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取代黄酮磷酸酯的合成及抗细菌活性研究

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有机化学

Chinese Journal of Organic Chemistry

DOI: 10.6023/cjoc201701030

NOTE

取代黄酮磷酸酯的合成及抗细菌活性研究

黄阮祥辉张菊平李琴王一会

陈丽娟张橙李普薛伟*

(贵州大学精细化工研究开发中心绿色农药与农业生物工程国家重点实验室培育基地教育部绿色农药与农业生物

工程重点实验室贵阳 550025)

摘要将取代黄酮醇引入亚磷酸二乙酯, 设计合成了14个含取代黄酮基磷酸酯类新化合物, 通过1H NMR, 13C NMR,

P NMR, MS, IR和HRMS对它们的结构进行了表征. 采用浊度法测试了目标化合物的离体抑菌活性, 表明部分目标化

合物在100 µg/mL浓度下对水稻白叶枯病菌表现出良好的抑制率, 明显优于对照药剂噻菌铜和叶枯唑(≥57.4%). 其中O,O'-二乙基-O''-(2',7-二甲氧基黄酮-3-基)磷酸酯(2b)、O,O'-二乙基-O''-(2'-甲氧基-7-乙氧基黄酮-3-基)磷酸酯(2f)和O,O'-二乙基-O''-(3',4'-二甲氧基-7-乙氧基黄酮-3-基)磷酸酯(2m)在100 µg/mL浓度下对水稻白叶枯病菌的抑制率分别达到92.8%, 87.7%和88.3%. O,O'-二乙基-O''-(4'-氟-7-乙氧基黄酮-3-基)磷酸酯(2h)和O,O'-二乙基-O''-(4'-甲基-7-乙氧基黄酮- 3-基)磷酸酯(2k)在100 µg/mL浓度下对柑橘溃疡病菌也有较好的抑制活性, 其抑制率分别为85.1%和71.7%. 关键词亚磷酸酯; 黄酮醇; 黄酮磷酸酯衍生物; 抗细菌活性

Synthesis and Antibacterial Activity of Novel Phosphonate

Derivatives Containing Flavonoids

Huang, Minguo Ruan, Xianghui Zhang, Juping Li, Qin Wang, Yihui

Chen, Lijuan Zhang, Cheng Li, Pu Xue, Wei*

(State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine Chemicals, Guizhou

University, Guiyang 550025)

Abstract By introducing flavonoids group into H-phosphonate, fourteen novel phosphonate derivatives containing flavonoid unit were designed and synthesized. Their structures were characterized by 1H NMR,13C NMR, 31P NMR, MS, IR and HRMS, and their antibacterial activities were evaluated via turbidimeter test in vitro. The bioassays results reveal that part of the target compounds exhibit better activities against Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. Citri(Xac) than positive controls thiodiazole copper and bismerthiazol (≥57.4%). Among them, the inhibitory rates of (2-(2-methoxyphenyl)-7-methoxy-4-oxo-4H-chromen-3-yl)diethyl phosphonate (2b), (2-(2-methoxyphenyl)-7-ethoxy-4-oxo-4H-chromen-3-yl)diethyl phosphonate (2f) and (2-(3,4-dimethoxyphenyl)-7-ethoxy-4-oxo-4H-chromen-3-yl)diethyl phospho-nate (2m) reached 92.8%, 87.7% and 88.3% against Xoo at a concentration of 100 µg/mL, respectively. In addition, the inhibi-tory rates of (2-(4-fluorophenyl)-7-ethoxy-4-oxo-4H-chromen-3-yl)diethyl phosphonate (2h) and (2-(p-tolyl)-7-ethoxy-4-oxo-4H-chromen-3-yl)diethyl phosphonate (2k) reached 85.1% and 71.7% against Xac at a concentration of 100 µg/mL, respec-tively.

Keywords H-phosphonate; flavonol; phosphonate derivatives containing flavonoid; antibacterial activity

H-亚磷酸酯含有强极性的磷酰基(P＝O), 是一个重要的活性基团. 其特殊的结构使其具有化学活性高和反应位点多等优点, 化合物的反应多样性主要由磷原子和

烷氧基的α-碳原子两个反应中心所决定, 涉及P—H和P＝O官能键. 由于H-亚磷酸酯兼具廉价易得、易保存、结构稳定等优点, H-亚磷酸酯及其衍生物作为抗病毒

* Corresponding author. E-mail: wxue@gzu.edu.cn

Received January 14, 2017; revised February 28, 2017; published online April 18, 2017.

Project supported by the National Natural Science Foundation of China (No. 21462012) and the Excellent Young Talents of Science and Technology in Gui-zhou Province (No. 201535).

国家自然科学基金(No. 21462012)和贵州省优秀青年科技人才(No. 201535)资助项目.

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有机化学

剂[1]、杀菌剂[2]、除草剂[3]、植物调节剂[4]、食品添加剂及抗癌药[5]等, 被广泛应用于工业、农业以及制药等行业.

黄酮醇类化合物作为生物体内的次生代谢物广泛分布于大自然中, 因其具有多种多样的生理活性而备受国内外重视[6]. 目前, 黄酮醇化合物的生物活性研究集中在心血管系统[7]、病毒[8]、炎症[9]和肿瘤[10]等方面, 关于黄酮化合物抗菌活性报道仅限于少数天然产物中分离的黄酮醇类化合物, 关于黄酮类化合物抗菌作用的系统研究未见报道, 针对农经作物上的常见植物细菌病害研究更是少见. 众所周知, 植物细菌病害造成的腐烂、畸形、枯萎、斑点和变色等影响农经作物的正常生长和品质, 威胁粮食安全. 当前, 化学杀菌剂是防治作物细菌的主要手段, 且品种比较单一, 防治作物细菌病害的有效途径有限且效果不理想[11,12]. 拼合原理是设计创新药物的重要思想, 目前已有许多成功的范例, 鉴于黄酮醇和亚磷酸酯的生物活性, 本工作拟设计合成以黄酮醇为结构骨架的磷酸酯类化合物, 研究它们的结构与活性关系, 以期获得较高抑制植物病菌的先导化合物. 作为一种尝试, 本工作将系列取代黄酮醇分别引入亚磷酸二乙酯, 设计合成了14个未见报道的取代黄酮磷酸酯类化合物2a～2n, 合成路线见Scheme 1. 采用浊度法[13,14]测试了目标化合物抗植物细菌活性, 发现部分化合物具有超过阳性对照物的活性, 验证了设计思想, 值得进一步研究.

1 结果与讨论

1.1 目标化合物的合成及结构表征

以系列黄酮醇和亚磷酸酯为原料, 三乙胺为催化剂, 四氯化碳为溶剂, 反应24 h, 合成系列取代黄酮磷酸二乙酯化合物. 在本研究中, 若以四氯化碳为溶剂、氨或其他无机碱作为催化剂时, 薄层色谱(TLC)跟踪发现反应副产物较多或不反应. 通过对反应条件的摸索, 我们发现以四氯化碳为溶剂, 三乙胺为催化剂, 最后能以较高收率得到目标化合物. 相应的反应机理为: 首先亚磷酸酯与三乙胺反应生成的亚磷酸酯负离子与四氯化碳反应生成氯代磷酸酯, 最后黄酮醇在三乙胺的催化下与反应过程中产生的氯代磷酸酯反应得到目标化合物, 由此可知, 三乙胺作为催化剂更有利于在反应过程中氯代磷酸酯的产生[15,16].

在IR中, 化合物2a～2n的P＝O的伸缩振动峰在1300～1250 cm－1左右, 黄酮骨架上酮羰基C＝O的振动峰在15～1603 cm－1. 在1H NMR中, 饱和碳上的质子化学位移位于δ 1.00～4.50范围内; 在13C NMR中, 饱和碳的化学位移均在高场区, 出现在δ 10.00～70.00之

间; 在31P NMR中, 2a～2n的P呈现单峰处于δ －4.00～－6.11范围内. 在ESI-MS中, 2a～2n均出现较强的[M＋H]＋和[M＋Na]＋峰. 在HRMS谱图中, 目标产物的HRMS [M＋H]＋实测值和理论计算值是一致的, 误差均在m/z ±0.003内, 进一步证实了目标化合物的结构.

1.2 目标化合物的抗植物病菌活性分析

目标化合物2a～2n的抗菌活性测试结果见表1. 从该表可知, 部分化合物在100 µg/mL浓度下对水稻白叶枯病菌表现出优良的抑制活性, 明显高于对照药剂噻菌铜(34.3%)和叶枯唑(57.4%). 部分化合物对柑橘溃疡病菌表现出一定的抑菌活性. 其中2h和2k在100 µg/mL浓度下对柑橘溃疡病菌的抑制率分别为85.1 %和71.7%.

以商品化的叶枯唑为对照药剂, 对化合物2b, 2e, 2f, 2k和2m进行了毒力回归方程和EC50值测试, 结果见表2. 从表2可知, 上述5个化合物对水稻白叶枯病菌的抑制率活性明显优于对照药剂叶枯唑. 其中, 化合物2f和2m对水稻白叶枯病菌的EC50值分别为22.78和16.47 µg/mL, 远低于叶枯唑的88.51 µg/mL.

初步构效关系分析表明, 当R2为甲氧基时, 不管是邻位单取代基还是对位单取代基, 在100和50 µg/mL两个供试浓度下, 化合物2a, 2b, 2e和2f对水稻白叶枯病菌的抑制率均较好, 进一步分析, 取代基R2为2'-OCH3的化合物2b和2f在100和50 µg/mL两个供试

Chin. J. Org. Chem. 2017, 37, 2145～2152

OOHO1a~1n

OHNaOH,ethanol,H2O2

HPO(OC2H5)2Et3N,CCl4

OOOPR2

OO2a~2n

a:R1=7-OCH3,R2=4'-OCH3;b:R1=7-OCH3,R2=2'-OCH3;c:R1=7-OCH3,R2=4'-CI;d:R1=7-OCH3,R2=4'-C(CH3)3;

e:R1=7-OCH2CH3,R2=4'-OCH3;f:R1=7-OCH2CH3,R2=2'-OCH3;g:R1=7-OCH2CH3,R2=2'-Br;h:R1=7-OCH2CH3,R2=4'-F;i:R1=7-OCH2CH3,R2=4'-CI;j:R1=7-OCH2CH3,R2=3'-Br;k:R1=7-OCH2CH3,R2=4'-CH3;l:R1=7-OCH2CH3,R2=H;m:R1=7-OCH2CH3,R2=3'-OCH3-4'-OCH3;n:R1=7-OCH2CH3,R2=2'-OCH3-4'-OCH3

图式1 目标化合物2a～2n的合成路线

Scheme 1 Synthetic route of target compounds 2a～2n

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表1 目标化合物2a～2n的抗细菌活性(抑制率/%)a

Table 1 Antibacterial activities (inhibition rate/%) of target compounds 2a～2n

Chinese Journal of Organic Chemistry

Xanthomonas oryzae pv. oryzae Xanthomonas axonopodis pv. citri

100 µg/mL 50 µg/mL 100 µg/mL 50 µg/mL

2a 55.0±3.8 44.5±1.2 8.2±1.4 2.8±1.1 2b 92.8±0.5 58.2±1.4 40.7±3.3 38.6±3.3 2c 49.3±4.4 12.8±3.0 42.6±2.1 22.9±1.6 2d 49.3±2.2 45.5±1.4 37.1±2.7 34.6±1.0 2e 61.4±3.7 56.6±1.6 23.4±1.8 20.3±2.6 2f 87.7±1.1 69.2±2.6 42.3±2.7 32.7±2.7 2g 14.4±2.0 12.7±3.2 44.5±3.1 40.9±1.8 2h 17.3±2.6 7.7±2.7 85.1±3.3 65.7±2.9 2i 44.3±1.4 22.8±2.1 60.7±1.9 41.3±2.8 2j 51.3±3.0 37.0±2.6 36.6±2.6 23.2±2.9 2k 74.4±2.0 53.5±3.9 71.7±2.1 48.9±1.7 2l 55.8±2.0 28.5±1.9 33.3±2.6 28.2±3.9 2m 88.3±1.7 .1±3.3 10.1±2.9 7.1±1.7 2n 35.7±3.1 26.1±2.1 43.3±1.4 36.5±1.2

Thiodiazole-copper 34.3±2.2 20.8±2.1 20.2±3.4 10.9±2.5 Bismerthiazolb 57.4±2.0 33.4±2.7 70.1±1.9 49.8±2.0

Compd.

Average of three replicates. b The commercial bactericides (thiodiazole-copper and bismerthiazol) were used for comparison of antibacterial activity.

表2 目标化合物2b, 2e, 2f, 2k和2m对水稻白叶枯病菌的抑制率

Table 2 Inhibitory effects of compounds 2b, 2e, 2f, 2k and 2m against Xanthomonas oryzae pv. Oryzae Compd. 2b 2e 2f 2k 2m

Bismerthiazolb

Toxic regression equation r

EC50/(µg•mL－1)

26.03 65.73 22.78 40.62 16.47 88.51

y＝1.8801＋2.2043x 0.9903 y＝2.61＋1.2580x 0.9927 y＝2.6020＋1.76x 0.9694 y＝2.4165＋1.6059x 0.9975 y＝1.9605＋2.4980x 0.9969 y＝1.9605＋2.4980x 0.9800

核磁共振仪测定(TMS为内标或85%的H3PO4为外标, CDCl3或DMSO-d6为溶剂); 质谱由Agilent 1100 MSD- Trap-VL质谱仪测定; 高分辨质谱采用美国Thermofisher公司Q Exactive型液质联用仪; IR由Shimadzu Prestige-21型红外光谱仪测定(KBr压片); 熔点用X-4数字型熔点仪测定(温度计未经校正). 4-甲氧基-2-羟基苯乙酮、4-乙氧基-2-羟基苯乙酮和亚磷酸二乙酯购自上海泰坦科技股份有限公司, 其他试剂均为市售分析纯或化学纯.

3.2 中间体及目标化合物的合成

3.2.1 中间体取代黄酮醇1a～1n的合成方法向50 mL圆底烧瓶中加入取代2-羟基苯乙酮(1.66 mmol)、取代苯甲醛(1.66 mmol)及氢氧化钠(3.00 mmol), 以乙醇(20 mL)为溶剂, 常温搅拌, 用TLC检测至反应不再发生变化. 继续将反应物冷却到0 ℃, 加入氢氧化钠(2.00 mmol)和30%双氧水(2.20 mmol), 搅拌30 min后逐渐升至室温并继续搅拌12, 然后TLC跟踪反应不再发生变化. 将反应物倒入冰水中, 在搅拌下加入6 mol/L的盐酸调节pH值至酸性, 析出大量固体, 滤出固体, 并用纯净水(30 mL)冲洗3次, 用硅胶柱色谱纯化得到取代黄酮醇[17].

4',7-二甲氧基黄酮醇(1a): 黄色固体, 收率63%. m.p. 192～194 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.23～8.15 (m, 2H), 8.11 (d, J＝8.9 Hz, 1H), 7.05～7.01 (m, 2H), 7.00 (d, J＝0.8 Hz, 1H), 6.97 (dd, J＝8.9, 2.3 Hz, 1H), 6.93 (d, J＝2.3 Hz, 1H), 3.92 (s, 3H), 3.88 (d, J＝2.7 Hz, 3H); HRMS calcd for C17H15O5 [M＋H]＋ 299.09140,

Average of three replicates. b The commercial bactericides agent (bismerthia-zol) was used for comparison of antibacterial activity.

浓度下对水稻白叶枯病菌的抑制活性整体要优于取代基R2为4'-OCH3的化合物2a和2e, 其中化合物2b在100 µg/mL浓度下对水稻白叶枯病菌抑制率达到92.8%. 当R2为对氟取代基时, 化合物2h在100和50 µg/mL两个供试浓度下对柑橘溃疡病菌的抑制活性均优于苯环上其他取代基的化合物, 这可能是氟原子具有较小的体积及其特殊的生物效应所致.

2 结论

通过条件探索, 成功设计合成了取代黄酮磷酸二乙酯目标化合物14个; 并进行了抗植物病菌活性测试, 发现了对水稻白叶枯病菌和柑橘溃疡病菌表现出较好活性的新化合物, 为后续研究奠定了基础.

3 实验部分

3.1 仪器与试剂

H NMR, 13C NMR, 31P NMR由JEOL ECX-500型

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found 299.09103.

2',7-二甲氧基黄酮醇(1b): 黄色固体, 收率58%. m.p. 204～206 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.16 (d, J＝9.0 Hz, 1H), 7.57 (dd, J＝7.6, 1.6 Hz, 1H), 7.52～7.40 (m, 1H), 7.10 (td, J＝7.5, 0.7 Hz, 1H), 7.06 (d, J＝8.3 Hz, 1H), 6.99 (dd, J＝9.0, 2.3 Hz, 1H), 6.88 (d, J＝2.3 Hz, 1H), 6.47 (s, 1H), 3. (s, 3H), 3.87 (s, 3H); HRMS calcd for C16H12O4Cl [M＋H]＋ 303.04186, found 303.04153.

4'-氯-7-甲氧基黄酮醇(1c): 黄色固体, 收率71%. m.p. 174～176 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.23～8.15 (m, 2H), 8.13 (d, J＝8.9 Hz, 1H), 7.55～7.42 (m, 2H), 7.23～7.05 (m, 1H), 7.00 (dd, J＝8.9, 2.3 Hz, 1H), 6.94 (d, J＝2.3 Hz, 1H), 3.94 (s, 3H); HRMS calcd for C16H12O4Cl [M＋H]＋ 303.04186, found 303.04153.

4'-叔丁基-7-甲氧基黄酮醇(1d): 黄色固体, 收率40%. m.p. 192～194 ℃; 1H NMR (500 MHz, DMSO-d6) δ: 9.36 (s, 1H), 8.23～8.01 (m, 2H), 7.97 (d, J＝8.9 Hz, 1H), 7.68～7.42 (m, 2H), 7.23 (d, J＝2.4 Hz, 1H), 7.02 (dd, J＝8.9, 2.4 Hz, 1H), 3. (s, 3H), 1.30 (s, 9H); HRMS calcd for C20H21O4 [M＋H]＋ 325.14344, found 325.14282.

4'-甲氧基-7-乙氧基黄酮醇(1e): 黄色固体, 收率60%. m.p. 162～1 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.20 (d, J＝8.5 Hz, 2H), 8.11 (d, J＝8.9 Hz, 1H), 7.04 (d, J＝8.4 Hz, 2H), 6.97 (d, J＝8.7 Hz, 2H), 6.92 (s, 1H), 4.15 (d, J＝6.8 Hz, 2H), 3. (s, 3H), 1.49 (t, J＝6.7 Hz, 3H); HRMS calcd for C18H17O5 [M＋H]＋ 313.10705, found 313.10651.

2'-甲氧基-7-乙氧基黄酮醇(1f): 黄色固体, 收率53%. m.p. 171～172 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.15 (d, J＝8.9 Hz, 1H), 7.56 (d, J＝7.6 Hz, 1H), 7.52～7.43 (m, 1H), 7.10 (t, J＝7.5 Hz, 1H), 7.06 (d, J＝8.4 Hz, 1H), 7.00～6.94 (m, 1H), 6.86 (d, J＝2.2 Hz, 1H), 6.43 (s, 1H), 4.11 (q, J＝7.0 Hz, 2H), 3.88 (s, 3H), 1.46 (t, J＝7.0 Hz, 3H); HRMS calcd for C18H17O5 [M＋H]＋ 313.10705, found 313.105.

2'-溴-7-乙氧基黄酮醇(1g): 黄色固体, 收率63%. m.p. 149～151 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.21 (d, J＝15.4 Hz, 1H), 7.79 (d, J＝8.8 Hz, 1H), 7.72 (dd, J＝7.8, 1.6 Hz, 1H), 7. (dd, J＝8.0, 1.1 Hz, 1H), 7.50 (d, J＝15.4 Hz, 1H), 7.41～7.31 (m, 1H), 7.28～7.22 (m, 1H), 6.45 (t, J＝2.4 Hz, 1H), 4.09 (q, J＝7.0 Hz, 2H), 1.44 (t, J＝7.0 Hz, 3H); HRMS calcd for C17H14O4Br [M＋H]＋ 361.00700, found 361.00659.

4'-氟-7-乙氧基黄酮醇(1h): 黄色固体, 收率71%.

m.p. 162～1 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.23 (dd, J＝8.7, 5.4 Hz, 2H), 8.11 (d, J＝8.9 Hz, 1H), 7.20 (t, J＝8.6 Hz, 2H), 7.11 (s, 1H), 6.97 (dd, J＝8.9, 2.0 Hz, 1H), 6.91 (d, J＝2.0 Hz, 1H), 4.14 (q, J＝7.0 Hz, 2H), 1.49 (t, J＝7.0 Hz, 3H); HRMS calcd for C17H14O4F [M＋H]＋ 301.08706, found 301.08676.

4'-氯-7-乙氧基黄酮醇(1i): 黄色固体, 收率75%. m.p. 170～172 ℃; 1H NMR (500 MHz, DMSO-d6) δ: 9.68 (s, 1H), 8.21 (d, J＝8.5 Hz, 2H), 7.95 (d, J＝8.9 Hz, 1H), 7.60 (d, J＝8.5 Hz, 2H), 7.23 (s, 1H), 7.07～6.85 (m, 1H), 4.16 (dd, J＝13.7, 6.8 Hz, 2H), 1.36 (t, J＝6.8 Hz, 3H); HRMS calcd for C17H14O4Cl [M＋H]＋ 317.05751, found 317.05701.

3'-溴-7-乙氧基黄酮醇(1j): 黄色固体, 收率72%. m.p. 175～177 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.35 (t, J＝1.8 Hz, 1H), 8.25～8.18 (m, 1H), 8.11 (d, J＝8.9 Hz, 1H), 7.57 (dd, J＝8.0, 1.9, 1H), 7.39 (t, J＝8.0 Hz, 1H), 7.15 (d, J＝34.2 Hz, 1H), 6.99 (dd, J＝8.9, 2.3 Hz, 1H), 6.94 (d, J＝2.3 Hz, 1H), 4.16 (q, J＝7.0 Hz, 2H), 1.50 (t, J＝7.0 Hz, 3H); HRMS calcd for C17H14O4Br [M＋H]＋ 361.00700, found 361.00662.

4'-甲基-7-乙氧基黄酮醇(1k): 黄色固体, 收率51%. m.p. 174～176 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.20～8.06 (m, 3H), 7.32 (d, J＝8.1 Hz, 2H), 7.00 (s, 1H), 6.97 (dd, J＝8.9, 1.9 Hz, 1H), 6.92 (d, J＝2.0 Hz, 1H), 4.14 (q, J＝6.9 Hz, 2H), 2.43 (s, 3H), 1.49 (t, J＝6.9 Hz, 3H); HRMS calcd for C18H17O4 [M＋H]＋ 297.11214, found 297.11188.

7-乙氧基黄酮醇(1l): 黄色固体, 收率60%. m.p. 157～159 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.28～8.18 (m, 2H), 8.12 (d, J＝8.9 Hz, 1H), 7.53 (t, J＝7.6 Hz, 2H), 7.46 (d, J＝7.3 Hz, 1H), 7.03 (s, 1H), 6.98 (dd, J＝8.9, 2.2 Hz, 1H), 6.93 (d, J＝2.2 Hz, 1H), 4.15 (q, J＝7.0 Hz, 2H), 1.49 (t, J＝7.0 Hz, 3H); HRMS calcd for C17H15O4 [M＋H]＋ 283.099, found 283.09622.

3',4'-二甲氧基-7-乙氧基黄酮醇(1m): 黄色固体, 收率47%. m.p. 165～167 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.11 (d, J＝8.9 Hz, 1H), 7.84 (dd, J＝8.5, 2.0 Hz, 1H), 7.81 (d, J＝2.0 Hz, 1H), 7.01 (d, J＝8.6 Hz, 1H), 6.99 (d, J＝2.3 Hz, 1H), 6.97 (d, J＝2.3 Hz, 1H), 6.92 (d, J＝2.2 Hz, 1H), 4.15 (t, J＝7.0 Hz, 2H), 3.99 (s, 3H), 3.96 (s, 3H), 1.49 (t, J＝7.0 Hz, 3H); HRMS calcd for C19H19O6 [M＋H]＋ 343.11761, found 343.11691.

2',4'-二甲氧基-7-乙氧基黄酮醇(1n): 黄色固体, 收率56%. m.p. 177～179 ℃; 1H NMR (500 MHz, CDCl3)

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δ: 8.12 (d, J＝15.5 Hz, 1H), 7.80 (d, J＝8.8 Hz, 1H), 7.60 (d, J＝15.5 Hz, 1H), 7.56 (d, J＝8.6 Hz, 1H), 6.53 (dd, J＝8.6, 2.3 Hz, 1H), 6.47 (dd, J＝6.0, 2.4 Hz, 1H), 6.44 (t, J＝2.3 Hz, 1H), 4.08 (q, J＝7.0 Hz, 2H), 3.91 (s, 3H), 3.86 (s, 3H), 1.43 (t, J＝7.0 Hz, 3H); HRMS calcd for C19H19O6 [M＋H]＋ 343.11707, found 343.11691.

1256, 1207, 1015, 836 cm－1; ESI-MS m/z: 435.2 ([M＋

H]＋), 457.1 ([M＋Na]＋); HRMS calcd for C21H24O8P [M＋H]＋ 435.12033, found 435.11945.

O,O'-二乙基-O''-(4'-氯-7-甲氧基黄酮-3-基)磷酸酯(2c): 黄色固体, 收率90%. m.p. 101～103 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.11 (d, J＝8.8 Hz, 1H, ArH), 7.90 (s, 1H, ArH), 7.88 (s, 1H, ArH), 7.47 (s, 1H, ArH), 7.45 (s, 3.2.2 目标化合物的合成 1H, ArH), 6.95 (dd, J＝8.8, 2.3 Hz, 1H, ArH), 6.85 (d, J＝在50 mL单口烧瓶内加入化合物1 (1.00 mmol)、四

2.3 Hz, 1H, ArH), 4.28～4.06 [m, 4H, P(OCH2CH3)2], 3.87 氯化碳(30 mL)和三乙胺(3.00 mmol), 室温搅拌0.5 h使

(s, 3H, ArOCH3), 1.24 [td, J＝7.1, 1.1 Hz, 6H, 其溶解, 然后在冰浴条件下滴加含四氯化碳(6 mL)和H-P(OCH2CH3)2]; 13C NMR (125 MHz, CDCl3) δ: 172.14 , 亚磷酸二乙酯(4.00 mmol)的混合溶液, 搅拌30 min. 氮

1.50, 157.15, 1.11, 137.24, 134.41, 130.34, 128.80, 气保护下室温搅拌24 h后TLC监测至新点产生及原料

128.72, 127.48, 117.62, 114.93, 100.07, .97, .92, 点不再变化, 用乙酸乙酯萃取(30 mL×3), 用0.5 mol/L

55.98, 16.13, 16.07; 31P NMR (202 MHz, CDCl3) δ: －盐酸溶液冲洗(15 mL×3), 用0.5%氢氧化钠溶液中和

4.41; IR (KBr) ν: 2980, 1615, 1496, 1440, 1250, 1170, (15 mL×3)和无水硫酸钠干燥后, 减压蒸馏得到粗品,

1026, 840 cm－1; ESI-MS m/z: 439.1 ([M＋H]＋), 461.1 用硅胶柱层析[V(石油醚)∶V(乙酸乙酯)＝1∶1]得到化

([M＋Na]＋); HRMS calcd for C20H21ClO7P [M＋H]＋合物2.

439.07079, found 439.07016. O,O'-二乙基-O''-(4',7-二甲氧基黄酮-3-基)磷酸酯

O,O'-二乙基-O''-(4'-叔丁基-7-甲氧基黄酮-3-基)磷(2a): 黄色固体, 收率88%. m.p. 77～79 ℃; 1H NMR

酸酯(2d): 黄色固体, 收率63%. m.p. 61～63 ℃; 1H (500 MHz, DMSO-d6) δ: 7.96 (d, J＝8.8 Hz, 1H, ArH),

NMR (500 MHz, CDCl3) δ: 8.10 (d, J＝8.8 Hz, 1H, ArH), 7.90 (s, 1H, ArH), 7. (s, 1H, ArH), 7.24 (s, 1H, ArH),

7.83 (d, J＝8.2 Hz, 2H, 2×ArH), 7.49 (d, J＝8.2 Hz, 2H, 7.13 (s, 1H, ArH), 7.11 (s, 1H, ArH), 7.07 (d, J＝10.7 Hz,

2×ArH), 6.91 (d, J＝8.6 Hz, 1H, ArH), 6.83 (s, 1H, ArH), 1H, ArH), 4.11～3.93 [m, 4H, P(OCH2CH3)2], 3.88 (s, 3H,

4.07 [dd, J＝7.1, 2.6 Hz, 4H, P(OCH2CH3)2], 3.83 (s, 3H, ArOCH3), 3.82 (s, 3H, ArOCH3), 1.18～1.07 [m, 6H,

ArOCH3), 1.31 [s, 9H, Ar(CH3)3], 1.17 [t, J＝7.0 Hz, 6H, P(OCH2CH3)2]; 13C NMR (125 MHz, DMSO-d6) δ:

P(OCH2CH3)2]; 13C NMR (125 MHz, CDCl3) δ: 172.25, 171.59, 1.60, 162.04, 157.10, 155.46, 133., 131.01,

1.32, 157.23, 155.74, 1.58, 134.18, 134.13, 128.81, 126.97, 122.15, 117.19, 115.61, 114.61, 101.23, .76,

127.38, 125.45, 117.69, 114.68, 100.11, .72, .67, .71, 56.73, 56.06, 16.38, 16.32; 31P NMR (202 MHz,

55.91, 35.04, 31.21, 16.07, 16.01; 31P NMR (202 MHz, DMSO-d6) δ: －4.37; IR (KBr) ν: 2983, 1638, 1515, 1444,

CDCl3) δ: －4.41; IR (KBr) ν: 2961, 18, 1441, 1259, 1256, 1201, 1016, 845 cm－1; ESI-MS m/z: 435.2 ([M＋

－1

H]＋), 457.1 ([M＋Na]＋); HRMS calcd for C21H24O8P 1173, 1035, 993, 845 cm; ESI-MS m/z: 461.2 ([M＋

H]＋), 483.2 ([M＋Na]＋); HRMS calcd for C24H30O7P [M＋H]＋ 435.12033, found 435.11966.

[M＋H]＋ 461.17237, found 461.17148. O,O'-二乙基-O''-(2',7-二甲氧基黄酮-3-基)磷酸酯

O,O'-二乙基-O''-(4'-甲氧基-7-乙氧基黄酮-3-基)磷(2b): 黄色油状, 收率74%; 1H NMR (500 MHz,

酸酯(2e): 黄色固体, 收率73%. m.p. 87～ ℃; 1H DMSO-d6) δ: 8.00 (d, J＝9.0 Hz, 1H, ArH), 7.56 (dd, J＝

NMR (500 MHz, CDCl3) δ: 8.11 (d, J＝8.9 Hz, 1H, ArH), 9.3, 8.3 Hz, 1H, ArH), 7.48 (dd, J＝7.5, 1.6 Hz, 1H, ArH),

7.93 (s, 1H, ArH), 7.91 (s, 1H, ArH), 7.00 (s, 1H, ArH), 7.20 (d, J＝8.4 Hz, 1H, ArH), 7.18 (d, J＝2.3 Hz, 1H,

6.99 (s, 1H, ArH), 6.93 (d, J＝8.9 Hz, 1H, ArH), 6.84 (s, ArH), 7.11 (d, J＝2.2 Hz, 1H, ArH), 7.10～7.07 (m, 1H,

1H, ArH), 4.25～4.05 [m, 6H, P(OCH2CH3)2, ArH), 3.93～3.69 [m, 10H, P(OCH2CH3)2, ArOCH3,

ArOCH2CH3], 3.86 (s, 3H, ArOCH3), 1.45 (t, J＝6.9 Hz, ArOCH3], 1.04 [dt, J＝7.6, 3.8 Hz, 6H, P(OCH2CH3)2];

133H, ArOCH2CH3), 1.24 [t, J＝7.0 Hz, 6H, P(OCH2CH3)2]; C NMR (125 MHz, DMSO-d6) δ: 171.52, 1.71,

C NMR (125 MHz, CDCl3) δ: 172.26, 163.66, 161.73, 157.66, 157.61, 155.66, 135.09, 133.30, 131.33, 127.07,

157.13, 155.31, 133.78, 130.71, 127.37, 122.57, 117.50, 120.84, 118.87, 117.48, 115.83, 112.43, 101.20, .42,

114.97, 113.91, 100.49, .85, .81, .35, 55.55, 16.16, .37, 56.78, 56.41, 16.29, 16.24; 31P NMR (202 MHz,

16.10, 14.65; 31P NMR (202 MHz, CDCl3) δ: －4.30; IR DMSO-d6) δ: -5.08; IR (KBr) ν: 2982, 1627, 1492, 1445,

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(KBr) ν: 2983, 1623, 1443, 1259, 1185, 1032, 968, 843 cm－1; ESI-MS m/z: 449.2 ([M＋H]＋), 471.1 ([M＋Na]＋); HRMS calcd for C22H26O8P [M＋H]＋ 449.13598, found 449.13522.

O,O'-二乙基-O''-(2'-甲氧基-7-乙氧基黄酮-3-基)磷酸酯(2f): 黄色固体, 收率73%. m.p. 87～ ℃; 1H NMR (500 MHz, CDCl3) δ: 8.09 (d, J＝9.0 Hz, 1H, ArH), 7.49 (d, J＝7.5 Hz, 1H, ArH), 7.43 (t, J＝8.8 Hz, 1H, ArH), 7.01 (t, J＝7.4 Hz, 1H, ArH), 6.96 (d, J＝8.4 Hz, 1H, ArH), 6.90 (dd, J＝8.8, 2.2 Hz, 1H, ArH), 6.76 (d, J＝2.1 Hz, 1H, ArH), 4.02 (q, J＝7.0 Hz, 2H, ArOCH2CH3), 3.99～3.90 [m, 4H, P(OCH2CH3)2], 3.78 (s, 3H, ArOCH3), 1.37 (t, J＝6.9 Hz, 3H, ArOCH2CH3), 1.12 [td, J＝7.2, 0.9 Hz, 6H, P(OCH2CH3)2]; 13C NMR (125 MHz, CDCl3) δ: 172.09, 163.56, 157.59, 157., 155.23, 135.23, 132.35, 131.07, 127.18, 120.36, 119.26, 117.75, 115.01, 111.40, 100., .41, .27, .20, 55.84, 16.01, 15.94, 14.53; 31P NMR (202 MHz, CDCl3) δ: －4.10; IR (KBr) ν: 2981, 1614, 1465, 1444, 1248, 1182, 1032, 987 cm－1; ESI-MS m/z: 449.2 ([M＋H]＋), 471.1 ([M＋Na]＋); HRMS calcd for C22H26O8P [M＋H]＋ 449.13598, found 449.13498.

O,O'-二乙基-O''-(2'-溴-7-乙氧基黄酮-3-基)磷酸酯(2g): 黄色固体, 收率56%. m.p. 90～92 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.16 (d, J＝8.9 Hz, 1H, ArH), 7.72 (d, J＝8.0 Hz, 1H, ArH), 7.67 (d, J＝7.5 Hz, 1H, ArH), 7.46 (t, J＝7.5 Hz, 1H, ArH), 7.39 (t, J＝7.7 Hz, 1H, ArH), 6.98 (d, J＝9.1 Hz, 1H, ArH), 6.83 (s, 1H, ArH), 4.10 (q, J＝7.0 Hz, 2H, ArOCH2CH3), 4.02 [p, J＝7.1 Hz, 4H, P(OCH2CH3)2], 1.45 (t, J＝7.0 Hz, 3H, ArOCH2CH3), 1.18 [t, J＝7.1 Hz, 6H, P(OCH2CH3)2]; 13C NMR (125 MHz, CDCl3) δ: 172.23, 163.90, 157.53, 155.85, 134.99, 133.07, 132.13, 132.01, 131.63, 127.45, 127.39, 123.24, 117.93, 115.37, 100.63, .75, .70, .39, 16.04, 15.97, 14.62; 31

P NMR (202 MHz, CDCl3) δ: －5.21; IR (KBr) ν: 2982, 15, 1446, 1248, 1183, 1034, 986, 836 cm－1; ESI-MS m/z: 497.1 ([M＋H]＋), 521.1 ([M＋Na]＋); HRMS calcd for C21H23BrO7P [M＋H]＋ 497.03593, found 497.034.

O,O'-二乙基-O''-(4'-氟-7-乙氧基黄酮-3-基)磷酸酯 (2h): 黄色固体, 收率90%. m.p. 74～76 ℃; 1H NMR (500 MHz, DMSO-d6) δ: 7.97 (dd, J＝8.7, 5.8 Hz, 3H, 3×ArH), 7.44 (t, J＝8.8 Hz, 2H, 2×ArH), 7.23 (d, J＝2.1 Hz, 1H, ArH), 7.07 (dd, J＝8.9, 2.1 Hz, 1H, ArH), 4.16 (q, J＝6.9 Hz, 2H, ArOCH2CH3), 4.08～3.90 [m, 4H, P(OCH2CH3)2], 1.35 (t, J＝6.9 Hz, 3H, ArOCH2CH3), 1.11 [t, J＝7.0 Hz, 6H, P(OCH2CH3)2]; 13C NMR (125 MHz, DMSO-d6) δ: 171., 165.09, 163.98, 163.10, 157.22, 1.76, 133.96, 132.03, 131.96, 127.01, 126.63, 117.12, 116.44, 116.26, 116.08, 101.66, .91, .82, .77, 16.34, 16.28, 14.87; 31P NMR (202 MHz, DMSO-d6) δ: －4.46; IR (KBr) ν: 2984, 17, 1507, 1446, 1258, 1187, 1037, 840 cm－1; ESI-MS m/z: 437.1 ([M＋H]＋), 459.1 ([M＋ Na]＋); HRMS calcd for C21H23FO7P [M＋H]＋ 437.11599, found 437.11502.

O,O'-二乙基-O''-(4'-氯-7-乙氧基黄酮-3-基)磷酸酯(2i): 黄色固体, 收率72%. m.p. 82～84 ℃; 1H NMR (500 MHz, DMSO-d6) δ: 7.97 (d, J＝8.8 Hz, 1H, ArH), 7.94 (s, 1H, ArH), 7.92 (s, 1H, ArH), 7.67 (s, 1H, ArH), 7.66 (s, 1H, ArH), 7.23 (s, 1H, ArH), 7.07 (d, J＝7.3 Hz, 1H, ArH), 4.17 (q, J＝6.8 Hz, 2H, ArOCH2CH3), 4.09～3.93 [m, 4H, P(OCH2CH3)2], 1.35 (t, J＝6.9 Hz, 3H, ArOCH2CH3), 1.11 [t, J＝7.0 Hz, 6H, P(OCH2CH3)2]; 13C NMR (125 MHz, DMSO-d6) δ: 171.60, 1.02, 157.21, 1.45, 136.63, 134.14, 131.11, 129.31, 128.93, 127.00, 117.11, 116.13, 101.62, .92, .87, .82, 16.32, 16.27, 14.87; 31P NMR (202 MHz, DMSO-d6) δ: －4.53; IR (KBr) ν: 2982, 1653, 1443, 1260, 11, 1094, 967, 840 cm－1; ESI-MS m/z: 453.2 ([M＋H]＋), 475.1 ([M＋Na]＋); HRMS calcd for C21H23ClO7P [M＋H]＋ 453.084, found 453.08572.

O,O'-二乙基-O''-(3'-溴-7-乙氧基黄酮-3-基)磷酸酯 (2j): 黄色固体, 收率87%. m.p. 63～65 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.11 (d, J＝8.8 Hz, 1H, ArH), 8.09 (s, 1H, ArH), 7.88 (d, J＝7.5 Hz, 1H, ArH), 7.62 (d, J＝7.8 Hz, 1H, ArH), 7.37 (t, J＝7.7 Hz, 1H, ArH), 6.95 (d, J＝8.9 Hz, 1H, ArH), 6.86 (s, 1H, ArH), 4.19 [td, J＝12.8, 5.9 Hz, 4H, P(OCH2CH3)2], 4.11 (dd, J＝13.3, 6.5 Hz, 2H, ArOCH2CH3), 1.45 (t, J＝6.5 Hz, 3H, ArOCH2CH3), 1.26 [t, J＝7.0 Hz, 6H, P(OCH2CH3)2]; 13C NMR (125 MHz, CDCl3) δ: 172.17, 163.95, 157.19, 153.56, 134.68, 133.90, 132.23, 131.76, 130.06, 127.59, 127.44, 122.51, 117.44, 115.41, 100.46, 65.05, 65.01, .46, 16.16, 16.10, 14.62; 31

P NMR (202 MHz, CDCl3) δ: －4.56; IR (KBr) ν: 2983, 1653, 1445, 1386, 1255, 1204, 1033, 842 cm－1; ESI-MS m/z: 499.1 ([M＋H]＋), 519.1 ([M＋Na]＋); HRMS calcd for C21H23BrO7P [M＋H]＋ 497.03593, found 497.03537.

O,O'-二乙基-O''-(4'-甲基-7-乙氧基黄酮-3-基)磷酸酯(2k): 黄色固体, 收率%. m.p. 86～88 ℃; 1H NMR (500 MHz, DMSO-d6) δ: 7.96 (d, J＝8.3 Hz, 1H, ArH), 7.81 (d, J＝6.4 Hz, 2H, 2×ArH), 7.38 (d, J＝6.8 Hz, 2H, 2×ArH), 7.22 (s, 1H, ArH), 7.06 (d, J＝7.7 Hz, 1H, ArH),

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Chinese Journal of Organic Chemistry

4.16 (s, 2H, ArOCH2CH3), 4.08～3.88 [m, 4H, P(OCH2CH3)2], 2.38 (s, 3H, ArCH3), 1.35 (s, 3H, ArOCH2CH3), 1.11 [t, J＝6.9 Hz, 6H, P(OCH2CH3)2]; 13C NMR (125 MHz, DMSO-d6) δ: 171., 163.92, 157.19, 155.59, 141.95, 133.93, 129.69, 129.14, 127.26, 126.98, 117.11, 115.98, 101.60, ., .74, .70, 21.62, 16.34, 16.28, 14.88; 31P NMR (202 MHz, DMSO-d6) δ: －4.48; IR (KBr) ν: 2969, 1637, 1608, 1361, 1269, 1227, 1025, 987cm－1; ESI-MS m/z: 433.2 ([M＋H]＋), 455.1 ([M＋ Na]＋); HRMS calcd for C22H26O7P [M＋H]＋ 433.14107, found 433.13983.

O,O'-二乙基-O''-(7-乙氧基黄酮-3-基)磷酸酯 (2l): 黄色固体, 收率77%. m.p. 61～63 ℃; 1H NMR (500 MHz, CDCl3) δ: 8.13 (d, J＝8.8 Hz, 1H, ArH), 7.96～7.86 (m, 2H, 2×ArH), 7.～7.45 (m, 3H, 3×ArH), 6.95 (d, J＝8.9 Hz, 1H, ArH), 6.85 (s, 1H, ArH), 4.22～3.94 [m, 6H, P(OCH2CH3)2, ArOCH2CH3], 1.45 (t, J＝6.9 Hz, 3H, ArOCH2CH3), 1.21 [t, J＝7.0 Hz, 6H, P(OCH2CH3)2]; 13C NMR (125 MHz, CDCl3) δ: 172.32, 163.79, 157.28, 155.51, 134.38, 131.00, 130.36, 129.03, 128.50, 127.43, 117.58, 115.15, 100.53, .80, .76, .38, 16.10, 16.04, 14.62; 31P NMR (202 MHz, CDCl3) δ: －4.45; IR (KBr) ν: 2984, 1627, 1450, 1256, 1188, 1031, 969, 838 cm－1; ESI-MS m/z: 419.2 ([M＋H]＋), 441.1 ([M＋Na]＋); HRMS calcd for C21H24O7P [M＋H]＋ 419.122, found 419.12463.

O,O'-二乙基-O''-(3',4'-二甲氧基-7-乙氧基黄酮-3-基)磷酸酯(2m): 黄色固体, 收率53%. m.p. 77～79 ℃; 1

H NMR (500 MHz, CDCl3) δ: 8.13 (d, J＝9.0 Hz, 1H, ArH), 7.58 (dd, J＝8.4, 2.0 Hz, 1H, ArH), 7.53 (d, J＝2.0 Hz, 1H, ArH), 6.97 (d, J＝8.5 Hz, 1H, ArH), 6.95 (d, J＝9.0 Hz, 1H, ArH), 6.86 (d, J＝2.2 Hz, 1H, ArH), 4.25～4.08 [m, 6H, P(OCH2CH3)2, ArOCH2CH3], 3.95 (d, J＝6.8 Hz, 6H, ArOCH3, ArOCH3), 1.46 (t, J＝7.0 Hz, 3H, ArOCH2CH3), 1.25 [td, J＝7.1, 0.9 Hz, 6H, P(OCH2- CH3)2]; 13C NMR (125 MHz, CDCl3) δ: 172.22, 163.69, 157.09, 155.18, 151.32, 148.69, 133.87, 127.37, 122.66, 122.53, 117.46, 114.96, 111.87, 110.70, 100.53, .87, .82, .37, 56.17, 56.11, 16.15, 16.09, 14.63; 31P NMR (202 MHz, CDCl3) δ: －4.15; IR (KBr) ν: 2982, 1626, 1516, 1269, 1188, 1034, 1025 cm－1; ESI-MS m/z: 479.2 ([M＋H]＋), 501.2 ([M＋Na]＋); HRMS calcd for C23H28O9P [M＋H]＋ 479.14655, found 479.14590.

O,O'-二乙基-O''-(2',4'-二甲氧基-7-乙氧基黄酮-3-基)磷酸酯(2n): 黄色固体, 收率66%. m.p. ～66 ℃;

Chin. J. Org. Chem. 2017, 37, 2145～2152

H NMR (500 MHz, CDCl3) δ: 8.11 (d, J＝9.0 Hz, 1H,

ArH), 7.45 (d, J＝8.4 Hz, 1H, ArH), 6.92 (dd, J＝9.1, 2.3 Hz, 1H, ArH), 6.78 (d, J＝2.2 Hz, 1H, ArH), 6.57 (dd, J＝8.5, 2.2 Hz, 1H, ArH), 6.52 (d, J＝2.2 Hz, 1H, ArH), 4.12～3.97 [m, 6H, P(OCH2CH3)2, ArOCH2CH3], 3.83 (s, 3H, ArOCH3), 3.79 (s, 3H, ArOCH3), 1.41 (t, J＝7.0 Hz, 3H, ArOCH2CH3), 1.18 [td, J＝7.1, 0.8 Hz, 6H, P(OCH2CH3)2]; 13C NMR (125 MHz, CDCl3) δ: 172.22, 163.52, 163.25, 159.07, 157., 155.40, 135.32, 132.13, 127.31, 117.86, 114.91, 112.18, 104.68, 100.59, 98.77, .51, .47, .27, 55.88, 55.66, 16.08, 16.02, 14.61; 31P NMR (202 MHz, CDCl3) δ: －4.91; IR (KBr) ν: 2978, 18, 1284, 1250, 1172, 1027, 838 cm－1; ESI-MS m/z: 479.2 ([M＋H]＋), 501.2 ([M＋Na]＋); HRMS calcd for C23H28O9 P [M＋H]＋479.14655, found 479.14575. 3.3 抑菌活性测试

采用浊度法, 以水稻白叶枯病菌(Xanthomonas oryzae pv. oryzae)和柑橘溃疡病菌(Xanthomonas axono-podis pv. citri)为测试对象, 以商品化药剂噻菌铜(Thiodiazole copper)和叶枯唑(Bismerthiazol)为阳性对照药剂, 在样品浓度为100和50 μg/mL 浓度下测试了目标化合物的离体抑菌活性.

将样品和对照药剂分别配制成浓度为100和50 μg/mL的含毒营养肉汤(nutrient broth)液体培养基分别置于试管中, 测定OD值, 该值为无菌培养基OD值. 然后接入受试菌种, 在28 ℃, 180 r/min恒温摇床振荡培养48 h, 将各个浓度的菌液在分光光度计上测定OD值, 该值即为含菌培养基的OD值. 按下式计算所测化合物的抑制率.

抑制率＝(校正后对照培养基菌液OD值－校正后含毒培养基OD值)/校正后对照培养基菌液OD值

校正OD值＝含菌培养基OD值－无菌培养基OD值

辅助材料(Supporting Information) 目标化合物的核磁共振图谱, ESI-MS和HRMS. 这些材料可以免费从本刊网站(http://sioc-journal.cn/)上下载.

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