 156.4, 133.9, 132.8, 131.1, 128.1, 127.9, 127.6, 115.5 (q, J=291.7 Hz), 114.6, 110.3, 110.2, 77.9, 69.2, 60.4, 55.8, 51.4, 48.0, 32.1, 28.8; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.24; IR (KBr) ν: 3162.2 (NH stretching vibration), 2964.1, 2868.1, 1755.2 (C=O), 1702.0 (C=O), 1607.8 (NH deformation vibration), 1490.0, 1457.5, 1270.4, 1203.9, 1150.0, 1032.1, 1016.9, 853.7, 808.9, 737.4 cm^-1; HRMS (ESI) calcd for C₂₃H₂₂- F₃N₂O₃ (M＋H)^＋431.1578, found 431.1580.

5-硝基-2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7', 7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ag): 黄色固体, 33.1 mg, 产率74%. m.p. 118.0 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.48 (d, J=2.4 Hz, 1H), 8.31 (s, 1H), 8.18 (dd, J=8.6, 2.3 Hz, 1H), 7.14 (t, J=7.4 Hz, 1H), 7.05 (t, J=7.6 Hz, 2H), 6.87 (d, J=7.4 Hz, 2H), 6.73 (d, J=8.6 Hz, 1H), 4.71 (dd, J=12.0, 8.4 Hz, 1H), 4.45 (d, J=12.0 Hz, 1H), 3.97 (td, J=8.6, 6.0 Hz, 1H), 2.77 (t, J=7.4 Hz, 1H), 2.58 (td, J=9.2, 6.4 Hz, 1H), 2.24~2.06 (m, 3H), 2.00~1.87 (m, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 190.8 (q, J=36.3 Hz), 146.2, 144.1, 131.9, 131.3, 128.4, 127.6, 126.3, 120.3, 115.4 (q, J=291.7 Hz), 109.6, 77.3, 69.2, 60.7, 51.4, 48.0, 32.1, 28.9; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.25; IR (KBr) ν: 3103.1 (NH stretching vibration), 2922.5, 2869.7, 1752.1 (C=O), 1722.1 (C=O), 1626.9 (NH deformation vibration), 1606.7, 1526.6, 1479.0, 1452.1, 1338.1, 1261.1, 1203.2, 1150.8, 856.9, 832.5, 761.5, 733.3 cm^-1; HRMS (ESI) calcd for C₂₂H₁₉F₃N₃O₄ (M＋H)^＋446.1323, found 446.1323.

2'-苯基-1'-(2,2,2-三氟乙酰基)-7-(三氟甲基)-1',2',5', 6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ah): 黄色固体, 30.4 mg, 产率65%. m.p. 142.3 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.68 (d, J=23.0 Hz, 1H), 7.75 (d, J=7.4 Hz, 1H), 7.42 (d, J=8.0 Hz, 1H), 7.24 (t, J=8.0 Hz, 1H), 7.11 (t, J=7.4 Hz, 1H), 6.99 (t, J=7.6 Hz, 2H), 6.80 (d, J=7.4 Hz, 2H), 4.76 (dd, J=12.0, 8.2 Hz, 1H), 4.38 (d, J=12.0 Hz, 1H), 3.94 (q, J=7.4, 6.2 Hz, 1H), 2.75 (t, J=7.6 Hz, 1H), 2.60 (td, J=9.2, 6.2 Hz, 1H), 2.29~2.03 (m, 3H), 1.93 (p, J=9.6 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.4 (q, J=36.2 Hz), 178.9, 138.2, 132.1, 131.7, 128.2, 127.6, 127.3, 126.0 (q, J=4.1 Hz), 123.6 (q, J=272.9 Hz), 122.8, 115.5 (q, J=291.7 Hz), 112.1 (q, J=33.2 Hz), 76.7, 69.3, 60.7, 51.0, 48.1, 32.1, 28.9; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -59.27, -77.33; IR (KBr) ν: 3207.2 (NH stretching vibration), 2968.2, 2870.5, 1756.8 (C=O), 1719.3 (C=O), 1622.4 (NH deformation vibration), 1456.9, 1342.2, 1195.9, 1154.2, 1127.0, 1017.0, 968.9, 846.0, 749.9 cm^-1; HRMS (ESI) calcd for C₂₃H₁₉F₆N₂O₂ (M＋H)^＋ 469.13452, found 469.13489.

5-氟-2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ai): 黄色固体, 31.3 mg, 产率75%. m.p. 82.7 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.38 (d, J=24.2 Hz, 1H), 7.29 (dd, J=7.8, 2.6 Hz, 1H), 7.09 (t, J=7.2 Hz, 1H), 7.01 (t, J=7.6 Hz, 2H), 6.93~6.83 (m, 3H), 6.50 (dd, J=8.4, 4.2 Hz, 1H), 4.74 (dd, J=12.0, 8.2 Hz, 1H), 4.36 (d, J=12.0 Hz, 1H), 3.97~3.86 (m, 1H), 2.73 (t, J=7.6 Hz, 1H), 2.55 (td, J=9.4, 6.2 Hz, 1H), 2.12 (dq, J=15.8, 8.0, 6.8 Hz, 3H), 1.97~1.84 (m, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.3 (q, J=36.1 Hz), 179.2, 160.8, 158.4, 136.4, 132.5, 131.8 (d, J=7.4 Hz), 128.2, 128.1, 127.6, 115.6 (d, J=23.8 Hz), 115.5 (q, J=291.7 Hz), 112.1 (d, J=24.6 Hz), 110.3 (d, J=7.8 Hz), 77.8, 69.2, 60.5, 51.4, 48.0, 32.1, 28.8; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.21, 117.29; IR (KBr) ν: 3200.4 (NH stretching vibration), 2962.2, 2926.5, 2870.8, 1757.0 (C=O), 1708.7 (C=O), 1630.1 (NH deformation vibration), 1485.5, 1458.7, 1273.3, 1203.8, 1150.0, 1061.7, 1016.7, 856.6, 814.2, 739.7 cm^-1; HRMS (ESI) calcd for C₂₂H₁₉F₄N₂O₂ (M＋ H)^＋419.1378, found 419.1379.

5-氯-2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4aj): 黄色固体, 29.9 mg, 产率69%. m.p. 90.7 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.27~7.92 (m, 1H), 7.54 (d, J=2.2 Hz, 1H), 7.17 (dd, J=8.2, 2.2 Hz, 1H), 7.10 (t, J=7.2 Hz, 1H), 7.02 (t, J=7.4 Hz, 2H), 6.87 (d, J=7.4 Hz, 2H), 6.51 (d, J=8.2 Hz, 1H), 4.72 (dd, J=12.0, 8.2 Hz, 1H), 4.36 (d, J=12.0 Hz, 1H), 3.99~3.81 (m, 1H), 2.73 (t, J=7.8 Hz, 1H), 2.55 (q, J=9.0 Hz, 1H), 2.21~2.03 (m, 3H), 1.91 (dt, J=15.4, 8.8 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.2 (q, J=36.2 Hz), 178.7, 139.0, 132.4, 131.8, 129.2, 128.7, 128.2, 128.1, 127.6, 124.7, 115.5 (q, J=291.7 Hz), 110.6, 77.6, 69.2, 60.5, 51.4, 48.0, 32.1, 28.9; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.05; IR (KBr) ν: 3201.3(NH stretching vibration), 2968.2, 2868.7, 1756.5 (C=O), 1709.8 (C=O), 1619.8 (NH deformation vibration), 1475.6, 1267.8, 1203.7, 1151.4, 1062.1, 1017.2, 849.0, 815.6 cm^-1; HRMS (ESI) calcd for C₂₂H₁₉ClF₃N₂O₂ (M＋H)^＋ 435.1083, found 435.1086.

7-溴-2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4ak): 白色固体, 40.2 mg, 产率84%. m.p. 158.5 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.29 (s, 1H), 7.50 (d, J=7.2 Hz, 1H), 7.34 (s, 1H), 7.12~6.97 (m, 4H), 6.87 (d, J=7.6 Hz, 2H), 4.75 (dd, J=12.0, 8.2 Hz, 1H), 4.38 (d, J=12.0 Hz, 1H), 3.96~3.87 (m, 1H), 2.73 (t, J=7.6 Hz, 1H), 2.56 (td, J=9.2, 6.2 Hz, 1H), 2.21~2.06 (m, 3H), 1.92 (qd, J=11.4, 10.8, 6.0 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.3 (q, J=36.1 Hz), 178.4, 140.0, 132.3, 131.9, 131.5, 128.2, 127.6, 124.3, 123.0, 115.5 (q, J=291.7 Hz), 102.8, 78.7, 69.3, 60.6, 51.3, 48.0, 32.2, 29.0; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.12; IR (KBr) ν: 3191.1 (NH stretching vibration), 2968.3, 2868.2, 1756.9 (C=O), 1712.2 (C=O), 1618.4 (NH deformation vibration), 1472.6, 1452.0, 1271.3, 1204.5, 1150.9, 1016.2, 844.5, 766.1, 740.0 cm^-1; HRMS (ESI) calcd for C₂₂H₁₉BrF₃N₂O₂ (M＋H)^＋ 479.0577, found 479.0577.

5-溴-2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4al): 黄色固体, 41.6 mg, 产率87%. m.p. 103.0 ℃; ¹H NMR (400 MHz, Chloroform-d) δ: 8.30 (s, 1H), 7.68 (d, J=1.8 Hz, 1H), 7.32 (dd, J=8.2, 2.0 Hz, 1H), 7.09 (t, J=7.2 Hz, 1H), 7.01 (t, J=7.4 Hz, 2H), 6.87 (d, J=7.6 Hz, 2H), 6.46 (d, J=8.2 Hz, 1H), 4.71 (dd, J=12.0, 8.2 Hz, 1H), 4.36 (d, J=12.0 Hz, 1H), 3.97~3.82 (m, 1H), 2.73 (t, J=7.6 Hz, 1H), 2.54 (td, J=9.2, 6.2 Hz, 1H), 2.21~2.04 (m, 3H), 1.90 (dt, J=14.8, 8.2 Hz, 1H); ¹³C NMR (101 MHz, Chloroform-d) δ: 191.2 (q, J=36.2 Hz), 178.7, 139.5, 132.4, 132.1, 128.2, 128.2, 127.6, 127.5, 115.9, 115.5 (q, J=291.7 Hz), 111.1, 77.6, 69.2, 60.5, 51.4, 48.0, 32.1, 28.8; ¹⁹F NMR (376 MHz, Chloroform-d) δ: -77.09; IR (KBr) ν: 3179.1 (NH stretching vibration), 2967.4, 2868.9, 1756.3 (C=O), 1709.6 (C=O), 1618.0 (NH deformation vibration), 1473.3, 1266.4, 1200.1, 1150.8, 1016.5, 847.9, 813.5, 739.8 cm^-1; HRMS (ESI) calcd for C₂₂H₁₉BrF₃N₂O₂ (M＋H)^＋ 479.0577, found 479.0577.

5-碘-2'-苯基-1'-(2,2,2-三氟乙酰基)-1',2',5',6',7',7a'-六氢螺[吲哚啉-3,3'-吡咯里嗪]-2-酮(4am): 白色固体, 39.5 mg, 产率75%. m.p. 95.1~95.6 ℃; IR (KBr) ν: 3213.5 (NH stretching vibration), 2963.2, 2869.2, 1757.2 (C=O), 1710.1 (C=O), 1614.8 (NH deformation vibration), 1471.6, 1429.5, 1268.6, 1201.4, 1150.3, 1081.8, 1016.0, 947.9, 890.1, 811.4, 736.4 cm^-1; HRMS (ESI) calcd for C₂₂H₁₉IF₃N₂O₂ (M＋H)^＋ 527.0438, found 527.0434.

3.2.2 抑菌活性测定

采用菌丝生长速率法^[8]测定化合物4aa~4ja、4ab~4al对3种供试植物病原菌的抑菌活性. 预先将5 mg目标化合物溶解于1 mL二甲基亚砜(DMSO)中, 配制成5 g/L药液待用. 以质量浓度50 mg/L带药培养基为例: 将0.75 mL的5 g/L待测药液加入到低于55 ℃的75 mL高温高压灭菌后PDA培养基中, 混合均匀, 配制成50 mg/L带药培养基, 平均倒入3个无菌培养皿中, 待培养基凝固后, 每个培养基平面中央放入1个直径5 mm(或8 mm)的供试菌饼, 每个样品处理3个重复. 以多菌灵为阳性对照, 以DMSO为阴性对照(0.75 mL DMSO加入到75 mL液体培养基中, 摇匀后平均倒入3个培养皿中). 28 ℃培养数天, 用十字交叉法测量菌落扩展直径, 按下式计算抑制率.

$ I=\frac{D_{0}-D_{\mathrm{t}}}{D_{0}} \times 100 \%$

式中: I为菌丝生长抑制率, %; D₀为阴性对照组菌落增长直径, cm; D_t为处理组菌落增长直径, mm.

辅助材料(Supporting Information) 化合物4aa~4ja、4ab~4al的¹H NMR、¹³C NMR和¹⁹F NMR谱图, 化合物5~8的¹H NMR谱图, 化合物4aa的HPLC谱图, 化合物4ia、4am的晶体结构数据, 化合物4aa~4ja、4ab~4al、5~8的抑菌活性测试图. 这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

(Cheng, F.)

参考文献

原文顺序 | 文献年度倒序 | 文中引用次数倒序

[1]

(a) Yan,

; Shi,

K.-X

; Zhao,

C.-T

; Ding,

L.-Y.

; Jiang,

S.-S.

; Yang,

L.-M.

; Zhong,

. -F Chem. Commun. 2017, 54, 1567.

(b) Wang,

H.-F.

; Xu,

Z.-H

; Deng,

G.-J

; Huang,

H.-W.

Adv. Synth. Catal. 2020, 362, 1663.

P. S.

; Patel,

K. I.

; Dhameliya,

T. M.

; Saha,

; Vaja,

M. D.

; Krishna,

V. S.

; Sriram,

; Chakraborti,

A. K.

Bioorg. Chem. 2020, 99, 103774.

(d) Li,

T.-T.

; Zhu,

X.-J.

; Jiang,

; Wang,

Y.-N.

; Zheng,

; Peng,

; Gao,

; Shi,

L.-L.

; Hao,

X.-Q.

; Song,

M.-P.

Appl. Organomet. Chem. 2021, 36, e6516

[2]

(a) Hughes,

C. C.

; Fenical,

. J. Am. Chem. Soc. 2010, 132, 2528.

(b) Wu,

H.-X.

; Xue,

; Xiao,

; Qin,

. J. Am. Chem. Soc. 2010, 132, 14052.

C.-L.

; Zhang,

X.-G.

; Tang,

R.-Y.

; Zhong,

; Li,

J.-H.

J. Org. Chem. 2010, 75, 7037.

(d) Mitsunuma,

; Shibasaki,

; Kanai,

; Matsunaga,

. Angew. Chem., Int. Ed. 2012, 51, 5217.

[3]

(a) Sudhakara,

; Kumar,

H. C. K.

; Jayadevappa,

; Mahadevan,

K. M.

Org. Chem.: Indian J. 2012, 8, 94.

(b) Klochkova,

I. N.

; Shchekina,

M. P.

; Anis’kov,

A. A.

Chem. Heterocycl. Comd. 2014, 50, 479.

K. N.

; Pandurang,

T. P.

; Pant,

; Kumar,

. Tetrahedron Lett. 2016, 57, 2286.

(d) Kolle,

; Barak,

D. S.

; Ghosh,

; Jaiswal,

; Kant,

; Batra,

. ACS Omega 2019, 4, 5617.

(e) Mataji,

; Youseftabar-Miri,

; Javan,

M. J.

; Rajabbeigi,

; Hallajian,

. J. Mol. Struct. 2022, 1270, 133891.

(f) Saleh,

F. M.

; Hassaneen,

H. M.

; Abdelhamid,

I. A.

; Teleb,

M. A. M.

Tetrahedron Lett. 2024, 137, 154957.

[4]

(a) Ding,

; Lu,

Y.-P.

; Nikolovska-Coleska,

; Wang,

G.-P.

; Qiu,

; Shangary,

; Gao,

; Qin,

D.-G.

; Stuckey,

; Krajewski,

; Roller,

P. P.

; Wang,

S.-M.

J. Med. Chem. 2006, 49, 3432.

PMID

(b) Glliford,

C. V.

; Scheid,

K. A.

Angew. Chem., Int. Ed 2007, 46, 8748.

M. M. M.

Tetrahedron 2014, 70, 9735.

(d) Ramesh,

; Rao,

K.-S.

, Trivedi,

; Kumar,

B. S.

; Prakasham,

R. S.

; Sridhar,

. RSC Adv. 2016, 6, 26546.

(e) Saraswat,

; Jeyabalan,

; Hassan,

M. Z.

; Rahman,

M. U.

; Nyola,

N. K.

Synth. Commun. 2016, 46, 1643.

(f) Ziarani, G,

; Mondi, R.; Lashgari, N. Telrahedron 2018, 74, 1323.

(g) Yu,

Q.-Z.

; Guo,

; Jian,

; Chen,

Y.-Y.

; Xu,

. Chem. Commun. 2018, 54, 1125.

(h) Al-Rashood,

S. T.

; Hamed,

A. R.

; Hassan,

G. S.

; Alkahtani,

H. M.

; Almehizia,

A. A.

; Alharbi,

; Al-Sanea,

M. M.

; Eldehna,

W. M.

J. Enzyme Inhib. Med. Chem. 2020, 35, 831.

(i) Zhou,

L.-M.

; Qu,

R.-Y.

; Yang,

G.-F.

Expert Opin. Drug Dis. 2020, 15, 603.

[5]	(a) Boddy, A. J.; Bull, J. A. Org. Chem. Front. 2021, 8, 1026. (b) Ganesh, M.; Suraj, S. Org. Biomol. Chem. 2022, 20, 5651. DOI PMID (c) Borah, B.; Veeranagaiah, N. S.; Sharma, S.; Patat, M.; Prasad, M. S.; Pallepogub, R.; Chowhan, L. R. RSC Adv. 2023, 13, 7063.

[6]

(a) Xu,

Q.-Q.

; Chen,

W.-L

; Mao,

B.-Z.

J. Nucl. Agric. Sci. 2020, 34, 2219 (in Chinese).

(徐琴琴, 陈卫良, 毛碧增, 核农学报, 2020, 34, 2219.)

DOI

(b) Yang,

C.-J

; Wang,

Y.-H.

For. Sci. Technol. 2010, 35, 27 (in Chinese).

(杨春杰, 王云华, 林业科技, 2010, 35, 27.)

Y.-X.

M.S. Thesis, Xinjiang Agricultural University, Urumqi, 2017 (in Chinese).

(尹永香, 硕士论文, 新疆农业大学,乌鲁木齐, 2017.)

(d) Zhang,

; Liu,

; Song,

J.-Y.

; Chen,

. J. Agric. Sci. Technol. 2024, 175 (in Chinese).

(张欣, 刘畅, 宋居易, 陈慧, 现代农业科技, 2024, 175.)

[7]	(a) Sanz-Marco, A.; Blay, G.; Muñozb, M. C.; Pedro, J. R. Chem. Commun. 2015, 51, 8958. (b) Zhu, T.-Z.; Shao, P.-L.; Zhang, X. Org. Chem. Front. 2021, 8, 3705.

[8]

(a) NY/T1156.2-2006, Pesticides Guidelines for Laboratory Bioactivity Tests, Part 2: Petri Plate Test for Determining Fungicide Inhibition of Mycelial Growth, Ministry of Agriculture of the Peopleʼs Republic of China, Beijing, 2006 (in Chinese).

NY/T1156.2-2006, 农药室内生物测定试验准则杀菌剂第2部分: 抑制病原真菌菌丝生长试验平皿法, 中华人民共和国农业部, 北京, 2006.)

(b) Ma,

M.-F.

; Bai,

; Zhou,

Z.-J.

; Liu,

; Zhong,

C.-M.

; Feng,

J.-L.

J. Pestic. Sci. 2023, 25, 586 (in Chinese).

(麻妙锋, 白雪, 周遵军, 刘艺, 仲崇民, 冯吉利, 农药学学报, 2023, 25, 586.)

Options

文章导航

模态框（Modal）标题

摘要

本文引用格式

Abstract

图1 具有生物活性的螺吲哚酮吡咯烷衍生物

图式1 亚甲胺叶立德的环加成反应

1 结果与讨论

图式2 环加成反应策略

表1 反应条件筛选a

表2 底物范围拓展a

图2 其他α-氨基酸的尝试

图式3 可能的反应机理

表3 化合物4aa~4ja、4ab~4al在50 mg/L下的离体抑菌活性

图3 化合物5~8

表4 化合物5~8在50 mg/L下的离体抑菌活性

表5 化合物对立枯丝核菌的EC50值

2 结论

3 实验部分

3.1 仪器与试剂

3.2 实验方法

3.2.1 化合物的合成

3.2.2 抑菌活性测定

参考文献

表1 反应条件筛选^a

表2 底物范围拓展^a

表5 化合物对立枯丝核菌的EC₅₀值