林业科学  2017, Vol. 53 Issue (12): 93-101   PDF    
DOI: 10.11707/j.1001-7488.20171210
0

文章信息

陈智聪, 段文贵, 林桂汕, 张瑞, 罗梦香, 杨章旗
Chen Zhicong, Duan Wengui, Lin Guishan, Zhang Rui, Luo Mengxiang, Yang Zhangqi
桃金娘烯醛基噻唑-腙类化合物的合成及抑菌活性
Synthesis and Antifungal Activity of Novel Myrtenal-Based Thiazole-hydrazone Compounds
林业科学, 2017, 53(12): 93-101.
Scientia Silvae Sinicae, 2017, 53(12): 93-101.
DOI: 10.11707/j.1001-7488.20171210

文章历史

收稿日期：2016-09-05
修回日期：2016-11-03

作者相关文章

陈智聪
段文贵
林桂汕
张瑞
罗梦香
杨章旗

引用本文
陈智聪, 段文贵, 林桂汕, 张瑞, 罗梦香, 杨章旗. 2017. 桃金娘烯醛基噻唑-腙类化合物的合成及抑菌活性. 林业科学, 53(12): 93-101.
Chen Zhicong, Duan Wengui, Lin Guishan, Zhang Rui, Luo Mengxiang, Yang Zhangqi. 2017. Synthesis and Antifungal Activity of Novel Myrtenal-Based Thiazole-hydrazone Compounds. Scientia Silvae Sinicae, 53(12): 93-101.  DOI: 10.11707/j.1001-7488.20171210
桃金娘烯醛基噻唑-腙类化合物的合成及抑菌活性
陈智聪1, 段文贵1, 林桂汕1, 张瑞1, 罗梦香1, 杨章旗2    
1. 广西大学 南宁 530004;
2. 广西林业科学研究院 南宁 530002
收稿日期：2016-09-05; 修回日期：2016-11-03
基金项目：国家自然科学基金项目"新型桃金娘烯醛基生物活性化合物的合成及构效关系研究"（31460173）；八桂学者专项"松树资源培育及产业化关键技术创新"
通讯作者：段文贵
摘要：【目的】桃金娘烯醛可由可再生的α-蒎烯选择性氧化而得到，且本身具有多种生物活性。另外，含噻唑或腙亚结构化合物具有广泛的生物活性，常用于构建生物活性分子的砌块。本研究将噻唑和腙2类活性基团引入到桃金娘烯醛骨架中，合成得到系列新型桃金娘烯醛基噻唑-腙类生物活性化合物，为我国的天然优势林产资源α-蒎烯的改性和高值化利用提供新的途径。【方法】α-蒎烯经选择性烯丙位氧化得到桃金娘烯醛，然后与氨基硫脲缩合制备桃金娘烯醛缩氨基硫脲，再与一系列取代的α-溴代苯乙酮反应，合成得到16个桃金娘烯醛基噻唑-腙类化合物。通过FT-IR、1H-NMR、13C-NMR和ESI-MS等技术手段确认目标化合物的结构，并用琼脂稀释法测定对所合成的目标产物的抑菌活性。【结果】合成得到16个新型桃金娘烯醛基噻唑-腙类目标化合物4a-4p。测试4a-4p抑菌活性，在50 mg·L-1质量浓度下，目标化合物对水稻纹枯病菌、黄瓜枯萎病菌、花生褐斑病菌、玉米小斑病菌、苹果轮纹病菌、西瓜炭疽病菌、番茄早疫病菌和小麦赤霉病菌均具有一定的抑制活性。总体上，目标化合物对苹果轮纹病菌的抑制效果最好，有12个化合物的抑菌率大于60%，尤其是化合物4n（R=4-NO2），其抑菌率高达90.6%（活性级别为A级）。【结论】合成得到系列新型桃金娘烯醛基噻唑-腙类化合物。这些化合物均具有一定的抑菌活性，其中化合物4n（R=4-NO2）是值得进一步研究的先导化合物。
关键词：α-蒎烯    桃金娘烯醛    噻唑-腙    合成    抑菌活性    
Synthesis and Antifungal Activity of Novel Myrtenal-Based Thiazole-hydrazone Compounds
Chen Zhicong1, Duan Wengui1 , Lin Guishan1, Zhang Rui1, Luo Mengxiang1, Yang Zhangqi2    
1. Guangxi University Nanning 530004;
 2. Guangxi Academy of Forestry Nanning 530002
Abstract: 【Objective】Myrtenal can be derived by selective oxidation of α-pinene, which is renewable and abundant in China.Myrtenal has been found to exhibit various biological activities. The compounds containing thiazole orhydrazone moieties have been found to show a wide range of biological activities, and have been widely used as blocks for designing bioactive molecules. Therefore, a series of novel myrtenal-based thiazole-hydrazone bioactive compounds can be synthesized by incorporating both thiazole and hydrazone active blocks into the myrtenal skeleton with an attempt to provide a new pathway for the modification and high-value utilization of α-pinene which is a natural and preponderant forest resource in China.【Method】Myrtenal was prepared by the selectively allylic oxidation of α-pinene. Then, myrtenal-based thiosemicarbazone was prepared by the condensation reaction of myrtenal with thiosemicarbazide, followed by the reaction of myrtenal-based thiosemicarbazone with a series of substituted α-bromoacetophenones to yield sixteen myrtenal-based thiazole-hydrazone compounds 4a-4p which have not been reported in the literature. The molecular structures of the target compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR, and ESI-MS, and antifungal activity of the target products was evaluated by agar dilution method.【Result】Sixteen novel myrtenal-based thiazole-hydrazone target compounds were synthesized.At 50 mg·L-1, the antifungal activity test showed that all the target compounds exhibited to certain degree antifungal activity against Rhizoctonia solani, Fusarium oxysporum f. sp. cucumerinum, Cercospora arachidicola, Helminthosporium maydis, Physalospora piricola, olleetotrichum lagenarium, Alternaria solani, and Gibberella zeae. In total, the target compounds displayed the best antifungal activity against P.piricola, and there were twelve compounds with an inhibition rate of more than 60%, in particular, compound 4n (R=4-NO2)presented the best inhibition rate of 90.6% (A-class activity level).【Conclusion】A series of novel myrtenal-based thiazole-hydrazone compounds were synthesized. These compounds exhibited to certain degree antifungal activity, and among them compound 4n (R=4-NO2) was a leading compound worthy of deep research.
Key words: α-pinene    myrtenal    thiazole-hydrazone    synthesis    antifungal activity    

α-蒎烯是可再生性天然精油松节油的主要成分，利用α-蒎烯分子中的双键和四元环2个特征官能团以及烯丙位的反应，对其进行化学改性，合成得到多种功能性深加工产品(黄铎云等，2016)。桃金娘烯醛又名香桃木烯醛，天然存在于孜然芹(Cuminum cyminum)籽、桉(Eucalyptus spp.)叶、胡椒(Piper nigrum)和薄荷(Nepeta cataria)等精油中，主要用作香料以及有机合成中间体，将α-蒎烯的烯丙位甲基氧化可得到桃金娘烯醛(白雪等，2015；彭莉等，2013)。研究表明，桃金娘烯醛本身具有广泛的生物活性，如扩张支气管、抗炎、抗溶血、抗凝聚、抗菌(Vegezzi, 1980)、杀灭疟原虫(Kamchonwongpaisan et al., 1995)、抗肝癌(Lingaiah et al., 2013；Hari-Babu et al., 2012)和驱蚊(Hardie et al., 1994)等。

噻唑是含有1个氮原子和1个硫原子的五元芳性杂环。大量研究表明，该类化合物具有除草(Zaharia et al., 2010)、抗病毒、抗癌(李英俊等，2012)、抗炎(Rai et al., 2010；Helal et al., 2013)、杀虫(陈才俊等，2005)、抑菌(陈乃源等，2016)和镇痛(Kalkhambkar et al., 2007)等多样的生物活性，因此，噻唑环常用于构建生物活性分子的切块。腙类化合物分子结构中含有Schift碱和氨基活性基团(—CH＝N—NH—)，具有消炎(Kaplancikli et al., 2012)、抗病毒(Galayko et al., 2012)、抗菌(Osório et al., 2012)、抗肿瘤(Terzioglu et al., 2003)、杀虫(Wu et al., 2012；汪飞等，2006)和除草(康圣鸿等，2012)等生物活性。

结合本课题组近年来在松香、松节油、樟脑和樟脑酸等林产品基生物活性化合物方面所取得的研究成果(黄铎云等，2016；白雪等，2015；陈乃源等，2016；Duan et al., 2011；Lin et al., 2014；吴光燧等，2014；马献力等，2015)，本文通过对具有一定生物活性的桃金娘烯醛进行化学改性，合成得到系列含噻唑和腙活性基团的新型桃金娘烯醛基噻唑-腙类化合物，采用多种现代波谱手段对目标产物进行结构表征，并测试其抑菌活性，为我国天然优势林产资源α-蒎烯的化学改性和高值化利用提供新途径。

1 材料与方法 1.1 主要仪器与试剂

Nicolet iS 50 FT-IR红外光谱仪，美国Thermo Scientific有限公司；Avance Ⅲ HD 600 MHz超导核磁共振仪，瑞士Bruker有限公司；TSQ Quantum Access MAX液相色谱-质谱联用仪，美国Thermo Scientific有限公司；Agilent 6890气相色谱仪，美国Agilent Technologies有限公司；Waters 1525高效液相色谱仪，美国Waters有限公司；MP-420全自动熔点仪，济南海能仪器股份有限公司。

α-蒎烯(GC测定质量分数为98.0%，广西梧州松脂股份有限公司)；系列α-溴代苯乙酮(AR)，硫代氨基脲(AR，广西西纯科技有限公司)；其余所用试剂均为市售分析纯。

1.2 合成路线

新型桃金娘烯醛基噻唑-腙类化合物4a-4p的合成路线如下所示：

4a:R=H; 4b:R=2-F; 4c:R=3-F; 4d:R=4-F; R=3-Cl; 4f:R=4-Cl; 4g:R=4-Br; 4h:R=3, 4-Cl; 4i:R=2, 4-Cl; 4j:R=2, 4-F; 4k:R=p-CH3; 4l:R=p-OCH3; 4m:R=p-CN; 4n:R=p-NO3; 4o:R=m-NO2; 4p:R=p-ph.
1.3 中间产物的合成 1.3.1 桃金娘烯醛(2)的制备

参照林桂汕等(2017)的方法制备桃金娘烯醛(2)，81.0~ 81.5 ℃/ 670 Pa，GC测定含量为90.06%。

1.3.2 桃金娘烯醛基缩氨基硫脲(3)的合成

在250 mL三口烧瓶中加入60 mL水和3.62 g(0.02 mol)氨基硫脲，升温至60 ℃，搅拌至氨基硫脲溶解，再缓慢滴加6.60 g (0.02 mol)桃金娘烯醛(2)的乙醇溶液(60 mL)。滴加完毕后再继续反应1 h，冷却至室温，抽滤，用去离子水：乙醇=1：1的洗提液洗涤滤饼3~4次。烘干后用乙醇进行重结晶，干燥，得到白色晶体，即桃金娘烯醛基缩氨基硫脲(3)，收率91%，纯度98.79%，熔点197~198 ℃。

1.4 目标产物新型桃金娘烯醛基噻唑-腙类化合物(4a-4p)的合成

以4a为例。在50 mL两口烧瓶中加入2.5 mmol桃金娘烯醛基缩氨基硫脲(3)，无水乙醇10 mL，充分搅拌使其溶解。然后将2 mmol α-溴代苯乙酮溶于10 mL乙醇，在磁力搅拌和室温下缓慢滴加至烧瓶中，20 min滴加完毕，采用硅胶波层色谱(TLC)跟踪反应至终点。其后除去溶剂乙醇，残余物用适量乙酸乙酯溶解，分别用15.0 mL氢氧化钠溶液洗涤(3次)和蒸馏水洗涤(1次)，用无水硫酸镁干燥，旋蒸除去乙酸乙酯，得到淡黄色固体粗产物。干燥后，用硅胶柱层析色谱进行纯化[洗脱剂为V(石油醚)：V(乙酸乙酯)=15：1]，得到白色固体4a。化合物4b-4p用同样过程合成而得。

1.5 目标化合物的结构表征

采用KBr压片法测定目标化合物的IR；以CDCl3为溶剂，在600 MHz核磁共振仪上进行1H-NMR和13C-NMR分析；将产物配制成质量浓度为1 mg·L-1的溶液，采用电喷雾电离源(ESI)在液相色谱-质谱联用仪(LC-MS)上进行质谱分析。

1.6 抑菌活性测试

参照Su等(2013)，采用琼脂稀释法，测试目标化合物对水稻纹枯病菌(Rhizoctorzia solani)、黄瓜枯萎病菌(Fusarium oxysporum f. sp. cucumerinum)、花生褐斑病菌(Cercospora arachidicola)、玉米小斑病菌(Helminthosporium maydis)、苹果轮纹病菌(Physalospora piricola)、西瓜炭疽病菌(Colletotrichum lagenarium)、小麦赤霉病菌(Gibberella zeae)和番茄早疫病菌(Altemaria solani) 8种植物病原菌的抑菌活性：将病原菌在含待测化合物质量浓度为50 mg·L-1的药板中置于(24±1)℃的培养箱内培养48 h后，计量各处理菌丝扩展直径，并与不加药剂平板的菌丝扩展直径进行比较，计算相对抑制百分率。活性分级指标：A级：≥90%；B级：70%~90%；C级：50%~70%；D级：≤50%。

2 结果与讨论 2.1 波谱分析 2.1.1 中间体3的表征

中间体3:桃金娘烯醛基缩氨基硫脲，白色固体，收率90%，m.p. 197~198 ℃。1H-NMR (600 MHz, CDCl3) δ: 10.14 (s, 1H, NH), 7.59 (s, 1H, C10—H), 7.06 (s, 1H, NH2), 6.58 (s, 1H, NH2), 6.04 (m, 1H, C3—H), 2.83 (m, 1H, C1—H), 2.49~2.36 (m, 3H, C4—H, C7e—H), 2.15 (m, 1H, C5—H), 1.32 (s, 3H, C9—H), 1.11 (d, J=9.1 Hz, 1H, C7a—H), 0.77 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 177.94(C-11), 145.80(C-10), 144.76(C-6), 135.30(C-3), 40.82(C-5), 40.16(C-1), 37.85(C-7), 32.76(C-6), 31.21(C-4), 26.15(C-9), 21.03(C-8); IR (KBr) ν/cm-1: 3 433, 3 320, 3 197 (N—H), 2 983, 2 930 (C—H), 1 616 (C＝N), 1 363 (C＝S); MS (ESI) m/z: 221.79 ([M-H]+)。

2.1.2 目标产物4的表征

目标化合物4a:黄色粉末，产率51%，m.p. 97.6~98.5 ℃。1H-NMR (600 MHz, CDCl3) δ: 11.28 (s, 1H, NH), 7.79 (d, J=7.4 Hz, 2H, C15—H, C19—H), 7.38 (dd, J=10.6, 4.7 Hz, 2H, C16—H, C18—H), 7.29 (t, J=7.4 Hz, 1H, C17—H), 6.95 (dd, J=9.5, 4.9 Hz, 1H, C10—H), 6.79 (s, 1H, C12—H), 5.19 (s, 1H, C3—H), 2.91 (t, J=5.6 Hz, 1H, C1—H), 2.36 (ddd, J=23.1, 13.0, 2.8 Hz, 3H, C4—H, C7e—H), 2.09 (s, 1H, C5—H), 1.33 (s, 3H, C9—H), 1.07 (d, J=9.0 Hz, 1H, C7a—H), 0.75 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 170.07 (C-11), 151.00 (C-13), 144.93 (C-10), 144.40 (C-2), 134.90 (C-3), 130.06 (C-14), 128.76 (C-17), 127.79 (C-16, C-18), 126.32 (C-15, C-19), 102.88 (C-12), 40.79 (C-5), 39.87 (C-1), 37.64 (C-6), 32.25 (C-7), 31.18 (C-4), 26.14 (C-8), 20.86 (C-9); IR (KBr) ν/cm-1: 3 164 (N—H), 3 066 (C＝C—H), 2 924 (C—H), 1 618 (C＝N), 1 588 (Ar—C＝C), 1 571 (N—H), 1 487 (Ar—C＝C), 1 420 (C—N); MS (ESI) m/z: 323.93 ([M+H]+)。

目标化合物4b:黄色粉末，产率65%，m.p. 78.7~79.2 ℃。1H-NMR (600 MHz, CDCl3) δ: 10.58 (s, 1H, NH), 7.98 (dd, J=7.8, 6.2 Hz, 1H, C19—H), 7.26~7.22 (m, 1H, C17—H), 7.16~7.12 (m, 2H, C16—H, C18—H), 7.10 (d, J=2.2 Hz, 1H, C10—H), 7.09 (s, 1H, C12—H), 5.42 (s, 1H, C3—H), 2.94 (td, J=5.8, 1.0 Hz, 1H, C1—H), 2.47~2.31 (m, 3H, C4—H, C7e—H), 2.12 (d, J=1.1 Hz, 1H, C5—H), 1.35 (s, 3H, C9—H), 1.10 (d, J=9.0 Hz, 1H, C7a—H), 0.76 (d, J=5.8 Hz, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 168.76 (C-11), 161.06 (C-13), 159.40 (C-15), 144.99 (C-10), 144.13 (C-2), 130.26 (C-3), 129.58 (C-17), 128.76 (C-19), 124.47 (C-18), 122.49 (C-14), 116.00 (C-16), 108.20 (C-12), 40.79 (C-5), 39.96 (C-1), 37.66 (C-6), 32.29 (C-7), 31.19 (C-4), 26.12 (C-8), 20.88 (C-9); IR (KBr) ν/cm-1: 3 178 (N—H), 3 075 (C＝C—H), 2 923 (C—H), 1 618 (C＝N), 1 579 (Ar—C＝C), 1 487 (Ar—C＝C), 1 436 (C—N), 1 222, 1 123, 1 053, 764, 747; MS (ESI) m/z: 341.86 ([M+H]+)。

目标化合物4c:黄色粉末，产率56%，m.p. 82.6~83.8 ℃。1H-NMR (600 MHz, CDCl3) δ: 11.39~10.31 (m, 1H, NH), 7.57 (d, J=7.9 Hz, 1H, C18—H), 7.50~7.46 (m, 1H, C19—H), 7.33 (td, J=8.0, 6.0 Hz, 1H, C15—H), 7.04 (s, 1H, C17—H), 7.01~6.97 (m, 1H, C10—H), 6.83 (s, 1H, C12—H), 5.35 (s, 1H, C3—H), 2.94~2.90 (m, 1H, C1—H), 2.46~2.28 (m, 3H, C4—H, C7e—H), 2.11 (d, J=1.0 Hz, 1H, C5—H), 1.34 (s, 3H, C9—H), 1.10 (d, J=9.0 Hz, 1H, C7a—H), 0.76 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 169.87 (C-11), 163.96 (C-16), 149.63 (C-12), 145.00 (C-2), 144.49 (C-10), 136.96 (C-3), 130.48 (C-17), 130.28 (C-18), 121.83 (C-14), 114.63 (C-15), 113.17 (C-19), 104.05 (C-13), 40.78 (C-5), 39.94 (C-1), 37.64 (C-6), 32.31 (C-7), 31.18 (C-4), 26.12 (C-8), 20.84 (C-9);IR (KBr) ν/cm-1: 3 176 (N—H), 3 069 (C＝C—H), 2 914 (C—H), 1 616 (C＝N), 1 584 (Ar—C＝C), 1 469 (Ar—C＝C), 1 439 (C—N), 1 154, 1 124, 1 052, 949, 784, 722; MS (ESI) m/z: 341.89 ([M+H]+)。

目标化合物4d:黄色粉末，产率68%，m.p. 143.1~144.1 ℃。1H-NMR (600 MHz, CDCl3) δ: 11.21 (s, 1H, NH), 7.77~7.73 (m, 2H, C15—H, C19—H), 7.09~7.04 (m, 2H, C16—H, C18—H), 6.96 (s, 1H, C10—H), 6.72 (s, 1H, C12—H), 5.30 (s, 1H, C3—H), 2.91 (dd, J=8.1, 3.1 Hz, 1H, C1—H), 2.46~2.28 (m, 3H, C4—H, C7e—H), 2.11 (d, J=0.9 Hz, 1H, C5—H), 1.34 (s, 3H, C9—H), 1.09 (d, J=9.0 Hz, 1H, C7a—H), 0.76 (d, J=4.7 Hz, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 170.06 (C-11), 163.38 (C-13), 161.74 (C-10), 149.99 (C-2), 144.93 (C-3), 144.42 (C-14), 131.21 (C-17), 130.32 (C-18), 127.97 (C-16), 115.70 (C-15), 115.56 (C-19), 102.56 (C-12), 40.78 (C-5), 39.90 (C-1), 37.63 (C-6), 32.29 (C-7), 31.17 (C-4), 26.12 (C-8), 20.84 (C-9);IR (KBr) ν/cm-1: 3 180 (N—H), 3 073 (C＝C—H), 2 909 (C—H), 1 618 (C＝N), 1 588 (Ar—C＝C), 1 491 (Ar—C＝C), 1 439 (C—N), 1 238, 1 222, 1 127, 1 053, 840, 733; MS (ESI) m/z: 341.86 ([M+H]+)。

目标化合物4e:黄色粉末，产率72%，m.p. 153.1~153.5 ℃。1H-NMR (600 MHz, CDCl3) δ: 11.39~10.31 (m, 1H, NH), 7.57 (d, J=7.9 Hz, 1H, C18—H), 7.50~7.46 (m, 1H, C19—H), 7.33 (td, J=8.0, 6.0 Hz, 1H, C15—H), 7.04 (s, 1H, C17—H), 7.01~6.97 (m, 1H, C10—H), 6.83 (s, 1H, C12—H), 5.35 (s, 1H, C3—H), 2.94~2.90 (m, 1H, C1—H), 2.46~2.28 (m, 3H, C4—H, C7e—H), 2.11 (d, J=1.0 Hz, 1H, C5—H), 1.34 (s, 3H, C9—H), 1.10 (d, J=9.0 Hz, 1H, C7a—H), 0.76 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 169.98 (C-11), 149.54 (C-12), 144.98 (C-10), 144.40 (C-2), 136.61 (C-16), 134.72 (C-14), 130.49 (C-3), 130.02 (C-18), 127.72 (C-17), 126.32 (C-15), 124.34 (C-19), 104.12 (C-13), 40.79 (C-5), 39.95 (C-1), 37.64 (C-6), 32.32 (C-7), 31.21 (C-4), 26.13 (C-8), 20.89 (C-9);IR (KBr) ν/cm-1: 3 190 (N—H), 3 071 (C＝C—H), 2 926 (C—H), 1 619 (C＝N), 1 584 (Ar—C＝C), 1 553 (N—H), 1 457 (Ar—C＝C), 1 440 (C—N), 1 387, 1 077, 828; MS (ESI) m/z: 357.84 ([M+H]+)。

目标化合物4f:黄色粉末，产率75%，m.p. 162.8~163.5 ℃。1H-NMR (600 MHz, CDCl3) δ: 11.47~11.03 (s, 1H, NH), 7.71~7.69 (d, J=8.5 Hz, 2H, C16—H, C18—H), 7.35~7.32 (d, J=8.5 Hz, 2H, C15—H, C19—H), 6.93 (s, 1H, C10—H), 6.77 (s, 1H, C13—H), 5.25 (s, 1H, C3—H), 2.91 (t, J=5.2 Hz, 1H, C1—H), 2.46~2.30 (ddt, J=37.4, 19.3, 11.1 Hz, 3H, C4—H, C7e—H), 2.12 (m, 1H, C5—H), 1.35 (s, 3H, C9—H), 1.10 (dd, J=9.0, 1.9 Hz, 1H, C7a—H), 0.78 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 170.17 (C-11), 149.89 (C-12), 144.79 (C-10), 144.64 (C-2), 133.64 (C-17), 133.44 (C-3), 130.57 (C-14), 128.91 (C-15，C-19), 127.66 (C-16，C-18), 103.32 (C-13), 40.79 (C-1), 39.86 (C-6), 37.66 (C-5), 32.36 (C-7), 31.17 (C-4), 26.14 (C-9), 20.86 (C-9); IR (KBr) ν/cm-1: 3 200 (N—H), 3 065 (C＝C—H), 2 918 (C—H), 1 614 (C＝N), 1 588 (Ar— C＝C), 1 567 (N—H), 1 479 (Ar—C＝C), 1 439 (C—N), 1 092, 1 050, 827; MS (ESI) m/z: 357.81 ([M+H]+)。

目标化合物4g:黄色粉末，产率70%，m.p. 142.3~143.1 ℃。1H-NMR (600 MHz, CDCl3) δ: 11.24 (s, 1H, NH), 7.65~7.61 (d, J=8.5 Hz, 2H, C16—H, C18—H), 7.51~7.47 (d, J=8.5 Hz, 2H, C15—H, C19—H), 6.92 (s, 1H, C10—H), 6.78 (s, 1H, C12—H), 5.24 (s, 1H, C3—H), 2.91 (t, J=5.2 Hz, 1H, C1—H), 2.40 (ddt, J=37.4, 19.3, 11.1 Hz, 3H, C4—H, C7e—H), 2.12 (m, 1H, C5—H), 1.35 (s, 3H, C9—H), 1.11 (dd, J=9.0, 1.9 Hz, 1H, C7a—H), 0.78 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 170.24 (C-11), 149.91 (C-12), 144.73 (C-10), 133.87 (C-2), 131.86 (C-17), 130.66 (C-3), 127.99 (C-16，C-18), 121.82 (C-15，C-19), 103.41 (C-13), 40.80 (C-1), 39.85 (C-6), 37.68 (C-5), 32.40 (C-7), 31.17 (C-4), 26.14 (C-8), 20.91 (C-9); IR (KBr) ν/cm-1: 3 167 (N—H), 3 065 (C＝C—H), 2 922 (C—H), 1 618 (C＝N), 1 586 (Ar—C＝C), 1 561 (N—H), 1 475 (Ar—C＝C), 1 434 (C—N), 1 114, 1 052, 101, 826, 726; MS (ESI) m/z: 401.75 ([M+H]+)。

目标化合物4h:黄色粉末，产率49%，m.p. 144.5~145.4 ℃。1H-NMR (600 MHz, CDCl3) δ: 10.89~10.51 (s, 1H, NH), 7.87~7.84 (s, 1H, C15—H), 7.60~7.57 (m, 1H, C19—H), 7.44 (m, 1H, C18—H), 7.06~7.04 (s, 1H, C10—H), 6.84~6.81 (s, 1H, C12—H), 5.41~5.38 (s, 1H, C3—H), 2.94 (t, J=5.2 Hz, 1H, C1—H), 2.48~2.32 (ddt, J=37.4, 19.3, 11.1 Hz, 3H, C4—H, C7e—H), 2.13 (m, 1H, C5—H), 1.35 (s, 3H, C9—H), 1.13 (dd, J=9.0, 1.9 Hz, 1H, C7a—H), 0.78 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 169.90 (C-11), 148.69 (C-12), 144.91 (C-10), 144.47 (C-2), 134.89 (C-16), 132.87 (C-17), 131.59 (C-3), 130.83 (C-18), 130.65 (C-14), 128.09 (C-15), 125.43 (C-19), 104.45 (C-13), 40.79 (C-1), 39.97 (C-6), 37.64 (C-5), 32.39 (C-7), 31.21 (C-4), 26.12 (C-8), 20.90 (C-9); IR (KBr) ν/cm-1: 3 174 (N—H), 3 075 (C＝C—H), 2 923 (C—H), 1 618 (C＝N), 1 579 (Ar—C＝C), 1 458 (Ar—C＝C), 1 438 (C—N), 1 386, 1 308, 1 135, 1 117, 1 053, 827, 722.6; MS (ESI) m/z: 391.77 ([M+H]+)。

目标化合物4i:黄色粉末，产率52%，m.p. 162.8~163.5 ℃。1H-NMR (600 MHz, CDCl3) δ:11.52~11.04 (s, 1H, NH), 7.72 (d, J=8.4 Hz, 1H, C19—H), 7.48 (d, J=2.1 Hz, 1H, C16—H), 7.23 (dd, J=8.4, 2.1 Hz, 1H, C18—H), 7.04 (d, J=2.3 Hz, 1H, C10—H), 6.81 (s, 1H, C12—H), 5.30 (s, 1H, C3—H), 2.91 (t, J=5.6 Hz, 1H, C1—H), 2.47~2.32 (ddd, J=23.1, 13.0, 2.8 Hz, 3H, C4—H, C7e—H), 2.12 (s, 1H, C5—H), 1.35 (s, 3H, C9—H), 1.10 (d, J=9.0 Hz, 1H, C7a—H), 0.78 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 169.26 (C-11), 145.94 (C-12), 144.91 (C-10), 144.20 (C-2), 133.92 (C-17), 132.73 (C-15), 132.20 (C-3), 131.98 (C-16), 130.48 (C-19), 130.15 (C-14), 127.41 (C-18), 108.51 (C-13), 40.81 (C-1), 39.88 (C-6), 37.65 (C-5), 32.41 (C-7), 31.17 (C-4), 26.15 (C-8), 20.86 (C-9); IR (KBr) ν/cm-1: 3 176 (N—H), 3 067 (C＝C—H), 2 914 (C—H), 1 618 (C＝N), 1 602 (Ar—C＝C), 1 571 (N—H), 1 467 (Ar—C＝C), 1 430 (C—N), 1 125, 1 048, 792, 751, 722; MS (ESI) m/z: 391.75 ([M+H]+)。

目标化合物4j:黄色粉末，产率68%，m.p. 135.1~135.8 ℃。1H-NMR (600 MHz, CDCl3) δ: 10.57 (s, 1H, NH), 7.94 (dt, J=15.3, 7.6 Hz, 1H, C19—H), 7.09 (d, J=11.9 Hz, 1H, C18—H), 7.02 (d, J=2.1 Hz, 1H, C16—H), 6.90 (dt, J=4.3, 2.6 Hz, 1H, C10—H), 6.89~6.86 (m, 1H, C12—H), 5.46 (s, 1H, C3—H), 2.94 (t, J=5.5 Hz, 1H, C1—H), 2.50~2.30 (m, 3H, C4—H, C7e—H), 2.13 (s, 1H, C5—H), 1.35 (s, 3H, C9—H), 1.11 (d, J=9.0 Hz, 1H, C7a—H), 0.78 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 168.85 (C-11), 162.78 (C-15), 161.09 (C-17), 159.42 (C-12), 145.00 (C-10), 144.21 (C-2), 143.47 (C-3), 130.47 (C-16), 119.04 (C-19), 111.55 (C-14), 107.56 (C-18), 104.28 (C-13), 40.79 (C-1), 39.99 (C-6), 37.65 (C-5), 32.32 (C-7), 31.19 (C-4), 26.12 (C-8), 20.86 (C-9); IR (KBr) ν/cm-1: 3 184 (N—H), 3 077 (C＝C—H), 2 917 (C—H), 1 620 (C＝N), 1 588 (Ar—C＝C), 1 567 (N—H), 1 489 (Ar—C＝C), 1 443 (C—N), 1 425, 1 047, 969, 835; MS (ESI) m/z: 359.83 ([M+H]+)。

目标化合物4k:黄色粉末，产率71%，m.p. 149.8~150.4 ℃。1H-NMR (600 MHz, CDCl3) δ: 11.38 (s, 1H, NH), 7.69 (d, J=8.1 Hz, 2H, C15—H, C19—H), 7.21 (d, J=8.0 Hz, 2H, C16—H, C18—H), 6.92 (s, 1H, C10—H), 6.74 (s, 1H, C12—H), 5.19 (s, 1H, C3—H), 2.93 (t, J=5.3 Hz, 1H, C1—H), 2.49~2.25 (m, 3H, C4—H, C7e—H), 2.38 (s, 3H, C20—H), 2.12 (m, 1H, C5—H), 1.36 (s, 3H, C9—H), 1.10 (d, J=9.0 Hz, 1H, C7a—H), 0.78 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 170.00 (C-11), 151.12 (C-12), 144.96 (C-10), 144.42 (C-2), 137.62 (C-17), 132.27 (C-3), 129.85 (C-14), 129.42 (C-16，C-18), 126.37 (C-15，C-19), 102.02 (C-13), 40.80 (C-1), 39.82 (C-6), 37.63 (C-5), 32.34 (C-7), 31.20 (C-4), 26.13 (C-20), 21.19 (C-8), 20.80 (C-9); IR (KBr) ν/cm-1: 3 178 (N—H), 3 071 (C＝C—H), 2 917 (C—H), 1 616 (C＝N), 1 587 (Ar—C＝C), 1 495 (Ar—C＝C), 1 440 (C—N), 1 355, 1 323, 1 123, 1 051, 819, 726; MS (ESI) m/z: 337.87 ([M+H]+)。

目标化合物4l:黄色粉末，产率51%，m.p. 150.4~151.0 ℃。1H-NMR (600 MHz, CDCl3) δ: 11.38 (s, 1H, NH), δ 7.72~7.69 (m, 2H, C15—H, C19—H), 6.96 (d, J=4.4 Hz, 1H, C10—H), 6.92~6.89 (m, 2H, C16—H, C18—H), 6.63 (d, J=0.7 Hz, 1H, C12—H), 5.25 (s, 1H, C3—H), 3.81 (s, 3H, C20—H), 2.91 (t, J=5.5 Hz, 1H, C1—H), 2.45~2.25 (m, 3H, C4—H, C7e—H), 2.10 (m, 1H, C5—H), 1.34 (s, 3H, C9—H), 1.08 (d, J=9.0 Hz, 1H, C7a—H), 0.75 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3)δ: 170.02 (C-11), 159.52 (C-12), 150.31 (C-10), 145.23~145.09 (C-2), 144.84 (C-17), 133.34 (C-3), 130.19 (C-14), 127.64 (C-15，C-19), 114.14 (C-16，C-18), 100.98 (C-13), 55.29 (C-20), 40.79 (C-1), 39.84 (C-6), 37.62 (C-5), 32.29 (C-7), 31.21 (C-4), 26.13 (C-8), 20.86 (C-9); IR (KBr) ν/cm-1: 3 173 (N—H), 3 071 (C＝C—H), 2 932 (C—H), 1 616 (C＝N), 1 583 (Ar—C＝C), 1 492 (Ar—C＝C), 1 442 (C—N), 1 255, 1 175, 1 123, 1 030, 837; MS (ESI) m/z: 353.89 ([M+H]+)。

目标化合物4m:黄色粉末，产率69%，m.p. 174.1~174.5 ℃。1H-NMR (600 MHz, CDCl3) δ: 10.52 (s, 1H, NH), 7.87 (d, J=8.4 Hz, 2H, C15—H, C19—H), 7.66 (d, J=8.4 Hz, 2H, C16—H, C18—H), 7.13~7.05 (m, 1H, C10—H), 6.98 (s, 1H, C12—H), 5.43 (d, J=27.2 Hz, 1H, C3—H), 2.93 (t, J=5.1 Hz, 1H, C1—H), 2.50~2.30 (m, 3H, C4—H, C7e—H), 2.14 (s, 1H, C5—H), 1.36 (s, 3H, C9—H), 1.10 (dd, J=25.4, 9.1 Hz, 1H, C7a—H), 0.77 (d, J=30.0 Hz, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 169.94 (C-11), 149.11 (C-12), 144.91 (C-10), 144.63 (C-2), 138.87 (C-3), 132.60 (C-14), 131.04 (C-15，C-19), 126.57 (C-16，C-18), 118.87 (C-17), 110.92 (C-20), 106.32 (C-13), 40.76 (C-1), 39.98 (C-6), 37.66 (C-5), 32.37 (C-7), 31.18 (C-4), 26.10 (C-8), 20.90 (C-9); IR (KBr) ν/cm-1: 3 174 (N—H), 3 104 (C＝C—H), 2 916 (C—H), 1 618 (C＝N), 1 606 (Ar—C＝C), 1 557 (N—H), 1 522 (Ar—C＝C), 1 420 (C—N), 1 347, 1 271, 1 114, 1 053, 839; MS (ESI) m/z: 348.85 ([M+H]+)。

目标化合物4n:黄色粉末，产率75%，m.p. 171.6~172.4 ℃。1H-NMR (600 MHz, CDCl3) δ: 9.70 (s, 1H, NH), 8.24 (d, J=8.8 Hz, 2H, C15—H, C19—H), 7.93 (d, J=8.8 Hz, 2H, C16—H, C18—H), 7.26 (s, 1H, C12—H), 7.06 (s, 1H, C10—H), 5.64 (s, 1H, C3—H), 2.95 (t, J=5.5 Hz, 1H, C1—H), 2.50~2.32 (m, 3H, C4—H, C7e—H), 2.15 (s, 1H, C5—H), 1.37 (s, 3H, C9—H), 1.14 (d, J=9.1 Hz, 1H, C7a—H), 0.79 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 169.89 (C-11), 148.85 (C-12), 146.94 (C-10), 144.90 (C-2), 144.66 (C-17), 140.70 (C-14), 131.13 (C-3), 126.60 (C-15，C-19), 124.19 (C-16，C-18), 107.16 (C-13), 40.73 (C-1), 40.00 (C-6)), 37.63 (C-5), 32.35 (C-7), 31.17 (C-4), 26.09 (C-8), 20.85 (C-9); IR (KBr) ν/cm-1: 3 125 (N—H), 3 067 (C＝C—H), 2 926 (C—H), 1 616 (C＝N), 1 602 (Ar—C＝C), 1 565 (N—H), 1 508 (Ar—C＝C), 1 426 (C—N), 1 341, 1 284, 1 112, 1 051, 862, 847, 716; MS (ESI) m/z: 368.85 ([M-H]+)。

目标化合物4o:黄色粉末，产率70%，m.p. 119.4~120.3 ℃。1H-NMR (600 MHz, CDCl3) δ: 9.86-9.65 (s, 1H, NH), 8.65 (s, 1H, C15—H), 8.12~8.14 (m, J=7.4 Hz, 1H, C17—H), 8.09~8.12 (m, J=7.9 Hz, 1H, C19—H), 7.55 (d, J=7.4 Hz, 1H, C18—H), 7.26~7.24 (dd, J=9.5, 4.9 Hz, 1H, C10—H), 7.02 (s, 1H, C12—H), 5.63~5.61 (s, 1H, C3—H), 2.97 (t, J=5.6 Hz, 1H, C1—H), 2.40 (ddd, J=23.1, 13.0, 2.8 Hz, 3H, C4—H, C7e—H), 2.16~2.13 (s, 1H, C5—H), 1.37~1.36 (s, 3H, C9—H), 1.14 (d, J=9.0 Hz, 1H, C7a—H), 0.80~0.78 (s, 3H, C8—H); 13C NMR (151 MHz, CDCl3) δ: 169.32 (C-11), 148.70 (C-16), 148.64 (C-12), 145.00 (C-10), 144.18 (C-2), 136.48 (C-3), 131.71 (C-14), 130.98 (C-19), 129.61 (C-18), 122.19 (C-15), 120.88 (C-17), 105.59 (C-13), 40.77 (C-1), 40.09 (C-6), 37.67 (C-5), 32.36 (C-7), 31.20 (C-4), 26.10 (C-8), 20.88 (C-9); IR (KBr) ν/cm-1: 3167 (N—H), 3 085 (C＝C—H), 2 918 (C—H), 1 614 (C＝N), 1 569 (Ar—C＝C), 1 542 (N—H), 1 513 (Ar—C＝C), 1 446(C—N), 1 350, 1 328, 1 124, 1059, 738, 716; MS (ESI) m/z: 368.85 ([M+H]+)。

目标化合物4p:黄色粉末，产率44%，m.p. 185.6~186.4 ℃。1H-NMR (600 MHz, CDCl3) δ: 11.42 (s, 1H, NH), 7.87 (d, J=8.2 Hz, 2H, C15—H, C19—H), 7.63 (d, J=8.3 Hz, 2H, C16—H, C18—H), 7.60 (d, J=7.3 Hz, 2H, C21—H, C25—H), 7.44 (t, J=7.7 Hz, 2H, C24—H, C22—H), 7.35 (t, J=7.4 Hz, 1H, C23—H), 6.97 (d, J=10.0 Hz, 1H, C10—H), 6.84 (d, J=15.9 Hz, 1H, C12—H), 5.16 (s, 1H, C3—H), 2.91 (t, J=5.4 Hz, 1H, C1—H), 2.42~2.10 (m, 3H, C4—H, C7e—H), 2.04 (s, 1H, C5—H), 1.31 (s, 3H, C9—H), 1.04 (d, J=9.0 Hz, 1H, C7a—H), 0.68 (s, 3H, C8—H); 13C-NMR (151 MHz, CDCl3) δ: 170.19 (C-11), 150.73 (C-12), 144.87 (C-10), 144.50 (C-2), 140.62 (C-3), 140.61 (C-14), 133.93 (C-17), 130.19 (C-20), 128.76 (C-22, C-24), 127.44 (C-16, C-18), 127.35 (C-23), 126.96 (C-15, C-19), 126.86 (C-21, C-25), 102.96 (C-13), 40.75 (C-1), 39.81 (C-6), 37.61 (C-5), 32.22 (C-7), 31.16 (C-4), 26.11 (C-8), 20.78 (C-9); IR (KBr) ν/cm-1: 3 180 (N—H), 3 090 (C＝C—H), 2 952 (C—H), 1 622 (C＝N), 1 596 (Ar—C＝C), 1 561 (N—H), 1 524 (Ar—C＝C), 1 434 (C—N), 1 114, 1 052, 101, 826, 726; MS (ESI) m/z: 399.86 ([M+H]+)。

在化合物4的IR谱图中，3 150~3 200 cm-1处的吸收峰为N—H的伸缩振动吸收峰，1 610~1 620 cm-1处的吸收峰为C＝N的伸缩振动吸收峰，1 580~1 530 cm-1处的吸收峰为N—H的面内弯曲振动吸收峰。在化合物4的1H-NMR谱图中，化学位移在11.82~13.54处为上N—H的吸收峰，从化合物4的13C-NMR谱图看，出现了C＝N的吸收峰，化学位移在164~175之间。从质谱数据中可看出化合物4a-4p的质荷比与所设计的目标化合物相吻合。

2.2 抑菌活性测试结果

目标产物4对8种测试病原菌的抑菌率见表 1。在50 mg·L-1下，目标化合物4对8种供试植物病原菌均有不同程度的抑制作用。结果显示，目标化合物4对8种植物病原菌的抑菌活性好于骨架化合物桃金娘烯醛。总体上，目标化合物对苹果轮纹病菌的抑制效果最好，平均抑菌率为64.2%，有12个目标化合物的抑菌率达60%以上，其中化合物4n (R=4-NO2)的抑菌率高达90.6%(活性级别为A级)，化合物4f (R=4-Cl)、化合物4k (R=4-CH3)和化合物4m (R=4-CN)的抑菌率分别为74.6%、71.1%和79.4%(活性级别为B级)。总体上，取代基的引入使目标化合物对8种植物病原菌的抑菌活性均有所提高，其中对位引入硝基(化合物4n)时活性最大，平均抑菌率达55.6%。还有，除卤素外，在4位引入吸电子基团(如4-NO2、4-CN)比引入给电子基团(如4-CH3、4-OCH3)时的生物活性要好。

表 1 化合物4的抑菌活性 Tab.1 The antifungal activities of compound 4
3 结论

将α-蒎烯经烯丙位甲基氧化得到桃金娘烯醛，再通过对其醛基的化学改性，合成得到16个新型桃金娘烯醛基噻唑-腙类化合物4a-4p。利用FT-IR、1H-NMR、13C-NMR和ESI-MS等多种手段确认了目标化合物的结构。目标产物的抑菌活性测试结果表明：在50 mg·L-1质量浓度下，合成得到的16个桃金娘烯醛基噻唑-腙类化合物4a-4p对所测的8种植物病原菌均显示出一定的抑制活性，且对苹果轮纹病菌的抑制效果最好，抑菌率在60%的化合物有12个，化合物4n(R=4-NO2)的抑菌率高达90.6%(活性级别为A级)，是值得进一步研究的先导化合物。

参考文献(References)
白雪, 段文贵, 林桂汕, 等. 2015. 新型桃金娘烯醛基双酰胺-噻二唑化合物的合成及其抗真菌活性[J]. 合成化学, 23(11): 1000-1004, 1012.
(Bai X, Duan W G, Lin G S, et al. 2015. Synthesis and antifungal activities of novel myrtenal-based bisamide-thiadiazole compounds[J]. Chinese Journal of Synthetic Chemistry, 23(11): 1000-1004, 1012. [in Chinese])
陈才俊, 宋宝安. 2005. 噻唑类杀虫剂的研究进展[J]. 农药, 44(2): 53-55, 65.
(Chen C J, Song B A. 2005. Research advances with thiazole insecticides[J]. Chinese Journal of Pesticides, 44(2): 53-55, 65. [in Chinese])
陈乃源, 段文贵, 林桂汕, 等. 2016. 去氢枞酸基B环并噻唑-酰胺化合物的合成及抑菌活性[J]. 精细化工, 33(7): 811-819.
(Chen N Y, Duan W G, Lin G S, et al. 2016. Synthesis and antifungal activity of dehydroabietic acid-based B ring-fused-thiazole-amide compounds[J]. Fine Chemicals, 33(7): 811-819. [in Chinese])
黄铎云, 段文贵, 林桂汕, 等. 2016. 2-取代酰氨基-5-(α-龙脑烯醛基)-1, 3, 4-噻二唑化合物的合成及抑菌活性[J]. 林产化学与工业, 36(1): 61-69.
(Huang D Y, Duan W G, Lin G S, et al. 2016. Synthesis and antifungal activities of 2-sustituted acylamino-5-α-campholenic aldehyde-based-1, 3, 4-thiadiazole compounds[J]. Chemistry and Industry of Forest Products, 36(1): 61-69. [in Chinese])
康圣鸿, 胡德禹, 吴剑, 等. 2012. 含腙类结构化合物生物活性研究进展[J]. 农药, 51(4): 238-242, 245.
(Kang S H, Hu D Y, Wu J, et al. 2012. Research progress for biological activity of compounds containing hydrazone group[J]. Agrochemicals, 51(4): 238-242, 245. [in Chinese])
李英俊, 李春燕, 靳焜, 等. 2012. 新型含噁二唑环的苯并噁/噻唑啉酮衍生物的合成、表征及生物活性[J]. 化学学报, 70(2): 151-160.
(Li Y J, Li C Y, Jin K, et al. 2012. Synthesis and biological activities of novel benzoxazolinone/benzothiazolone derivatives containing oxadiazole moiety[J]. Acta Chimica Sinica, 70(2): 151-160. [in Chinese])
林桂汕, 段文贵, 利镇升, 等. 2017. 桃金娘烯醛基噻二唑-酰胺化合物的合成及性能[J]. 精细化工, 34(5): 588-595.
(Lin G S, Duan W G, Li Z S, et al. 2017. Synthesis and properties of myrtenal-based thiadiazole-amide compounds[J]. Fine Chemicals, 34(5): 588-595. [in Chinese])
马献力, 闵方倩, 段文贵, 等. 2015. 樟脑酸基苯磺酰胺类化合物的合成及抑菌活性研究[J]. 林产化学与工业, 35(1): 30-38.
(Ma X L, Min F Q, Duan W G, et al. 2015. Synthesis and fungicidal activity of camphoric acid-based benzenesulfonamide compounds[J]. Chemistry and Industry of Forest Products, 35(1): 30-38. [in Chinese])
彭莉, 殷彩霞, 张凤梅, 等. 2013. 桃金娘烯醛合成及其生物活性测试[J]. 化学与生物工程, 30(2): 50-52, 66.
(Peng L, Yin C X, Zhang F M, et al. 2013. Synthesis and bioactivity determination of myrtenal[J]. Chemistry & Bioengineering, 30(2): 50-52, 66. [in Chinese])
汪飞, 曹瑾, 袁莉萍, 等. 2006. 新型腙类衍生物的合成及其生物活性[J]. 农药学学报, 8(2): 176-179.
(Wang F, Cao J, Yuan L P, et al. 2006. Synthesis and bioactivity of a series of novel hydra zone derivatives[J]. Chinese Journal of Pesticide Science, 8(2): 176-179. [in Chinese])
吴光燧, 段文贵, 林桂汕, 等. 2014. N-(4-取代氨基磺酰基)苯基-酮基蒎酸酰胺的合成及生物活性[J]. 农药学学报, 16(1): 8-13.
(Wu G S, Duan W G, Lin G S, et al. 2014. Synthesis and biological activity of N-(4-substituted amino-sulfonyl)-phenyl-ketopinamides[J]. Chinese Journal of Pesticide Science, 16(1): 8-13. [in Chinese])
Duan W G, Li X R, Mo Q J, et al. 2011. Synthesis and herbicidal activity of 5-dehydroabietyl-1, 3, 4-oxadiazole derivatives[J]. Holzforschung, 65(2): 191-197.
Galayko N V, Tolmacheva 1 A, Grishko V V, et al. 2010. Antiviral activity of 2, 3-secotriterpenic hydrazones of lupine and 19beta, 28-epoxy-18alpha-oleanane type[J]. Bioorganicheskaia Khimiia, 36(4): 516-521.
Hardie J, Isaacs R, Pickett J A, et al. 1994. Methyl salicylate and (-)-(1R, 5S)-myrtenal are plant-derived repellents for black bean Aphid, Aphis fabae SCOP[J]. (Homoptera:Aphididae). Journal of Chemical Ecology, 20(11): 2847-2855. DOI:10.1007/BF02098393
Hari-Babu L, Perumal S, Balasubramanian M P. 2012. Myrtenal, a natural monoterpene, down-regulates TNF-α expression and suppresses carcinogen-induced hepatocellular carcinoma in rats[J]. Molecular and Cellular Biochemistry, 369(1/2): 183-193.
Helal M H M, Salem M A, El-Gaby M S A, et al. 2013. Synthesis and biological evaluation of some novel thiazole compounds as potential anti-inflammatory agents[J]. European Journal of Medicinal Chemistry, 65: 517-526. DOI:10.1016/j.ejmech.2013.04.005
Kalkhambkar R G, Kulkarni G M, Shivkumar H, et al. 2007. Synthesis of novel triheterocyclic thiazoles as anti-inflammatory and analgesic agents[J]. European Journal of Medicinal Chemistry, 42(10): 1272-1276. DOI:10.1016/j.ejmech.2007.01.023
Kamchonwongpaisan S, Nilanonta C, Tamchompoo B, et al. 1995. An antimalarial peroxide from amomum krervanh pierre[J]. Tetrahedron Letters, 36(11): 1821-1824. DOI:10.1016/0040-4039(95)00152-3
Kaplancikli Z A, Altintop M D, Ozdemir A, et al. 2012. Synthesis and biological evaluation of some hydrazone derivatives as anti-inflammatory agents[J]. Letters in Drug Design & Discovery, 9(3): 310-315.
Lin G S, Ma C H, Duan W G, et al. 2014. Synthesis and biological activities of α-pinene-based dithiadiazoles[J]. Holzforschung, 68(1): 75-82.
Lingaiah H B, Natarajan N, Thamaraiselvan R, et al. 2013. Myrtenal ameliorates diethylnitrosamine-induced hepatocarcinogenesis through the activation of tumor suppressor protein p53 and regulation of lysosomal and mitochondrial enzymes[J]. Fundamental & Clinical Pharmacology, 27(4): 443-454.
Osorio T M, Monache F D, Chiaradia L D, et al. 2012. Antibacterial activity of chalcones, hydrazones and oxadiazoles against methicillin-resistant Staphylococcus aureus[J]. Bioorganic & Medicinal Chemistry Letters, 22(1): 225-230.
Rai N P, Venu T D, Manuprasad B K, et al. 2010. Synthesis of some novel 2-[2-(aroyl-aroxy)-methyl]-4-phenyl-1, 3-thiazoles as potent anti-inflammatory agents[J]. Chemical Biology & Drug Design, 75(4): 400-406.
Su N N, Li Y, Yu S J, et al. 2013. Microwave-assisted synthesis of some novel 1, 2, 3-triazoles by click chemistry and their biological activity[J]. Research on Chemical Intermediates, 39(2): 759-766. DOI:10.1007/s11164-012-0595-9
Terzioglu N, Gürsoy A. 2003. Synthesis and anticancer evaluation of some new hydrazone derivatives of 2, 6-dimethylimidazo[2, 1-b] [1, 3, 4]thiadiazole-5-carbohydrazide[J]. European Journal of Medicinal Chemistry, 38(7/8): 781-786.
Vegezzi D. 1980. Method for the preparation of verbenone, myrtenal and pinocarveol and their therapeutical use[J]. United States Patent: 4190675.
Wu J, Song B A, Hu D Y, et al. 2012. Design, synthesis and insecticidal activities of novel pyrazole amides containing hydrazone substructures[J]. Pest Management Science, 68(5): 801-810. DOI:10.1002/ps.v68.5
Zaharia V, Ignat A, Palibroda N, et al. 2010. Synthesis of some p-toluenesulfonyl-hydrazinothiazoles and hydrazino-bis-thiazoles and their anticancer activity[J]. European Journal of Medicinal Chemistry, 45(11): 5080-5085. DOI:10.1016/j.ejmech.2010.08.017