源自内生真菌的倍半萜类新颖高效抑菌化合物的衍生合成与生物活性研究
|
摘要
近年来,基于天然产物的新颖杀菌剂创制研究层出不穷,像源自于微生物的代谢产物井冈霉素,作为农用杀菌剂多年来对水稻纹枯病的防治效果一直很好。Stroblurins类杀菌剂也是以天然产物为母体经过结构修饰,创制出的一系列高效、广谱、.安全的杀菌剂,成为当今杀菌剂市场最活跃、最有发展潜力的一类新品种。
木霉菌是植物内生真菌系列中很重要的一类生防菌,木霉菌的广泛应用与其主要代谢产物木霉菌素广谱高效的抑菌活性是分不开的。为了更细致的研究木霉属系列代谢产物,更好的发挥木霉菌的用途,也为了寻求更优异的结构骨架或新颖先导结构,本文以南方红豆杉Taxus chinesis var. mairei内生真菌紫杉木霉Trichoderma taxi sp. nov.菌的代谢产物木霉菌素为先导化合物,根据活性亚结构连接、生物等排性原理等方法,对此类倍半萜结构进行详细的结构修饰,细致的生物活性筛选,具体研究内容及结果如下：
1、系统总结了内生真菌中单端胞霉烯类化合物的研究现状,木霉菌生物防治应用、木霉菌素的发酵、结构、活性,以及细菌、真菌及高等生物都具有的P450酶-CYP51酶的研究进展及其作为靶标来创制筛选新型抑菌活性物的应用前景。
2、首先对木霉菌素倍半萜结构进行“破坏性”的骨架改变,结合生物活性测定,筛选确定了其重要的抑菌活性基团：Δ-9,10(双键)、12,13-环氧结构、C4位的乙酰基,C4位的立体构型：R构型的比S构型的活性好很多。
3、分别在C4位、C8位、C9位和环氧位置进行衍生设计与合成,合成了化合物102个,其中88个是新化合物。所有化合物结构都经过1H NMR、MS,部分经过13C NMR确证结构,每章代表性化合物2.5、2.8、32f、32d、42e和5.1通过X-ray衍射,获得其晶体结构,进一步确定了其化学结构,为后续的小分子化合物与大分子靶标对接打下良好的基础。
4、以《农药生物活性测定标准操作规范(SOP)》为准则,通过生物活性测定,筛选出系列抑菌活性良好的新化合物：在50μg/mL的浓度下,木霉菌素C4位衍生物中,化合物31e、31f和35a对稻瘟病菌的抑制活性明显比木霉菌素原药2.1高,都达到100%抑制率；对黄瓜灰霉病菌的抑制活性：化合物31e、31f和2.1都是100%,35a也达到94.3%的抑制率；2.1对水稻纹枯病菌的活性最高为100%,31e、31f、35a分别为95.5%、92.5%、95.5%；化合物31j和31k对赤霉的抑制率都为100%；化合物31e、35a和木霉菌素2.1对油菜菌核病菌的抑制率为87.7%、86.6%、95.9%。C8位衍生物中,化合物42g对油菜菌核病菌和稻瘟病菌的抑制活性明显都比木霉菌素原药2.1高,抑制率都为100%。C9衍生物中化合物5.1对灰霉菌、稻曲病菌的抑制率为100%。
进一步的初筛、复筛表明：化合物31e、35a、2.1对黄瓜灰霉病菌的EC50值分别4.23、2.99和0.45μg/mL。化合物31e、35a、2.1对油菜菌核病菌的EC50值分别为10.86、12.06、2.20μg/mL。木霉菌素2.1对小麦赤霉病菌的EC50值为5.60μg/mL。化合物31e、31f和35a对稻瘟病菌也表现出良好的生物活性,EC50分别为6.31、12.9和6.00μg/mL,均超过母体木霉菌素的活性。31e、35a、2.1和商品化药剂丙环唑对水稻纹枯病菌的EC50值分别为2.48、4.18、0.72和6.45μg/mL,与丙环唑的毒效比分别为2.60、1.54、8.96。
化合物42g对油菜菌核病菌的EC50值分别1.77μg/mL,高于母体木霉菌素。木霉菌素原药2.1、新化合物42g对稻瘟病病菌的EC50值分别为39.47和0.74μg/mL。化合物42g对稻瘟病菌的抑制活性远超过木霉菌素原药,与现今普遍应用的防治稻瘟病菌的杀菌剂咪鲜胺(EC50=0.98μg/mL)相当,比常规的三环唑和甲基硫菌灵活性要高。另外42g对水稻纹枯病菌的EC50值分别为3.58μg/mL,虽然没有母体木霉菌素的抑制率高,但是也超过了商品化药剂丙环唑(EC50为6.45μg/mL)。42g对水稻稻曲病菌的抑制活性较好,EC50为1.48μg/mL,超过木霉菌素2.1的EC50(2.11μg/mL),比常用的防治稻曲病的常用杀菌剂咪鲜胺(EC50为0.76μg/mL)略低一些。
合成C8位衍生物烯丙位氧化过程中得到了另外一个产物,经1HNMR、MS、X-ray结构确证为C9醛木霉(5.1),经生物测定新颖倍半萜醛化合物5.1对多种植物病原菌活性优异,对黄瓜灰霉的抑制中浓度(EC50)为0.48μg/mL,接近木霉菌素的抑制中浓度0.45μg/mL;对水稻稻瘟病的EC50为11.82μg/mL,高于甲基托布津(EC50为36.72μg/mL),对水稻纹枯病菌的活性EC50为7.40μg/mL,虽然低于木霉菌素母体的活性,但也与丙环唑(EC50=6.45μg/mL)、井冈霉素(EC50为1.26μg/mL)在同一个活性数量级。尤其是对于水稻稻曲病菌的抑制活性很高,EC50为0.80μg/mL,与现在市场上畅销的杀菌剂咪鲜胺(EC50为0.76μg/mL)非常接近,高于母体木霉菌素一个数量级,在稻曲病防治上有一定的开发价值。
5、应用两种不同软件计算log p,比较相互结果发现：C4衍生物中活性好的化合物log P值基本上在2.2到3.2之间,C8位衍生物中对稻瘟病抑制活性好的化合物42g的log P值基本上在3.6-4.0之间。并且通过比较发现用ALOGPS 2.1预测计算一些同分异构体化合物的log P更为精确一些。
6、因为活性化合物5.1在水稻重要病害-稻曲病、纹枯病和稻瘟病防治上显示出良好的活性,化合物42g对水稻稻瘟病防治具有优异的活性,所以进一步研究了其对水生生物-典型大型蚤和栅藻的毒性,通过DS软件预测与实际检测,结果显示42g对大型蚤的毒性都是低毒级别,化合物5.1对大型蚤的毒性预测值与实际测定值都为中等毒性级别,对栅藻的毒性测定值为高毒。所以新颖化合物42g和5.1都可以作为二级先导化合物进一步优化开发或者直接作为潜在活性物用于开发新型倍半萜类广谱高效杀菌剂,具有进一步研究开发的价值。
7、初步研究了活性小分子与CYP51酶的互作机制。采用计算机模拟计算,重点选择细菌、真菌、高等动植物中都很重要的P450家族中CYP51为靶标对象,采用同源建模,选择基因序列最接近的模板建立了灰霉的CYP51蛋白结构-BCCYP51酶,利用Profiles-3D得分值186,应用Autodock 4和DS Libdock对活性化合物分别进行分子对接。结果发现,同样对灰霉模建蛋白CYP51进行对接,不同软件结果一样,母体2.1与活性物5.1在活性口袋中的作用方式与作用位点非常相似,主要结合于HEME所处的活性口袋中央,环氧乙烷指向狭长口袋。小分子的乙酰基和金属铁相互作用。HEME以及金属离子是抑制剂结合的识别作用点。但是42g与5.1的结合方式不同，苯环疏水作用于狭长口袋,倍半萜结构中主要是C8位-丙烯酸酯中的酰基与HEME中的金属铁直接作用。通过小分子化合物与大分子靶标之间的分子对接,初步探讨了活性化合物的作用机制,为进一步的衍生设计打下了良好的基础。
Currently, many novel natural bactericides were developed, such as Validamycin which is a lead compound against Rhizoctonia solani causing many root rots of plants. Series of derivatives from Strobilurin were also developed as high effective, broad-spectrum and safe bactericides based on its original structure modification.
Trichodernia sp. could be a very important endophytic fungus. Recently, we found that the natural product, Trichodermin from this fungus, was able to be against Botrytis cinerea, Rhizoctonia solani and Sclerotinia sclerotiorum with the broad-spectrum, high antifungal activities. Trichodermin would be potentially used as the lead compound for the development of a new generation of industrial fungicides for crop protection by modifying this sesquiterpenoids structure and bioactive assaying, due to its novelty, safety and powerful antifungal molecules. In this thesis, we report the following results:
1) The researches of Trichothecene mycotoxins were systematically reviewed, and the bioactive application, the formation, structure and bioactivities of the secondary metabolite, Trichodermin in an endophytic fungus, Trichodema sp. were also detailly investigated. CYP51, an enzyme of P450 family, widely in bacterium, fungi and other advanced organisms, was used as a target to develop novel antifungal compounds in this study as well.
2) After destroying some moieties of Trichodermin and assaying their bioactivities, the key pharmacophores of this compound was A-9,10,12,13-epoxide moiety and C4-ester.4R-Trichodermin is more active than 4S-Trichodermin.
3) 102 new derivatives of Trichodermin were synthesized by modifying the C4, C8, C9 and epoxide moiety and 88 of them are new compounds. All of these compounds were confirmed by 1H NMR, MS, and compound 2.5,2.8,32f,32d,42e,5.1 were confirmed by X-ray, which will be helpful in studying the structural relationship of small molecular with the target enzyme.
4) According to《Stand operation process of testing pesticidal bioactivity》, a series of novel compounds with good antifungal activities were gotten:at 50μg/mL, compound 31e,31f and 35a have higher activity than lead compound Trichodermin in inhibiting Magnaporthe oryzae. These three compounds also show high bioactivities against B. cinerea and R. solani. Compound 31e,35a and 2.1 inhibit S. sclerotiorum. In the derivatives of C8 of Trichodermin, The inhibition rate of 42g on S. sclerotiorum and M. oryzae is better than that of 2.1. Compound 5.1 has a 100% inhibition on B. cinerea and M. oryzae at 50μg/mL. Further assay indictaed that the EC50 of 31e,35a and 2.1 on B. cinerea is 4.23,2.99 and 0.45μg/mL, respectively, and 10.86,12.0 and 2.20μg/mL on S. sclerotiorum, respectively. The EC50 of 2.1 on Gibberella zeae is 5.60μg/mL. Meanwhile, compound 31e,31f and 3.5a also showed good inbition activity with EC50 6.31,12.9 and 6.00μg/mL on M. oryzae, respectively. The EC50 of 31e,35a,2.1 and Propiconazol on R. solani is up to 2.48,4.18,0.72 and 6.45μg/mL, respectively. Obviously, the bioactivity of 31e,35a and 2.1 on R. solani is several times than Propiconazol.
Interestingly, compound 42g has good potential to develop as a broad-spectrum antifungal pesticide. The EC50 of it on S. sclerotiorum and on M. oyzae is 1.77μg/mL and 0.74μg/mL respectively, which is better than lead compound 2.1. Moreover, the bioactivity of 42g is almost the same as Prochloraz and better than Tricyclazole and Thiophanate methyl. Although the EC50 of 42g is only 3.58μg/mL on R. solani, a little less than 2.1, it is still more active that Propiconazol. And the bioactivity of 42g is also better than 2.1 and almost the same as Prochloraz.
Compound 9-aldehyde Trichodermin (5.1) is another potential antifungal reagent. It was formed by oxidation ofΔ-9,10 with SeO2. This compound showed broad-spectrum antifungal activities and with an EC50 of 0.48μg/mL on B. cinerea. Its EC50 on M. oyzae and R. solani is also up to 11.82μg/mL and 7.40μg/mL respectively, which is a little more active than Thiophanate methyl and almost the same as Propiconazol and Validamycin. More interestingly, its EC50 on Ustilaginoidea virens reaches 0.80μg/mL, almost the same as Prochloraz (EC50,0.76μg/mL) and much better than 2.1. Therefore, 5.1 have the potential to develop as an antifungal reagent on B. cinerea and Ustilaginoidea virens.
5) Two different softwares were used to calculate the log p value and its possible relationship with derivatives' bioactivities. It was found that the log p value range from 2.2 to 3.2 of the derivatives of C4 of Trichodermin which have good antifungal activities. The log p value range from 3.6-4.0 of the C8 derivatives such as 42g.
6) Based on the excellent antifungal activities of 5.1 and 42g against paddy fungi, we further evaluated their toxicities on typical Daphnia magna and Scenedesmus subspicatus. Through DS software calculation and practical evaluation,42g has low toxicity both on Daphnia magna and on Scenedesmus subspicatus; 5.1 has middle toxicity on Daphnia magna and high toxicity on Scenedesmus subspicatus. Thus,42g and 5.1 can be used as new lead compound or even as potential antifungal reagents on paddy fungi for further development.
7) CYP51, which is an enzyme of P450 family and exists widely in bacterium, fungi and other advanced organisms, was used as a target to study the mechanism of small molecular. First, we construct BCCYP51 protein of Botrytis cinerea used by the same enzyme resource model and similar gene sequence. Then to gain a structural understanding and visualize the interaction of the CYP51 protein with compound 2.1, 5.1 and 42g, docking studies were performed using Autodock 4 and Libdock. Although different softwares were used to simulate and calculation 2.1,5.1 and 42g's position in CYP51, the result is the same. Results indicated that lead compound 2.1 and 5.1 have the similar effective manner and action position in target enzyme, but the 42g is different in the position of C8 acrylate. This primary conclusion will help design and prepare novel antifungal pesticides.
木霉菌是植物内生真菌系列中很重要的一类生防菌,木霉菌的广泛应用与其主要代谢产物木霉菌素广谱高效的抑菌活性是分不开的。为了更细致的研究木霉属系列代谢产物,更好的发挥木霉菌的用途,也为了寻求更优异的结构骨架或新颖先导结构,本文以南方红豆杉Taxus chinesis var. mairei内生真菌紫杉木霉Trichoderma taxi sp. nov.菌的代谢产物木霉菌素为先导化合物,根据活性亚结构连接、生物等排性原理等方法,对此类倍半萜结构进行详细的结构修饰,细致的生物活性筛选,具体研究内容及结果如下：
1、系统总结了内生真菌中单端胞霉烯类化合物的研究现状,木霉菌生物防治应用、木霉菌素的发酵、结构、活性,以及细菌、真菌及高等生物都具有的P450酶-CYP51酶的研究进展及其作为靶标来创制筛选新型抑菌活性物的应用前景。
2、首先对木霉菌素倍半萜结构进行“破坏性”的骨架改变,结合生物活性测定,筛选确定了其重要的抑菌活性基团：Δ-9,10(双键)、12,13-环氧结构、C4位的乙酰基,C4位的立体构型：R构型的比S构型的活性好很多。
3、分别在C4位、C8位、C9位和环氧位置进行衍生设计与合成,合成了化合物102个,其中88个是新化合物。所有化合物结构都经过1H NMR、MS,部分经过13C NMR确证结构,每章代表性化合物2.5、2.8、32f、32d、42e和5.1通过X-ray衍射,获得其晶体结构,进一步确定了其化学结构,为后续的小分子化合物与大分子靶标对接打下良好的基础。
4、以《农药生物活性测定标准操作规范(SOP)》为准则,通过生物活性测定,筛选出系列抑菌活性良好的新化合物：在50μg/mL的浓度下,木霉菌素C4位衍生物中,化合物31e、31f和35a对稻瘟病菌的抑制活性明显比木霉菌素原药2.1高,都达到100%抑制率；对黄瓜灰霉病菌的抑制活性：化合物31e、31f和2.1都是100%,35a也达到94.3%的抑制率；2.1对水稻纹枯病菌的活性最高为100%,31e、31f、35a分别为95.5%、92.5%、95.5%；化合物31j和31k对赤霉的抑制率都为100%；化合物31e、35a和木霉菌素2.1对油菜菌核病菌的抑制率为87.7%、86.6%、95.9%。C8位衍生物中,化合物42g对油菜菌核病菌和稻瘟病菌的抑制活性明显都比木霉菌素原药2.1高,抑制率都为100%。C9衍生物中化合物5.1对灰霉菌、稻曲病菌的抑制率为100%。
进一步的初筛、复筛表明：化合物31e、35a、2.1对黄瓜灰霉病菌的EC50值分别4.23、2.99和0.45μg/mL。化合物31e、35a、2.1对油菜菌核病菌的EC50值分别为10.86、12.06、2.20μg/mL。木霉菌素2.1对小麦赤霉病菌的EC50值为5.60μg/mL。化合物31e、31f和35a对稻瘟病菌也表现出良好的生物活性,EC50分别为6.31、12.9和6.00μg/mL,均超过母体木霉菌素的活性。31e、35a、2.1和商品化药剂丙环唑对水稻纹枯病菌的EC50值分别为2.48、4.18、0.72和6.45μg/mL,与丙环唑的毒效比分别为2.60、1.54、8.96。
化合物42g对油菜菌核病菌的EC50值分别1.77μg/mL,高于母体木霉菌素。木霉菌素原药2.1、新化合物42g对稻瘟病病菌的EC50值分别为39.47和0.74μg/mL。化合物42g对稻瘟病菌的抑制活性远超过木霉菌素原药,与现今普遍应用的防治稻瘟病菌的杀菌剂咪鲜胺(EC50=0.98μg/mL)相当,比常规的三环唑和甲基硫菌灵活性要高。另外42g对水稻纹枯病菌的EC50值分别为3.58μg/mL,虽然没有母体木霉菌素的抑制率高,但是也超过了商品化药剂丙环唑(EC50为6.45μg/mL)。42g对水稻稻曲病菌的抑制活性较好,EC50为1.48μg/mL,超过木霉菌素2.1的EC50(2.11μg/mL),比常用的防治稻曲病的常用杀菌剂咪鲜胺(EC50为0.76μg/mL)略低一些。
合成C8位衍生物烯丙位氧化过程中得到了另外一个产物,经1HNMR、MS、X-ray结构确证为C9醛木霉(5.1),经生物测定新颖倍半萜醛化合物5.1对多种植物病原菌活性优异,对黄瓜灰霉的抑制中浓度(EC50)为0.48μg/mL,接近木霉菌素的抑制中浓度0.45μg/mL;对水稻稻瘟病的EC50为11.82μg/mL,高于甲基托布津(EC50为36.72μg/mL),对水稻纹枯病菌的活性EC50为7.40μg/mL,虽然低于木霉菌素母体的活性,但也与丙环唑(EC50=6.45μg/mL)、井冈霉素(EC50为1.26μg/mL)在同一个活性数量级。尤其是对于水稻稻曲病菌的抑制活性很高,EC50为0.80μg/mL,与现在市场上畅销的杀菌剂咪鲜胺(EC50为0.76μg/mL)非常接近,高于母体木霉菌素一个数量级,在稻曲病防治上有一定的开发价值。
5、应用两种不同软件计算log p,比较相互结果发现：C4衍生物中活性好的化合物log P值基本上在2.2到3.2之间,C8位衍生物中对稻瘟病抑制活性好的化合物42g的log P值基本上在3.6-4.0之间。并且通过比较发现用ALOGPS 2.1预测计算一些同分异构体化合物的log P更为精确一些。
6、因为活性化合物5.1在水稻重要病害-稻曲病、纹枯病和稻瘟病防治上显示出良好的活性,化合物42g对水稻稻瘟病防治具有优异的活性,所以进一步研究了其对水生生物-典型大型蚤和栅藻的毒性,通过DS软件预测与实际检测,结果显示42g对大型蚤的毒性都是低毒级别,化合物5.1对大型蚤的毒性预测值与实际测定值都为中等毒性级别,对栅藻的毒性测定值为高毒。所以新颖化合物42g和5.1都可以作为二级先导化合物进一步优化开发或者直接作为潜在活性物用于开发新型倍半萜类广谱高效杀菌剂,具有进一步研究开发的价值。
7、初步研究了活性小分子与CYP51酶的互作机制。采用计算机模拟计算,重点选择细菌、真菌、高等动植物中都很重要的P450家族中CYP51为靶标对象,采用同源建模,选择基因序列最接近的模板建立了灰霉的CYP51蛋白结构-BCCYP51酶,利用Profiles-3D得分值186,应用Autodock 4和DS Libdock对活性化合物分别进行分子对接。结果发现,同样对灰霉模建蛋白CYP51进行对接,不同软件结果一样,母体2.1与活性物5.1在活性口袋中的作用方式与作用位点非常相似,主要结合于HEME所处的活性口袋中央,环氧乙烷指向狭长口袋。小分子的乙酰基和金属铁相互作用。HEME以及金属离子是抑制剂结合的识别作用点。但是42g与5.1的结合方式不同，苯环疏水作用于狭长口袋,倍半萜结构中主要是C8位-丙烯酸酯中的酰基与HEME中的金属铁直接作用。通过小分子化合物与大分子靶标之间的分子对接,初步探讨了活性化合物的作用机制,为进一步的衍生设计打下了良好的基础。
Currently, many novel natural bactericides were developed, such as Validamycin which is a lead compound against Rhizoctonia solani causing many root rots of plants. Series of derivatives from Strobilurin were also developed as high effective, broad-spectrum and safe bactericides based on its original structure modification.
Trichodernia sp. could be a very important endophytic fungus. Recently, we found that the natural product, Trichodermin from this fungus, was able to be against Botrytis cinerea, Rhizoctonia solani and Sclerotinia sclerotiorum with the broad-spectrum, high antifungal activities. Trichodermin would be potentially used as the lead compound for the development of a new generation of industrial fungicides for crop protection by modifying this sesquiterpenoids structure and bioactive assaying, due to its novelty, safety and powerful antifungal molecules. In this thesis, we report the following results:
1) The researches of Trichothecene mycotoxins were systematically reviewed, and the bioactive application, the formation, structure and bioactivities of the secondary metabolite, Trichodermin in an endophytic fungus, Trichodema sp. were also detailly investigated. CYP51, an enzyme of P450 family, widely in bacterium, fungi and other advanced organisms, was used as a target to develop novel antifungal compounds in this study as well.
2) After destroying some moieties of Trichodermin and assaying their bioactivities, the key pharmacophores of this compound was A-9,10,12,13-epoxide moiety and C4-ester.4R-Trichodermin is more active than 4S-Trichodermin.
3) 102 new derivatives of Trichodermin were synthesized by modifying the C4, C8, C9 and epoxide moiety and 88 of them are new compounds. All of these compounds were confirmed by 1H NMR, MS, and compound 2.5,2.8,32f,32d,42e,5.1 were confirmed by X-ray, which will be helpful in studying the structural relationship of small molecular with the target enzyme.
4) According to《Stand operation process of testing pesticidal bioactivity》, a series of novel compounds with good antifungal activities were gotten:at 50μg/mL, compound 31e,31f and 35a have higher activity than lead compound Trichodermin in inhibiting Magnaporthe oryzae. These three compounds also show high bioactivities against B. cinerea and R. solani. Compound 31e,35a and 2.1 inhibit S. sclerotiorum. In the derivatives of C8 of Trichodermin, The inhibition rate of 42g on S. sclerotiorum and M. oryzae is better than that of 2.1. Compound 5.1 has a 100% inhibition on B. cinerea and M. oryzae at 50μg/mL. Further assay indictaed that the EC50 of 31e,35a and 2.1 on B. cinerea is 4.23,2.99 and 0.45μg/mL, respectively, and 10.86,12.0 and 2.20μg/mL on S. sclerotiorum, respectively. The EC50 of 2.1 on Gibberella zeae is 5.60μg/mL. Meanwhile, compound 31e,31f and 3.5a also showed good inbition activity with EC50 6.31,12.9 and 6.00μg/mL on M. oryzae, respectively. The EC50 of 31e,35a,2.1 and Propiconazol on R. solani is up to 2.48,4.18,0.72 and 6.45μg/mL, respectively. Obviously, the bioactivity of 31e,35a and 2.1 on R. solani is several times than Propiconazol.
Interestingly, compound 42g has good potential to develop as a broad-spectrum antifungal pesticide. The EC50 of it on S. sclerotiorum and on M. oyzae is 1.77μg/mL and 0.74μg/mL respectively, which is better than lead compound 2.1. Moreover, the bioactivity of 42g is almost the same as Prochloraz and better than Tricyclazole and Thiophanate methyl. Although the EC50 of 42g is only 3.58μg/mL on R. solani, a little less than 2.1, it is still more active that Propiconazol. And the bioactivity of 42g is also better than 2.1 and almost the same as Prochloraz.
Compound 9-aldehyde Trichodermin (5.1) is another potential antifungal reagent. It was formed by oxidation ofΔ-9,10 with SeO2. This compound showed broad-spectrum antifungal activities and with an EC50 of 0.48μg/mL on B. cinerea. Its EC50 on M. oyzae and R. solani is also up to 11.82μg/mL and 7.40μg/mL respectively, which is a little more active than Thiophanate methyl and almost the same as Propiconazol and Validamycin. More interestingly, its EC50 on Ustilaginoidea virens reaches 0.80μg/mL, almost the same as Prochloraz (EC50,0.76μg/mL) and much better than 2.1. Therefore, 5.1 have the potential to develop as an antifungal reagent on B. cinerea and Ustilaginoidea virens.
5) Two different softwares were used to calculate the log p value and its possible relationship with derivatives' bioactivities. It was found that the log p value range from 2.2 to 3.2 of the derivatives of C4 of Trichodermin which have good antifungal activities. The log p value range from 3.6-4.0 of the C8 derivatives such as 42g.
6) Based on the excellent antifungal activities of 5.1 and 42g against paddy fungi, we further evaluated their toxicities on typical Daphnia magna and Scenedesmus subspicatus. Through DS software calculation and practical evaluation,42g has low toxicity both on Daphnia magna and on Scenedesmus subspicatus; 5.1 has middle toxicity on Daphnia magna and high toxicity on Scenedesmus subspicatus. Thus,42g and 5.1 can be used as new lead compound or even as potential antifungal reagents on paddy fungi for further development.
7) CYP51, which is an enzyme of P450 family and exists widely in bacterium, fungi and other advanced organisms, was used as a target to study the mechanism of small molecular. First, we construct BCCYP51 protein of Botrytis cinerea used by the same enzyme resource model and similar gene sequence. Then to gain a structural understanding and visualize the interaction of the CYP51 protein with compound 2.1, 5.1 and 42g, docking studies were performed using Autodock 4 and Libdock. Although different softwares were used to simulate and calculation 2.1,5.1 and 42g's position in CYP51, the result is the same. Results indicated that lead compound 2.1 and 5.1 have the similar effective manner and action position in target enzyme, but the 42g is different in the position of C8 acrylate. This primary conclusion will help design and prepare novel antifungal pesticides.
引文
1.刘建超；贺红武；冯新民,化学农药的发展方向-绿色化学农药.农药 2005,44,(001),1-3.
2.董文,我国粮食安全现状与科技对策.安徽农业科学 2008,36,(021),9308-9310.
3.刘武成；刘长令,新型高效杀菌剂氟吗啉.农药 2002,41,(001),8-11.
4.杨华铮,农药分子设计.科学出版社：2003.
5.陆春海,ParyleneN的性质预测.工程物理研究院科技年报 2006,,(001),490-491.
6.孙晓红；刘源发,广谱性杀虫剂三唑磷的合成研究.西北大学学报：自然科学版 1996,26,(003),219-223.
7.李华；刘毅锋；张娟；王翠玲；张雄,乙氧甲叉基氨基甲酸酯类的合成研究.精细化工 2003,20,(007),440-442.
8.宣日成；史成华,吡虫啉的合成方法.农药 1998,37,(010),11-14.
9.程敬丽；魏方林；朱烈；赵金浩；朱国念,N-[3-氰基-1-(2,6-二氯-4-三氟甲基苯基)-1H-吡唑-5-基]菊酰胺类化合物的合成及生物活性.有机化学 2008,28,(004),622-627.
10.张国生,吡唑类,吡咯类杀虫剂的研发进展.农药科学与管理 2004,25,(011),23-26.
11.白雪；周成合；米佳丽,三唑类化合物研究与应用.化学研究与应用 2007,19,(007),721-729.
12. Zhao, P. L.; Liu, C. L.; Huang, W.; Wang, Y. Z.; Yang, G. F., Synthesis and fungicidal evaluation of novel chalcone-based strobilurin analogues. J. Agric. Food Chem 2007,55, (14),5697-5700.
13. Huang, W.; Zhao, P. L.; Liu, C. L.; Chen, Q.; Liu, Z. M.; Yang, G. F., Design, synthesis, and fungicidal activities of new strobilurin derivatives. J. Agric. Food Chew 2007,55, (8),3004-3010.
14.Cheng, J. L.; Zhao, J. H.; Zhu, G. N.; Lin, F. C.,-(4-Chlorophenyl)-3-methyl-N-(5-methylthiazol-2-yl) butanamide; Acta Cryst.2009, E65, o184.
15.陈启辉,新型杀菌剂苯噻菌胺.农药 2004,43,(011),515-517.
16.野国中；范志金；李正名；李永红；高发旺；王素华,新磺酰脲类化合物的合成及生物活性.高等学校化学学报 2003,24,(009),1599-1603.
17.刘长令,三唑并嘧啶磺酰胺类除草剂的创制经纬.农药 2002,41,(008),45-46.
18.王辉；陈琼,三唑并嘧啶-2-磺酰胺类除草剂的研究进展.华中师范大学学报：自然科学版 2003,37,(001),68-74.
19.刘长令,嘧啶氧(硫)苯甲酸类除草剂的创制经纬.农药 2002,41,(009),44-45.
20.张一宾,由甲氧丙烯酸酯类抗生素开发农用杀菌剂.农药译丛 1995,17,(003),25-29.
21.柏亚罗,Strobilurins类杀菌剂研究开发进展.农药 2007,46,(005),289-295.
22.陈万义；王龙根；李钟华,新农药的研发-方法.进展.化学工业出版社：2007.
23.张一宾；张怿,世界农药新进展.化学工业出版社：2007.
24.杨吉春；吴峤；刘若霖；马士纯；刘长令,杀菌剂开发的新进展.农药 2008,47,(006),402-405.
25.李海屏,杀菌剂新品种开发进展及发展趋势.江苏化工 2004,32,(006),7-12.
26.汪汉成；祁之秋；王建新；陈长军；周明国,肟菌酯对9种植物病原真菌室内活性测定.农药2006,45,(011),780-781.
27. Brase, S.; Encinas, A.; Keck, J.; Nising, C. F., Chemistry and biology of mycotoxins and related fungal metabolites. Chemical Reviews 2009.,109, (9),3903-3990..
28. Strobel, G. A.; Miller, R. V.; Martinez-Miller, C.; Condron, M. M.; Teplow, D. B.; Hess, W. M., Cryptocandin, a potent antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina. Microbiology 1999,145, (8),1919.
29. Li, J. Y.; Strobel, G.; Harper, J.; Lobkovsky, E.; Clardy, J., Cryptocin, a potent tetramic acid antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina. Org. Lett 2000,2, (6), 767-770.
30. Strobel, G. A.; Dirkse, E.; Sears, J.; Markworth, C., Volatile antimicrobials from Muscodor albus, a .novel endophytic fungus. Microbiology 2001,147, (11),2943.
31. Vicente, M. F.; Cabello, A.; Platas, G.; Basilio, A.; Diez, M. T.; Dreikorn, S.; Giacobbe.R. A.; Onishi, J. C.; Meinz, M.; Kurtz, M. B., Antimicrobial activity of ergokonin A from Trichoderma longibrachiatum. Journal of Applied Microbiology 2001,91, (5),806-813.
32. Wagenaar, M. M.; Clardy, J., Dicerandrols, new antibiotic and cytotoxic dimers produced by the fungus Phomopsis longicolla isolated from an endangered mint. J. Nat.Prod 2001,64, (8), 1006-1009.
33. Li, J. Y.; Harper, J. K.; Grant, D. M.; Tombe, B. O.; Bashyal, B.; Hess, W. M.; Strobel, G. A., Ambuic acid, a highly functionalized cyclohexenone with antifungal activity from Pestalotiopsis spp. and Monochaetia sp. Phytochemistry 2001,56, (5),463-468.
34. Tan, R. X.; Zou, W. X., Endophytes:a rich source of functional metabolites. Natural product reports 2001,18, (4),448-459.
35.李桂玲；王建锋,几种药用植物内生真菌抗真菌活性的初步研究.微生物学通报 2001,28,(006),64-68.
36.兰琪；姬志勤；顾爱国；师宝君；吴文君,苦皮藤内生真菌中杀虫杀菌活性物质的初步研究.西北农林科技大学学报 2004,32,(010),79-84.
37.吴萍茹；马旭闽；方金瑞,车前草内生真菌w-90次级代谢产物的研究.海峡药学 2005,17,(006),116-119.
38.曾松荣；徐倩雯；叶保童；柯野；方白玉；黄晓敏,虎杖内生真菌的分离及产抗菌活性物质的筛选.菌物研究 2005,3,(002),24-26.
39.Rotter, B. A., Invited Review:TOXICOLOGY OF DEOXYNIVALENOL (VOMITOXIN). Journal of Toxicology and Environmental Health 1996,48,(1),1-34.
40. Ueno, Y.,Mode of action of trichothecenes.1977,31,885.
41. DeLoach, J. R.; Gyongyossy-Issa, M.; Khachatourians, G. G., Species-specific hemolysis of erythrocytes by T-2 toxin* 1. Toxicology and Applied Pharmacology 1989,97, (1),107-112.
42. Bra Se, S.; Encinas, A.; Keck, J.; Nising, C. F., Chemistry and biology of mycotoxins and related fungal metabolites. Chem. Rev 2009,109, (9),3903-3990.
43. Ueno, Y., Trichothecenes:chemical, biological and toxicological aspects. Elsevier:1983.
44. Anderson, D. W.; Black, R. M.; Lee, C. G.; Pottage, C.; Rickard, R. L.; Sandford, M. S.; Webber, T. D.; Williams, N. E., Structure-activity studies of trichothecenes:Cytotoxicity of analogues and reaction products derived from T-2 toxin and neosolaniol. Journal of Medicinal Chemistry 1989,32, (3),555-562.
45. Schoerital, R., Trichothecenes, zearalenone, and other carcinogenic metabolites of Fusarium and related microfungi. Advances in cancer research 1985,45,217-290.
46. Freeman, G. G.; Morrison, R. I., The isolation and chemical properties of trichothecin, an antifungal substance from Trichothecium roseum Link. Biochemical journal 1949,44, (1),1.
47. Godtfredsen, W. O.; Grove, J. F.; Tamm, C., Zur Nomenklatur einer neueren Klasse von Sesquiterpenen. Helvetica Chimica Acta 1967,50, (6),1666-1668.
48. Johannisson, A.; Bj Rkhag, B.; Hansson. W.; Gadhasson, I. L.; Thuvander, A., Effects of four trichothecene mycotoxins on activation marker expression and cell proliferation of human lymphocytes in culture. Cell biology and toxicology 1999,15, (4),203-215.
49. Zhou, H. R.; Harkema, J. R.; Hotchkiss, J. A.; Yan, D.; Roth, R. A.; Pestka, J. J., Lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol) synergistically induce apoptosis in murine lymphoid organs. Toxicological Sciences 2000,53, (2),253.
50. Isaka, M.; Punya, J.; Lertwerawat, Y.; Tanticharoen, M.; Thebtaranonth, Y., Antimalarial activity of macrocyclic trichothecenes isolated from the fungus Myrothecium verrucaria. J. Nat. Prod 1999,62, (2),329-331.
51. Garcia, C. C.; Rosso, M. L.; Bertoni, M. D.; Maier, M. S.; Damonte, E. B., Evaluation of the.antiviral activity against Junin virus of macrocyclic trichothecenes produced by the hypocrealean epibiont of Baccharis coridifolia. Planta medica 2002,68, (3),209-212.
52. Ueno, Y.; Hsieh, D., The toxicology of mycotoxins. CRC Critical Reviews in Toxicology 1985,14, (2),99-132.
53. Tamm, C.; Jeker, N., Synthesis of macrocyclic trichothecene mycotoxins. Tetrahedron 1989,45, (8), 2385-2415.
54. Mohr, P.; Tori, M.; Grossen, P.; Herold, P.; Tamm, C., Synthesis of verrucarin A and 3a-hydroxyverrucarin A from verrucarol and diacetoxyscripenol (anguidine). Helv. Chim. Acta 1982, 65,(1412),707.
55. Corley, D. G.; Rottinghaus, G.E.; Tempesta, M. S., Novel trichothecenes from. Tetrahedron Letters 1986,27, (4),427-430.
56. Ziegler, F. E.; Nangia, A.; Schulte, G., Synthesis of the 1,3-dioxolane ring system of the trichothecenes sambucinol and sporol via a stereoselective Claisen rearrangement. Journal of the American Chemical Society 1987,109,(13),3987-3991.
57. Ziegler,F.. F.; Nangia Michael, S., Sporol:A structure revision. Tetrahedron Letters 1988,29, (14), 1665-1668.
58. Ziegler, F. E.; Nangia Gayle, A., The synthesis of neosporol:A trichothecene in search of a natural product. Tetrahedron Letters 1988,29, (14),1669-1672.
59. Ziegler, F. E.; Metcalf III, C. A.; Schulte, G., Confirmation by total synthesis of the revised structure of sporol:an application of cyclic thionocarbonate-initiated radical cyclization. Tetrahedron Letters 1992,33,(22),3117-3120.
60. Ziegler, F. E.; Metcalf III, C. A.; Nangia, A.; Schulte, G., Structure and total synthesis of sporol and neosporol. Journal of the American Chemical Society 1993,115, (7),2581-2589.
61. Ziegler, F. E.; Sobolov, S. B., Synthesis of a highly functionalized carbon ring skeleton for the trichothecene anguidine. Journal of the American Chemical Society 1990,112, (7),2749-2758.
62. Brian, P. W.; Dawkins, A. W.; Grove, J. F.; Hemming, A. G.; Lowe, D., J. Exp. Bot.1961,12,1.
63. Sigg, H. P.; Mauli, R.; E., F.; Hauser, D.,J. Chem. Soc, Chem. Commun.1965,,26.
64. Dawkins, A. W., J. Chem. Soc, Chem. Commun.1965,,27.
65. Colvin, E. W.; Cameron, S., Partial syntheses of the trichothecene mycotoxins, calonectrin and deoxynivaienol. Tetrahedron Letters 1988,29, (4),493-496.
66. Jeker, N.; Mohr, P.; Tamm, C., Conversion of anguidine into calonectrin and 3-deacetyl-calonectrin. Tetrahedron Letters 1984,25, (49),5637-5640.
67. Tulshian, D. B.; Fraser-Reid, B., The ready conversion of anguidine into verrucarol and trichodermol. Tetrahedron Letters 1980,21, (47),4549-4552.
68. Wani, M.C.; Rector, D. H.; Cook, C. E., Synthesis of HT-2 toxin, neosoianiol, T-2 toxin,3'-hydroxy T-2 toxin, and sporotrichiol from anguidine by routes involving hydroxyl inversion/esterification. The Journal of Organic Chemistry 1987,52, (15),3468-3470.
69. McDougal, P. G.; Schmuff, N. R., In Progress in the Chemistry of Organic Natural Products.1985,47, 153.
70. loos, R.; Belhadj,A.; Menez, M.; Faure, A., The effects of fungicides on Fusarium spp. and Microdochium nivale and their associated trichothecene mycotoxins in French naturally-infected cereal grains. Crop Protection 2005,24, (10),894-902.
71. Colvin, E. W.; Malchenko, S.; Raphael, R. A.; Roberts, J. S., Total synthesis of (±)-trichodermin. Journal of the Chemical Society, Perkin Transactions l 1973,1989-1997.
72. Kraus, G. A.; Roth, B.; Frazier, K.; Shimagaki, M., Stereoselective synthesis of calonectrin. Journal of the American Chemical Society 1982,104, (4),1114-1116.
73. Still, W. C.; Tsai, M., Total synthesis of (±)-trichodermol. Journal of the American Chemical Society 1980,102, (10),3654-3655.
74. O'Brien, M.K.; Pearson, A. J.; Pinkerton, A. A.; Schmidt, W.; Willman, K., A total synthesis of (±)-trichodermol. Journal of the American Chemical Society 19.89,111, (4),1499-1501.
75. Trost, B. M.; McDougal, P. G., Total synthesis of verrucarol. Journal of the American Chemical Society 1982,.104, (22),6110-6112.
76. Schlessinger, R. H.; Nugent, R. A., Total synthesis of racemic verrucarol. Journal of the American Chemical Society 1982,104, (4),1116-1118.
77. Roush, W. R.; D'Ambra, T. E., Total synthesis of (±)-verrucarol. Journal of the American Chemical Society 1983,105, (4),1058-1060.
78. Hua, D. H.; Venkataraman, S.; Chan, R. Y. K.; Paukstelis, J. V., Enantioselective total synthesis of (+)-12,13-epoxytrichothec-9-ene and its antipode. Journal of the American Chemical Society 1988, 110, (14),4741-4748.
79. Fujimoto, Y.; Yokura, S.; Nakamura, T.; Morikawa, T.; Tatsuno, T., Total synthesis of 12,13-epoxytrichothec-9-ene. Tetrahedron Letters 1974,15, (29),2523-2526.
80. Anderson, D. W.; Black, R. M.; Lee, C. G.; Pottage, C.; Rickard, R. L.; Sandford, M. S.; Webber, T. D.; Williams, N. E., Structure-activity studies of trichothecenes:cytotoxicity of analogs and reaction products derived from T-2 toxin and neosolaniol. Journal of medicinal chemistry 1989,32, (3), 555-562.
81. Kaneko, T.; Schmitz, H.; Essery, J. M.; Rose, W.; Howell, H. G.; O'Herron, F. A.; Nachfolger, S.; Huftalen, J.; Bradner, W. T., Structural modifications of anguidin and antitumor activities of its analogs. Journal of Medicinal Chemistry 1982,25, (5),579-589.
82. Adler, S. S.; Lowenbraun, S.; Birch, B., Anguidine:A broad phase Ⅱ study of the Southeastern Cancer Study group. Cancer Treatment Reports 1984,68, (2),423-425.
83. DeSimone, P. A.; Greco, F. A.; Lessner, H. F.; Bartolucci, A., Phase Ⅱ evaluation of anguidine (NSC 141537) in 5-day courses in colorectal adenocarcinoma. A Southeastern Cancer Study Group trial. American Journal of Clinical Oncology:Cancer Clinical Trials 1986,9, (3),187-188.
84. Porcher, J. M.; Dahel, C.; Lafarge-Frayssinet, C.; Chu, F. S.; Frayssinet, C., Uptake and metabolism of T-2 toxin in relation to its cytotoxicity in lymphoid cells. Food and Chemical Toxicology 1988,26, (7),587-593.
85. Porcher, J. M.; Lafarge-Frayssinet, C.; Frayssinet, C.; Nurie, A.; Melcion, D.; Richard-Molard, D., Determination of cytotoxic trichothecenes in corn by cell culture toxicity assay. J Assoc Off Anal Chem 1987,70, (5),844-849.
86. Ueno, Y.; Hsieh, D., The toxicology of mycotoxins. CRC Critical Reviews in Toxicology 1985,14, (2),99-132.
87. Robbana-Barnat, S.; Lafarge-Frayssinet, C.; Frayssinet, C., Use of cell cultures for predicting the biological effects of mycotoxins. Cell Biology and Toxicology 1989,5, (2),217-226.
88. Chanh, T. C.; Hewetson, J. F., Structure/function studies of T-2 mycotoxin with a monoclonal antibody. Immunopharmacology 1991,21, (2),83-90.
89. Ramu, A.; Yagen, B.; Ramu, N., The cytotoxicity of T-2 toxin and related 12,13-epoxytrichothecenes to Adriamycin-sensitive and-resistant P388 leukemia cells. Cancer chemotherapy and pharmacology 1989,24, (4),264-267.
90. Godtfredsen, W. O.; Vangedal, S., Trichodermin, a New Sesquiterpene Antibiotic. ACTA CHEMICA SCANDINAVICA 1965,19,1088-1102.
91. Wei, C.; Vaughan, J. R., Mechanism of Action of the Mycotoxin Trichodermin. Proc. Nat. Acad. Sci. USA:1974,71, (3),713-717.
92. Fonzi, W. A.; Sypherd, P. S., Antimicrob. Agents Chemother.1986,29, (4),570-575.
93. Choi, S, U,; Choi,E. J.; Kim, K.H.; Kim, N. Y.; Kwon, B. M.; Kim, S. U.; Bok, S. H.; Lee, S. Y.; Lee, C. O., Cytotoxicity of trichothecenes to human solid tumor cells in vitro. Archives of Pharmacal Research 1996,19, (1),6-11.
94. Mekhancha Dahel. C.; Lafarge F. C.; Venuat A. M., Trichothecenes as antitumoral substances: inhibiting effect on the growth human lymphocytes, lymphoma and leukaemia cells. J. Cell. Pharmacol.1991,2,343-350.
95. Cutler, H. G.; LeFiles, J. H, Trichodermin:Effects on plants. Plant & Cell Physiol.1978,19, (1), 177-182.
96. Adams, P.M.; Hanson, J. R., Sesquiterpenoid metabolites of Trichoderma polysporum and T. sporulosum. Phytochemistry 1972,11, (1),423.
97. Cutler, H. G.; Cle, P. D.; Arrendale, R. F.; Bassfield, R. L.; Cox, R. H., Dendrostilbella sp.(85-25), a new source of trichodermin. Agricultural and Biological Chemistry 1986,50, (10),2667-2668.
98. Ghisalberti, E.L.; Sivasithamparam, K., Antifungal antibiotics produced by Trichoderma spp. Soil Biology and Biochemistry 1991,23, (11),1011-1020.
99. Bamburg; J. R., Biological and biochemical actions of trichothecene mycotoxins. Progress in molecular and subcellular biology 1983,8,41-110.
100. Altomare, C.; Norvell, W. A.; Bjorkman, T.; Harman, G. E., Solubilization of phosphates and micronutrients by the plant-growth-promoting and biocontrol fungus Trichoderma harzianum Rifai 1295-22. Applied and Environmental Microbiology 1999,65, (7),2926-2933.
101. Wiley, Trichoderma-Application, mode of action and potential as a biocontrol agent of soilborne plant pathogenic fungi. Innovative Approaches to Plant Disease Control 1987,,137-160.
102. Papavizas, G. C.; Lewis, J. A., Effect of Gliocladium and Trichoderma on damping-off and blight of snapbean caused by Sclerotium rolfsii in the greenhouse. Plant Pathology 1989,38, (2),277-286.
103. Knaflewski, M.; Ka U Ewicz, A.; Zaworska, A., Charakterystyka u ytkowa i morfologiczna nowych odmian szparaga lekarskiego (Asparagus officinalis L.)[Economic and morphological features of new asparagus (Asparagus officinalis L.) cultivars]. Zeszyty Problemowe Post pow Nauk Rolniczych (Advances of Agricultural Sciences Problem Issues) 497:311-317. In Polish:2004.
104. Pristchepa, L.; Voitka, D.; Kasperovich, E.; Stepanova, N., Influence of Trichodermin-BL on the decrease of fiber flax infection by diseases and the improvement of its production quality. Journal of Plant Protection Research 2006,46, (1),1.
105. Apsite, A.; Svinka, J.;Strikauska, S.; Viesturs,U.; Lisovska, A.; Bicevskis, E.; Svoka,l., The use of trichodermin for plant protection. Proceedings of Agricultural Science 1989,9,114-118.
106. Apsite, A,; Strikauska, S.; Svinka, J.; Vanags, J.; Viesturs, U.; Bicevskis, J.; Lisovska, A. Method for trichodermin production. No.5360,1991.
107. Lewis, J. A.; Papavizas, G. C., Biocontrol of cotton damping-off caused by Rhizoctonia solani in the field with formulations of Trichoderma spp. and Gliocladium virens. Crop Protection 1991,10, (5), 396-402.
108. Apsite, A.; Viesturs, U.; Steinberga, V.; Toma, M., Morphology and antifungal action of the genus Trichoderma cultivated in geometrically dissimilar bioreactors. World Journal of Microbiology and Biotechnology 1998,14, (1),23-29.
109. Apsite, A,;Viesturs, U.; Berzina, G.; Shteinberga, V., Production of the biofungicide trichodermin preparation and its effect upon barley crop.1996.
110. Prischepa, L.; Voitka, D.; Feklistova,I.; Maximova, N., Bioproducts in the control of soil-borne pathogens under cover.1992.
111. Zafari, D.; Koushki, M.:M.; Bazgir, E., Biocontrol evaluation of wheat take-all disease by Trichoderma screened isolates. African Journal of Biotechnology 2008,7, (20),3653-3659.
112.茆振川；侯桂凤,木霉菌对侵染苹果枝条的轮纹病菌的抑制作用.落叶果树 1996,28,(003),6-7.
113.赵蕾,木霉菌的生物防治作用及其应用.生态农业研究 1999,7,(001),66-68.
114.杨依军；齐中波,拮抗木霉菌在生物防治中的作用.天津农业科学 2000,6,(003),29-33.
115.王革；李梅云,木霉菌对烟草黑胫病菌的拮抗机制及其生物防治研究.云南大学学报：自然科学版 2001,23,(003),222-226.
116.高克祥；郭润芳,木霉菌对五种植物病原真菌的重寄生作用.山东农业大学学报：自然科学版 2002,33,(001),37-42.
117.吴石平；燕嗣皇,施肥及栽培方法对木霉菌在辣椒上的促生增产效应的影响.贵州农业科学2002,30,(004),13-15.
118.邵红涛；许艳丽；李春杰；李兆林,筛选用于防治大豆尖孢镰刀菌根腐病的木霉菌株.中国油料作物学报 2004,26,(004),74-77.
119.黄艳青；庄敬华；高增贵；徐韶；陈捷：木霉菌诱导甜瓜抗枯萎病相关防御反应酶系的研究.沈阳农业大学学报 2005,36,(005),546-549.
120.庄敬华；陈捷；杨长成；高增贵；刘限；牟连晓；郑雅楠,生防木霉菌生物安全性评价.中国农业科学 2006,39,(004),715-720.
121.于新；田淑慧；徐文兴；刘开启,木霉菌生防作用的生化机制研究进展.中山大学学报：自然科学版 2005,44(002),86-90.
122.俞晓平；陈列忠；申屠旭萍,植物内生菌及其代谢物在生物农药创制中的应用.浙江农业学报2006,18,(005),289-293.
123.石一珺；申屠旭萍；俞晓平,木霉菌素产生菌的诱变育种.安徽农业科学 2008,36,(029),12806-12807.
1.24.石一珺；申屠旭萍；俞晓平,1株枸骨内生真菌菌株的分类鉴定及其代谢产物的生防作用研究.植物病理学报 2009,,(004),362-367.
125.章初龙；徐同,木霉属组和Pachybasium组的分子系统学研究.菌物系统 2002,21,(4),538-546.
126.章初龙；徐同,Trichoderma harzianum及其近缘种的分子系统学研究.生物多样性 2003,11,(001),10-19.
127.章初龙；徐同,我国河北,浙江,云南及西藏木霉种记述.菌物学报 2005,24,(002),184-192.
128.章初龙；王国平；郑必强；陈绍瑗；林福呈,紫杉木霉ZJUF0986抗真菌活性代谢产物分离提取及其活性研究.菌物学报 2008,27,(003),439-446.
129.王国平；鲁书玲；郑必强；章初龙,紫杉木霉ZJUF0986代谢产物及其对番茄灰霉病的抑制作用.浙江农业学报 2008,20,(002),104-108.
130. Zhang, C. L.; Liu, S.; Lin, F. C.; Kubicek, C. P.; Druzhinina, I. S., Trichoderma taxi sp. nov., an endophytic fungus from Chinese yew Taxus mairei. FEMS microbiology letters 2007,270, (1),90-96.
131.林福呈；章初龙；陈绍瑗,一种紫杉木霉菌株及其在制备木霉菌酯素中的用途.CN101113414,2007.
132. Shao-Yuan, C.; Chu-Long, Z.; Yu-Zhe, C.; Fu-Cheng, L., Trichodermin (4β-acetoxy-12,13-epoxytrichothec-9-ene). Acta. Cryst. E 2008, E64, o702.
133.袁志林；陈益存；章初龙；林福呈；陈连庆,中国木霉属内生真菌一个新记录种Trichoderma chlorosporum.菌物学报 2008,27,4.
134.王国平；郑必强；章初龙；林福呈,木霉菌酯素的提纯方法.CN101168758,2007.
135.王国平；郑必强；章初龙；林福呈,发酵生产木霉菌酯素的方法及所用的发酵培养基.CN101168757,2007.
136. Tanford, C., How protein chemists learned about the hydrophobic factor. Protein Science 1997,6, (6), 1358-1366.
137. Montal, M.; Mueller, P., Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties. Proceedings of the National Academy of Sciences of the United States of America 1972,69, (12),3561.
138. Dill, K. A., Dominant forces in protein folding. Biochemistry 1990,29, (31),7133-7155.
139. Kubinyi, H.; Folkers, G.; Martin, Y. C.,3D QSAR in drug design:Recent advances. Springer Netherlands:1998.
140. Kubinyi, H., QSAR and 3D QSAR in drug design Part 1:methodology. Drug Discovery Today 1997, 2, (11),457-467.
141. Wold, S.; Johansson, E.; Cocchi, M.,3D QSAR in drug design:theory, methods and applications. PLS-Partial Least Squares Projection to Latent Structures. ESCOM, Lieden 1993,,523-550.
142. Cramer, R. D.; DePriest, S. A.; Patterson, D. E.; Hecht, P., In 3D QSAR in drug design:Theory, Methods, and Applications. Leiden:ESCOM 1993,443,485.
143.苏笠；杨劲；王友群；王广基,化合物脂水分配系数计算软件及比较研究.中国药科大学学报2008,39,(002),178-182.
144.王连生,分子结构性质与活性.化学工业出版社：1997.
145. Lodge, K. B., Octanol-Water Partition Coefficients of Cyclic C-7 Hydrocarbons and Selected Derivatives. J. Chem. Eng. Data 1999,44, (6),1321-1324.
146. Edelbach, D. J.; Lodge, K. B., Insights into the measurement of the octanol-water partition coefficient from experiments with acrylate esters. Physical Chemistry Chemical Physics 2000,2, (8),1763-1771.
147. Finizio, A.; Vighi, M.; Sandroni, D., Determination of n-octanol/water partition coefficient (Kow) of pesticide critical review and comparison of methods. Chemosphere 1997,34, (1),131-161.
148.Eadsforth, C. V.; Moser, P., Assessment of reverse-phase chromatographic methods for determining partition coefficients. Chemosphere 1983,12, (11-12),1459-1475.
149.陈凯先；蒋华良；嵇汝运,计算机辅助药物设计—原理,方法药及应用.上海：上海科技出版社：2001.
150.(?)黄青春,杀菌剂作用机制的最新研究进展.世界农药 2006,28,(001),10-15.
151.刘斌；(?)飞；姚建华；廖泉；范波涛；杀菌剂,除草剂和杀虫剂的先导筛选规则.农药学学报(?)(003),220-228.
152.张礼和,从生物有机化学到化学生物学.化学进展 2004,16,(002),313-318.
153.沈旭；蒋华良；余长缨；陈莉莉,小分子与蛋白质靶分子相互作用研究方法及应用.化学生物学进展，化学工业出版社：2005；498-529.
154 I (?)ey, D., Molecular recognition of DNA structure by proteins that mediate genetic recombination. Journal of Molecular Recognition 1994,7, (2),71-78.
155. (?). S. S.; Mayo, M. W.; Bruno, J. G.; Bronk, B. V.; Batt, C. A.; Chambers, J. P., A review of molecular recognition technologies for detection of biological threat agents. Biosensors and Bioelectronics 2000,15, (11-12),549-578.
156. Vogel, V.; Thomas, W. E.; Craig, D. W.; Krammer, A.; Baneyx, G., Structural insights into the mechanical regulation of molecular recognition sites. Trends in biotechnology 2001,19, (10), 416-423.
157.吴会灵；杨原；张重杰；何锡文,小分子与核酸相互作用的研究进展.分析化学(FENXI HUAXUE) 2004,32.
158.李锐；任海平；孙艳亭；姚英艳；卢奎,小分子与生物大分子间非共价相互作用分析方法研究进展.分析化学 2006,6,(12).
159. Vajda, S.; Camacho, C. J., Protein-protein docking:is the glass half-full or half-empty. TRENDS in Biotechnology 2004,22, (3),110-116.
160. Smith, G. R.; Sternberg, M. J. E., Prediction of protein-protein interactions by docking methods. Current Opinion in Structural Biology 2002,12, (1),28-35.
161. Smith, G. R.; Sternberg, M. J. E.; Bates, P. A., The Relationship between the Flexibility of Proteins and their Conformational States on Forming Protein-Protein Complexes with an Application to Protein-Protein Docking. Journal of Molecular Biology 2005,347, (5),1077-1101.
162. Abagyan, R.; Totrov, M., High-throughput docking for lead generation. Current Opinion in Chemical Biology 2001,5, (4),375-382.
163.田青.二噁英类环境毒素及其抑制剂的分子对接和定量构效关系研究.同济大学,2008.
164. Lengauer, T.; Rarey, M., Computational methods for biomolecular docking. Current opinion in structural biology 1996,6, (3),402-406.
165.梁赤周.抗三唑磷基因工程抗体的研制及同源建模.浙江大学,2010.
166.刘飞；黄青春,杀菌剂作用机制的最新研究进展.世界农药 2006,28,(001),10-15.
167.思彬彬；杨卓,甲氧基丙烯酸酯类杀菌剂作用机理研究进展.世界农药 2007,29,(006),5-9.
168.闫晓静；金淑惠；陈馥衡；王道全,Strobilurin类杀菌剂作用靶标的研究进展.农药学学报 2006,8,(004),299-305.
169.安田康,新杀菌剂的靶标和先导化合物的探索.农药译丛 2000,13,(3),1-1.
170.阎隆飞；孙之荣,蛋白质分子结构.清华大学出版社：1999.
171. De Groot, M. J., Designing better drugs:predicting cytochrome P450 metabolism. Drug discovery today 2006,11,(13-14),601-606.
172. Kelly, S. L.; Lamb, D. C.; Kelly, D. E., Cytochrome P450 biodiversity and biotechnology. Biochemical Society Transactions 2006,34,1159-1160.
173. Lepesheya, G. I.; Waterman,M. R., Sterol 14 [alpha]-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms. Biochimica et Biophysica Acta (BBA)-General Subjects 2007,1770, (3),467-477.
174. Waterman, M. R.; Lepesheva, G. I., Sterol 14 [alpha]-demethylase, an abundant and essential mixed-function oxidase. Biochemical and biophysical. research communications 2005,338, (1), 418-422.
175. Fiecchi, A.; Kienle, M. G.; Scala, A.; Galli, G.; Paoletti, E. G.; Cattabeni,F.; Paoletti, R., Hydrogen exchange and double bond formation in cholesterol biosynthesis. Proceedings of the Royal Society of London. Series B, Biological Sciences 1972,180, (1059),147-165.
176. Mitropoulos, K. A.; Gibbons, G.F.; Reeves, B. E. A., Lanosterol 14a-demethylase. similarity of the enzyme system from yeast and rat liver. Steroids 1976,27, (6),821-829.
177. Akhtar, M.;Alexander, K.; Boar, R. B., Chemical and enzymic studies on the characterization of intermediates during the removal of the 14 alpha-methyl group in cholesterol biosynthesis. The use of 32-functionalized lanostane derivatives. Biochem J.1978,169, (3),449-463.
178. Gibbons, F. G.; Pullinger, C. R.; Mitropoulos, K. A., Studies on the mechanism of lanosterol 14 alpha-demethylation. A requirement for two distinct types of mixed-function-oxidase systems. Biochem J.1979,183, (2),309-315.
179. Trzaskos, J. M.; Bowen, W. D.; Shafiee, A.; Fischer, R. T.; Gaylor, J. L., Cytochrome P-450-dependent oxidation of lanosterol in cholesterol biosynthesis. Microsomal electron transport and C-32 demethylation. Journal of Biological Chemistry 1984,259, (21),13402.
180. Yoshida, Y.; Aoyama, Y., Yeast cytochrome P-450 catalyzing lanosterol 14 alpha-demethylation. I. Purification and spectral properties. Journal of Biological Chemistry 1984,259, (3).1655.
181. Kalb, V. F.; Loper, J. C.; Dey, C. R.; Woods, C. W.; Sutter, T. R., Isolation of a cytochrome P-450 structural gene from Saccharomyces cerevisiae. Gene 1986,45, (3),237-245.
182. Nebert, D. W.; Nelson, D. R.; Coon, M. J.; Estabrook, R. W., The P450 superfamily:update on new sequences, gene mapping, and recommended nomenclature. DNA and Cell Biology 1991,10, (1), 1-14.
183. Aoyama, Y.; Horiuchi, T.; Gotoh,O.; Noshiro, M.; Yoshida, Y., CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to eukaryotic CYP51. Journal of biochemistry 1998,124, (4),694-696.
184. Trzaskos, J.; Kawata, S.; Gaylor, J. L., Microsomal enzymes of cholesterol biosynthesis. Purification of lanosterol 14 alpha-methyl demethylase cytochrome P-450 from hepatic microsomes. Journal of Biological Chemistry 1986,261, (31),14651.
185. Kahn, R. A.; Bak, S.; Olsen, C. E., Isolation and reconstitution of the heme-thiolate protein obtusifoliol 14 alpha-demethylase from Sorghrum bicolor. JBiol. Chem.1996,271, (51), 32944-32950.
186. Bellamine, A.; Mangla, A. T.; Nes, W. D., Characterization and catalytic properties of the sterol 14 alpha-demethylase from Mycobacterium tuberculosis actually encodes a p450 similar to eukaryotic cyp51. Proc Natl Acad Sci USA 1999,96, (16),8937-8942.
187. Ji, H.; Zhang, W.; Zhou, Y.; Zhang, M.; Zhu, J.; Song, Y.; Lu, J.; Zhu, J., A Three-Dimensional Model of Lanosterol 14 [alpha]-Demethylase of Candida albicans and Its Interaction with Azole Antifungals. J. Med. Chem 2000,43, (13),2493-2505.
188. Kelly, S.; Lamb, D.; Cannieux, M.; Greetham, D.; Jackson, C.; Marczylo, T.; Ugochukwu, C.; Kelly, D., An old activity in the cytochrome P450 superfamily (CYP51) and a new story of drugs and resistance. Biochemical Society Transactions 2001,29,122-128.
189. Lepesheva, G. I.; Waterman, M. R., CYP51--the omnipotent P450. Molecular and cellular endocrinology 2004,215, (1-2),165-170.
190.杨娇艳；杨劭,稻瘟病菌(Magnaporthe grisea)14α-去甲基化酶与抑制剂的结合特性与新型杀真菌剂筛选.2008,1-10.
191. Aoyama, Y., Recent progress in the CYP51 research focusing on its unique evolutionary and functional characteristics as a diversozyme P450. Front. Biosci 2005,10,1546-1557.
192. Nelson, D. R., Cytochrome P450 and the individuality of species. Archives of Biochemistry and Biophysics 1999,369, (1),1-10.
193. Lepesheva, G. L.; Virus, C.; Waterman, M. R., Conservation in the CYP51 Family. Role of the B Helix/BC Loop and Helices F and G in Enzymatic Function. Biochemistry 2003,42, (30),9091-9101.
194. Holtje, H, D.; Fattorusso, C., Construction of a model of the Candida albicans lanosterol 14-[alpha]-demethylase active site using the homology modelling technique. Pharmaceutica Acta Helvetiae 1998,72, (5),271-277.
195. Poulos, T. L.; Finzel, B. C.; Howard, A. J., High-resolution crystal structure of cytochrome P450cam 1. Journal of molecular biology 1987,195, (3),687-700.
196. Hasemann, C. A.; Ravichandran, K. G.; Peterson, J. A.; Deisenhofer, J., Crystal structure and refinement of cytochrome P450terp at 2.3 A resolution* 1. Journal of molecular biology 1994,236, (4),1169-1185.
197. Cupp-Vickery, J. R.; Poulos, T. L., Structure of cytochrome P450 eryF involved in erythromycin biosynthesis. Nature Structural & Molecular Biology 1995,2, (2),144-153.
198. Ravichandran, K. G.;Boddupalli, S. S.; Hasermann, C. A.; Peterson, J. A.; Deisenhofer, J., Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's. Science 1993, 261,(5122),731-736.
199. Ruge, E.; Korting, H. C.; Borelli, C., Current state of three-dimensional characterisation of antifungal targets and its use for molecular modelling in drug design. International journal of antimicrobial agents 2005,26, (6),427-441.
200.徐铮；曹永兵,麦角甾醇生物合成途径中的抗真菌药作用靶酶.国外医药：抗生素分册 2001,22,(005),193-197.
201. Tuck, S. F.; Patel, H.; Safi, E.; Robinson, C. H., Lanosterol 14 alpha-demethylase (P45014DM): effects of P45014DM inhibitors on sterol biosynthesis downstream of lanosterol. Journal of lipid research 1991, 32, (6),893.
202.王国平；郑必强；章初龙；林福呈木霉菌素测定方法及用途.CN101144808,2007.
203. Shima, J.; Takase, S.; Takahashi, Y.; Iwai, Y.; Fujimoto, H.; Yamazaki, M.; Ochi, K., Novel detoxification of the trichothecene mycotoxin deoxynivalenol by a soil bacterium isolated by enrichment culture. Applied and environmental microbiology 1997,63, (10),3825.
204. Choi, S. U.; Choi, E. J.; Kim, K. H.; Kim, N. Y.; Kwon, B. M.; Kim, S. U.; Bok, S. H.; Lee, S. Y.; Lee, C.O., Cytotoxicity of trichothecenes to human solid tumor cells in vitro. Archives of Pharmacal Research 1996,19, (1),6-11.
205. Anderson, D. W.; Black, R. M.; Lee, C. G.; Pottage,C.; Rickard, R. L.; Sandford, M. S.; Webber, T. D.; Williams, N. E., Structure-activity studies of trichothecenes:cytotoxicity of analogs and reaction products derived from T-2 toxin and neosolaniol. Journal of medicinal chemistry 1989,32, (3), 555-562.
206. Bamburg, J. R., Biological and biochemical actions of trichothecenes mycotoxins. In Progress in molecular and subcellular biology 8, Springer Verlag,:Berlin,1983; 41-110.
207. Mekhancha-Dahel, C.; Lafarge-Frayssinet, C.; Venuat, A. M.; Rosenfeld, C.; Frayssinet, C., Trichothecenes as antitumoral substances:inhibiting effect on the growth human lymphocytes, lymphoma and leukaemia cells. J. Cell. PharmacoL 1991,2,343-350.
208. Melmed, R. N.; Ishai-Michaeli, R.; Yagen, B., Differential inhibition by T-2 toxin of total protein, DNA and isoprenoid synthesis in the culture macrophage cell line J774. Biochemical pharmacology 1985,34, (15),2809-2812.
209. Rosenstein, Y.; Lafarge-Frayssinet, C., Inhibitory effect of Fusarium T-2 toxin on lymphoid DNA and protein synthesis. Toxicol. Appl. Pharmacol.1983,70,283-288.
210. Uenoy Y.; Nakajima, M.; Sakai, K.; Ishii, K.; Sato, N.; Shimada, N., Inhibition of protein synthesis in animal cells. J. Biochem.1973,74,285-296.
211. Cheng, J. L.; Zhou, Y.; Zhao, J. H.; Zhang, C. L.; Lin, F. C., Synthesis and antifungal activity of trichodermin derivatives. Chinese Chemical Letters 2010,21, (09),1037-1040.
212. Fonzi, W. A.; Sypherd, P. S., Trichodermin esterase activity and trichodermin resistance in Mucor racemosus. Antimicrobial agents and chemotherapy 1986,29, (4),570-575.
213.Lucas, H. J.; Schlatter, M. J.; Jones, R. C., The Isomeric 2,3-Epoxypentanes and 2-Pentenes. The Extent to which Mixtures of Diastereomers Are Formed in Reactions of Some Pentane Compounds. Journal of the American Chemical Society 1941,63, (1),22-28.
214. Gelbard, G.; Brunelet, T.; Jouitteau, C., Oxydation d'alcools par l'anhydride chromique dans les conditions du transfert de phase solide-liquide. Tetrahedron Letters 1980,21, (48),4653-4654.
215. Cheng, J. L.; Zhou, Y,; Lin, F. C.; Zhao, J. H.; Zhu, G. N., Trichodermol (4\a-hydroxy-12,13-epoxytrichothec-9-ene). Acta. Cryst. E 2009,65, (o2897).
216. Zhang, C.; Liu, S.; Lin, F.; Kubicek, C. P.; Druzhinina, I. S., Trichoderma taxi sp. nov., an endophytic fungus from Chinese yew Taxus mairei. FEMS microbiology letters 2007,270, (1),90-96.
217. Fr Patent 1,508,066 (Written In French),1968.
218.李述文,范如霖.实用有机化学手册 上海：上海科学技术出版社 1981,12,210.
219. Kaneko, T.; Schmitz, H.; Essery, J. M.; Rose, W.; Howell, H. G.; O'Herron, F. A.; Nachfolger, S.; Huftalen, J.; Bradner, W. T., Structural modifications of anguidin and antitumor activities of its analogs. Journal of Medicinal Chemistry 1982,25, (5),579-589.
220. Choi, S. U.; Choi,E. J.; Kim, K. H.; Kim, N. Y.;Kwon, B. M.; Kim, S. U.; Bok, S. H.; Lee, S. Y.; Lee, C. O., Cytotoxicity of trichothecenes to human solid tumor cells in vitro. Archives of Pharmacal Research 1996,19, (1),6-11.
221. PROCESS-AUTO, A., Processing Package for Imaging Plate Diffractometer. Rigaku Corporation, Tokyo 1998,,.
222. May, J. J.;.Kessler, N.; Marahiel, M. A.; Stubbs, M. T., Crystal structure of DhbE, an archetype for aryl acid activating domains of modular nonribosomal peptide synthetases. Proceedings of the National Academy of Sciences of the United States of America 2002,99, (19),12120.
223. Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A., Completion and refinement of crystal structures with SIR92. Journal of Applied Crystallography 1993,26, (3),343-350.
224. Sheldrick, G. M., A short history of SHELX. Acta Crystallographica Section A:Foundations of Crystallography 2007,64, (1),112-122.
225.Farrugia, L.J., ORTEP-3 for Windows-a version of ORTEP-Ⅲ with a Graphical User Interface (GUI). Journal of Applied Crystallography 1997,30, (5),565.
226. Watkin, D. J.; Prout, C. K.; Carruthers, J. R.; Betteridge, P. W., CRYSTALS. Issue 10. Chemical Crystallography Laboratory. In Oxford, England:1996.
227. Spek, A. L., Structure validation in chemical crystallography. Acta Crystallographica Section D: Biological Crystallography 2009,65, (2),148-155.
228. Clough, J. M.; Godfrey, C.; Hudson, D. H.; Miyamoto, J., Fungicidal Activity:Chemical and Biological Approaches to Plant Protection. In John Wiley & Sons, Ltd Chichester, UK:1998; 109-148.
229. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 1997,23, (1-3),3-25.
230. Clark, D. E.; Pickett, S. D., Computational methods for the prediction of[] drug-likeness'. Drug Discovery Today 2000,5, (2),49-58.
231. Tice, C. M., Selecting the right compounds for screening:does Lipinski's Rule of 5 for pharmaceuticals apply to agrochemicals?. Pest management science 2001,57, (1),3-16.
232. Tice, C. M., Selecting the right compounds for screening:use of surface-area parameters. Pest management science 2002,58, (3),219-233.
233.刘斌；俞飞；姚建华；廖泉；范波涛,杀菌剂,除草剂和杀虫剂的先导筛选规则.农药学学报2007,9,(003),220-228.
234. Zheng, X.; Li, Z.; Wang, Y.; Chen, W.; Huang, Q.; Liu, C.; Song, G., Syntheses and insecticidal activities of novel 2,5-disubstituted 1,3,4-oxadiazoles. Journal of Fluorine Chemistry 2003,123, (2), 163-169.
235. Janicka, M.; O Cik-Mendyk, B.; Tarasiuk, B., Planar chromatography in studies of the hydrophobic properties of some new herbicides. JPC-Journal of Planar Chromatography-Modern TLC 2004,17, (3),186-191.
236. http://www.vcclab.org.
237. http://www.acdlabs.com.
238. Zhao, J. H.; Zhou, Y.; Zhang, J. G.; Cheng, J. L.; Lin, F. C., Dihalogenated Trichodermin (4-\β-Acetoxy-9,10-dibromo-12,13-epoxytrichothec). Acta Cryst.E 2010,66, o210.
239. Plattbe, R. D.; Al-Hetti, M. B.; Weisleder, D.; Sinclair, J. B., A New Trichothecene from Trichothecium roseum. J. Chem. Research (M) 1988,,2461-2473.
240.张红；陈夕军；童蕴慧；纪兆林；徐敬友,纹枯病菌胞壁降解酶对水稻组织和细胞的破坏作用.扬州大学学报：农业与生命科学版 2005,26,(004),83-86.
241.孟庆忠；刘志恒,水稻纹枯病研究进展.沈阳农业大学学报 2001,32,(005),376-381.
242.张穗；肖培英；温广月；曹黎明,氟铃脲对水稻纹枯病菌的毒力和作用机制.植物保护学报 2007,34,(001),87-90.
243.赵丽静；杨晓楠；李祥英；刘峰,11种杀菌剂对水稻纹枯病菌的毒力比较.农药研究与应用2009,,(005),27-29.
244. Ahn, Y. M.; Vander Velde, D. G.; Georg, G.l., Synthetic Studies with 13-Deoxybaccatin Ⅲ. J. Org. Chem 2002,67, (20),7140-7143.
245. Wani, M. C.; Rector, D. H.; Cook, C. E., Synthesis of HT-2 toxin, neosolaniol, T-2 toxin,3'-hydroxy T-2 toxin, and sporotr-ichiol from anguidine by routes involving hydroxyl inversion/esterification. The Journal of Organic Chemistry 1987,52, (15),3468-3470.
246. Stephenson, L. M.; Speth, D. R., Mechanism of allylic hydroxylation by selenium dioxide. The Journal of Organic Chemistry 1979,44, (25),4683-4689.
247. Davidse, L. C., Benzimidazole fungicides:mechanism of action and biological impact. Annual review of phytopathology 1986,24, (1),43-65.
248.潘以楼；汪智渊,油菜菌核病菌对多菌灵的抗药性.中国油料 1997,19,(003),67-68.
249.张夕林；张治；张建明；张谷丰；孙雪梅,多菌灵防治油菜菌核病药效下降原因及综防对策.农药科学与管理 1998,67,(3),15-17.
250.方中达,植病研究方法：第三版.北京：中国农业出版社：1996.
251.裴华；凌忠专,辽宁丹东地区稻瘟病菌生理研究.植物病理学报 1986,16,(4),197-203.
252. Baker, B.; Zambryski, P.; Staskawicz, B.; Dinesh-Kumar, S. P., Signaling in plant-microbe interactions. Science 1997,276,(5313),726-733.
253.周光召；中国科协学术年会,面向21世纪的科技进步与社会经济发展.中国科学技术出版社：1999.
254.孙漱沅；孙国昌,我国稻瘟病研究的现状和展望.植保技术与推广 1996,16,(003),39-40.
255. Kraus, G. A.; Thomas, P. J., Synthesis of 7,7,8-trideuteriated trichothecenes. The Journal of Organic Chemistry 1988,53, (7),1395-1397.
256. Yun, S. Y.; Zheng, J. C.; Lee, D., Stereoelectronic Effect for the Selectivity in C-H Insertion of Alkylidene Carbenes and Its Application to the Synthesis of Platensimycin. Journal of the American Chemical Society 2009,131, (24),8413-8415.
257. Curley Jr, R. W.; Ticoras, C. J., Stereospecific synthesis of the important retinoid synthon ethyl trans-3-formyl-2-butenoate via direct two-stage oxidation of ethyl 3-methyl-2-butenoate. The Journal of Organic Chemistry 1986,51, (2),256-258.
258.谭亚军；李少南；吴小毛,几种杀虫剂对大型蚤的慢性毒性.农药学学报 2004,6,(003),62-66.
259.沈国兴；严国安,农药对藻类的生态毒理学研究：Ⅱ.毒性机理及其富集和降解.环境科学进展1999,7,(006),131-140.
260. Trachtenberg, E. N.; Carver, J. R., Stereochemistry of selenium dioxide oxidation of cyclohexenyl systems. The Journal of Organic Chemistry 1970,35, (5),1646-1653.
261. Brown, H. C.; Dhokte, U. P., Hydroboration.90. Synthesis of 2-Isobutyl-and 2-Isopropylapopinenes. Rates and Stoichiometry of the Hydroboration of 2-Organylapopinenes with Borane-Methyl Sulfide and Borane-Tetrahydrofuran. The Journal of Organic Chemistry 1994,59, (8),2025-2032.
262. Fattorusso, E.; Romano, A.; Taglialatela-Scafati, O.; Irace, C.; Maffettone, C.; Bavestrello, G.; Cerrano, C., Oxygenated cembranoids of the decaryiol type from the Indonesian soft coral Lobophytum sp. Tetrahedron 2009,65, (15),2898-2904.
263. Jones, T. K.; Chu, L.; Mrozik, H.; Slayton, L.; Rafalko, B.; Goldmann, M. L.; Shoop, W. L. Margiatto, G.; Fisher, M. H., Synthesis and biological activity of 4a,4"-disubstituted avermectins. Journal of Agricultural and Food Chemistry 1994,42, (8),1786-1790.
264. Huffman, J. W.; Bushell, S. M.; Miller, J.; Wiley, J. L.; Martin, B. R.,1-Methoxy-, 1-deoxy-11-hydroxy-and 11-Hydroxy-l-methoxy-[Delta] 8-tetrahydrocannabinols:new selective ligands for the CB2 receptor. Bioorganic & medicinal chemistry 2002,10, (12),4119-4129.
265.林琳；叶正和；高同春,水稻稻曲病菌药剂室内生物测定和筛选.安徽农业科学 2008,36,(004),1482-1483.
266.蔡祝南；吴蔚文；高君川,水稻病虫害防治[M1.北京：金盾出版社：1997.
267.缪巧明；李化瑶,云南省稻曲病研究进展.云南农业科技 1994,3,8-10.
268.王疏；周永力,稻曲病菌的病原学.植物病理学报 1998,28,(001),19-24.
269. Goodsell, D. S.; Olson, A. J., Automated docking of substrates to proteins by simulated annealing. Proteins:Structure, Function, and Bioinformatics 1990,8, (3),195-202.
270. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J., Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of Computational Chemistry 1998,19, (14),1639-1662.
271. Diego, S., Affinity user guide. MSI Inc.:USA,2002.
272. Marti-Renom, M. A.; Stuart, A.; Fiser, A., S nchez, R., Melo, F. and Sali, A.(2000) Comparative protein structure modeling of genes and genomes. Annu. Rev. Biophys. Biomol. Struct 29,291-325.
273. Sali, A.; Blundell, T. L., Comparative protein modelling by satisfaction of spatial restraints. Protein Structure by Distance Analysis 1994,,64-86.
274. Fiser, A.; Do, R.; Ali, A., Modeling of loops in protein structures. PRS 2000,9, (09),1753-1773.
275. Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M., PROCHECK:a program to check the stereochemical quality of protein structures. Journal of Applied Crystallography 1993,26, (2),283-291.
276. Pearson, W. R.; Lipman, D. J., Improved tools for biological sequence comparison. Proceedings of the National Academy of Sciences 1988,85, (8),2444.
277. Ito, A.; Sudo, K.; Kumazawa, S.; Kikuchi, M.; Chuman, H. In Three-Dimensional Modeling of Cytochrome P450 14α-Demethylase (CYP51) and Interaction ofAzole Fungicide Metconazole with CYP51,2005; ACS Publications:2005; 142-150.
2.董文,我国粮食安全现状与科技对策.安徽农业科学 2008,36,(021),9308-9310.
3.刘武成；刘长令,新型高效杀菌剂氟吗啉.农药 2002,41,(001),8-11.
4.杨华铮,农药分子设计.科学出版社：2003.
5.陆春海,ParyleneN的性质预测.工程物理研究院科技年报 2006,,(001),490-491.
6.孙晓红；刘源发,广谱性杀虫剂三唑磷的合成研究.西北大学学报：自然科学版 1996,26,(003),219-223.
7.李华；刘毅锋；张娟；王翠玲；张雄,乙氧甲叉基氨基甲酸酯类的合成研究.精细化工 2003,20,(007),440-442.
8.宣日成；史成华,吡虫啉的合成方法.农药 1998,37,(010),11-14.
9.程敬丽；魏方林；朱烈；赵金浩；朱国念,N-[3-氰基-1-(2,6-二氯-4-三氟甲基苯基)-1H-吡唑-5-基]菊酰胺类化合物的合成及生物活性.有机化学 2008,28,(004),622-627.
10.张国生,吡唑类,吡咯类杀虫剂的研发进展.农药科学与管理 2004,25,(011),23-26.
11.白雪；周成合；米佳丽,三唑类化合物研究与应用.化学研究与应用 2007,19,(007),721-729.
12. Zhao, P. L.; Liu, C. L.; Huang, W.; Wang, Y. Z.; Yang, G. F., Synthesis and fungicidal evaluation of novel chalcone-based strobilurin analogues. J. Agric. Food Chem 2007,55, (14),5697-5700.
13. Huang, W.; Zhao, P. L.; Liu, C. L.; Chen, Q.; Liu, Z. M.; Yang, G. F., Design, synthesis, and fungicidal activities of new strobilurin derivatives. J. Agric. Food Chew 2007,55, (8),3004-3010.
14.Cheng, J. L.; Zhao, J. H.; Zhu, G. N.; Lin, F. C.,-(4-Chlorophenyl)-3-methyl-N-(5-methylthiazol-2-yl) butanamide; Acta Cryst.2009, E65, o184.
15.陈启辉,新型杀菌剂苯噻菌胺.农药 2004,43,(011),515-517.
16.野国中；范志金；李正名；李永红；高发旺；王素华,新磺酰脲类化合物的合成及生物活性.高等学校化学学报 2003,24,(009),1599-1603.
17.刘长令,三唑并嘧啶磺酰胺类除草剂的创制经纬.农药 2002,41,(008),45-46.
18.王辉；陈琼,三唑并嘧啶-2-磺酰胺类除草剂的研究进展.华中师范大学学报：自然科学版 2003,37,(001),68-74.
19.刘长令,嘧啶氧(硫)苯甲酸类除草剂的创制经纬.农药 2002,41,(009),44-45.
20.张一宾,由甲氧丙烯酸酯类抗生素开发农用杀菌剂.农药译丛 1995,17,(003),25-29.
21.柏亚罗,Strobilurins类杀菌剂研究开发进展.农药 2007,46,(005),289-295.
22.陈万义；王龙根；李钟华,新农药的研发-方法.进展.化学工业出版社：2007.
23.张一宾；张怿,世界农药新进展.化学工业出版社：2007.
24.杨吉春；吴峤；刘若霖；马士纯；刘长令,杀菌剂开发的新进展.农药 2008,47,(006),402-405.
25.李海屏,杀菌剂新品种开发进展及发展趋势.江苏化工 2004,32,(006),7-12.
26.汪汉成；祁之秋；王建新；陈长军；周明国,肟菌酯对9种植物病原真菌室内活性测定.农药2006,45,(011),780-781.
27. Brase, S.; Encinas, A.; Keck, J.; Nising, C. F., Chemistry and biology of mycotoxins and related fungal metabolites. Chemical Reviews 2009.,109, (9),3903-3990..
28. Strobel, G. A.; Miller, R. V.; Martinez-Miller, C.; Condron, M. M.; Teplow, D. B.; Hess, W. M., Cryptocandin, a potent antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina. Microbiology 1999,145, (8),1919.
29. Li, J. Y.; Strobel, G.; Harper, J.; Lobkovsky, E.; Clardy, J., Cryptocin, a potent tetramic acid antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina. Org. Lett 2000,2, (6), 767-770.
30. Strobel, G. A.; Dirkse, E.; Sears, J.; Markworth, C., Volatile antimicrobials from Muscodor albus, a .novel endophytic fungus. Microbiology 2001,147, (11),2943.
31. Vicente, M. F.; Cabello, A.; Platas, G.; Basilio, A.; Diez, M. T.; Dreikorn, S.; Giacobbe.R. A.; Onishi, J. C.; Meinz, M.; Kurtz, M. B., Antimicrobial activity of ergokonin A from Trichoderma longibrachiatum. Journal of Applied Microbiology 2001,91, (5),806-813.
32. Wagenaar, M. M.; Clardy, J., Dicerandrols, new antibiotic and cytotoxic dimers produced by the fungus Phomopsis longicolla isolated from an endangered mint. J. Nat.Prod 2001,64, (8), 1006-1009.
33. Li, J. Y.; Harper, J. K.; Grant, D. M.; Tombe, B. O.; Bashyal, B.; Hess, W. M.; Strobel, G. A., Ambuic acid, a highly functionalized cyclohexenone with antifungal activity from Pestalotiopsis spp. and Monochaetia sp. Phytochemistry 2001,56, (5),463-468.
34. Tan, R. X.; Zou, W. X., Endophytes:a rich source of functional metabolites. Natural product reports 2001,18, (4),448-459.
35.李桂玲；王建锋,几种药用植物内生真菌抗真菌活性的初步研究.微生物学通报 2001,28,(006),64-68.
36.兰琪；姬志勤；顾爱国；师宝君；吴文君,苦皮藤内生真菌中杀虫杀菌活性物质的初步研究.西北农林科技大学学报 2004,32,(010),79-84.
37.吴萍茹；马旭闽；方金瑞,车前草内生真菌w-90次级代谢产物的研究.海峡药学 2005,17,(006),116-119.
38.曾松荣；徐倩雯；叶保童；柯野；方白玉；黄晓敏,虎杖内生真菌的分离及产抗菌活性物质的筛选.菌物研究 2005,3,(002),24-26.
39.Rotter, B. A., Invited Review:TOXICOLOGY OF DEOXYNIVALENOL (VOMITOXIN). Journal of Toxicology and Environmental Health 1996,48,(1),1-34.
40. Ueno, Y.,Mode of action of trichothecenes.1977,31,885.
41. DeLoach, J. R.; Gyongyossy-Issa, M.; Khachatourians, G. G., Species-specific hemolysis of erythrocytes by T-2 toxin* 1. Toxicology and Applied Pharmacology 1989,97, (1),107-112.
42. Bra Se, S.; Encinas, A.; Keck, J.; Nising, C. F., Chemistry and biology of mycotoxins and related fungal metabolites. Chem. Rev 2009,109, (9),3903-3990.
43. Ueno, Y., Trichothecenes:chemical, biological and toxicological aspects. Elsevier:1983.
44. Anderson, D. W.; Black, R. M.; Lee, C. G.; Pottage, C.; Rickard, R. L.; Sandford, M. S.; Webber, T. D.; Williams, N. E., Structure-activity studies of trichothecenes:Cytotoxicity of analogues and reaction products derived from T-2 toxin and neosolaniol. Journal of Medicinal Chemistry 1989,32, (3),555-562.
45. Schoerital, R., Trichothecenes, zearalenone, and other carcinogenic metabolites of Fusarium and related microfungi. Advances in cancer research 1985,45,217-290.
46. Freeman, G. G.; Morrison, R. I., The isolation and chemical properties of trichothecin, an antifungal substance from Trichothecium roseum Link. Biochemical journal 1949,44, (1),1.
47. Godtfredsen, W. O.; Grove, J. F.; Tamm, C., Zur Nomenklatur einer neueren Klasse von Sesquiterpenen. Helvetica Chimica Acta 1967,50, (6),1666-1668.
48. Johannisson, A.; Bj Rkhag, B.; Hansson. W.; Gadhasson, I. L.; Thuvander, A., Effects of four trichothecene mycotoxins on activation marker expression and cell proliferation of human lymphocytes in culture. Cell biology and toxicology 1999,15, (4),203-215.
49. Zhou, H. R.; Harkema, J. R.; Hotchkiss, J. A.; Yan, D.; Roth, R. A.; Pestka, J. J., Lipopolysaccharide and the trichothecene vomitoxin (deoxynivalenol) synergistically induce apoptosis in murine lymphoid organs. Toxicological Sciences 2000,53, (2),253.
50. Isaka, M.; Punya, J.; Lertwerawat, Y.; Tanticharoen, M.; Thebtaranonth, Y., Antimalarial activity of macrocyclic trichothecenes isolated from the fungus Myrothecium verrucaria. J. Nat. Prod 1999,62, (2),329-331.
51. Garcia, C. C.; Rosso, M. L.; Bertoni, M. D.; Maier, M. S.; Damonte, E. B., Evaluation of the.antiviral activity against Junin virus of macrocyclic trichothecenes produced by the hypocrealean epibiont of Baccharis coridifolia. Planta medica 2002,68, (3),209-212.
52. Ueno, Y.; Hsieh, D., The toxicology of mycotoxins. CRC Critical Reviews in Toxicology 1985,14, (2),99-132.
53. Tamm, C.; Jeker, N., Synthesis of macrocyclic trichothecene mycotoxins. Tetrahedron 1989,45, (8), 2385-2415.
54. Mohr, P.; Tori, M.; Grossen, P.; Herold, P.; Tamm, C., Synthesis of verrucarin A and 3a-hydroxyverrucarin A from verrucarol and diacetoxyscripenol (anguidine). Helv. Chim. Acta 1982, 65,(1412),707.
55. Corley, D. G.; Rottinghaus, G.E.; Tempesta, M. S., Novel trichothecenes from. Tetrahedron Letters 1986,27, (4),427-430.
56. Ziegler, F. E.; Nangia, A.; Schulte, G., Synthesis of the 1,3-dioxolane ring system of the trichothecenes sambucinol and sporol via a stereoselective Claisen rearrangement. Journal of the American Chemical Society 1987,109,(13),3987-3991.
57. Ziegler,F.. F.; Nangia Michael, S., Sporol:A structure revision. Tetrahedron Letters 1988,29, (14), 1665-1668.
58. Ziegler, F. E.; Nangia Gayle, A., The synthesis of neosporol:A trichothecene in search of a natural product. Tetrahedron Letters 1988,29, (14),1669-1672.
59. Ziegler, F. E.; Metcalf III, C. A.; Schulte, G., Confirmation by total synthesis of the revised structure of sporol:an application of cyclic thionocarbonate-initiated radical cyclization. Tetrahedron Letters 1992,33,(22),3117-3120.
60. Ziegler, F. E.; Metcalf III, C. A.; Nangia, A.; Schulte, G., Structure and total synthesis of sporol and neosporol. Journal of the American Chemical Society 1993,115, (7),2581-2589.
61. Ziegler, F. E.; Sobolov, S. B., Synthesis of a highly functionalized carbon ring skeleton for the trichothecene anguidine. Journal of the American Chemical Society 1990,112, (7),2749-2758.
62. Brian, P. W.; Dawkins, A. W.; Grove, J. F.; Hemming, A. G.; Lowe, D., J. Exp. Bot.1961,12,1.
63. Sigg, H. P.; Mauli, R.; E., F.; Hauser, D.,J. Chem. Soc, Chem. Commun.1965,,26.
64. Dawkins, A. W., J. Chem. Soc, Chem. Commun.1965,,27.
65. Colvin, E. W.; Cameron, S., Partial syntheses of the trichothecene mycotoxins, calonectrin and deoxynivaienol. Tetrahedron Letters 1988,29, (4),493-496.
66. Jeker, N.; Mohr, P.; Tamm, C., Conversion of anguidine into calonectrin and 3-deacetyl-calonectrin. Tetrahedron Letters 1984,25, (49),5637-5640.
67. Tulshian, D. B.; Fraser-Reid, B., The ready conversion of anguidine into verrucarol and trichodermol. Tetrahedron Letters 1980,21, (47),4549-4552.
68. Wani, M.C.; Rector, D. H.; Cook, C. E., Synthesis of HT-2 toxin, neosoianiol, T-2 toxin,3'-hydroxy T-2 toxin, and sporotrichiol from anguidine by routes involving hydroxyl inversion/esterification. The Journal of Organic Chemistry 1987,52, (15),3468-3470.
69. McDougal, P. G.; Schmuff, N. R., In Progress in the Chemistry of Organic Natural Products.1985,47, 153.
70. loos, R.; Belhadj,A.; Menez, M.; Faure, A., The effects of fungicides on Fusarium spp. and Microdochium nivale and their associated trichothecene mycotoxins in French naturally-infected cereal grains. Crop Protection 2005,24, (10),894-902.
71. Colvin, E. W.; Malchenko, S.; Raphael, R. A.; Roberts, J. S., Total synthesis of (±)-trichodermin. Journal of the Chemical Society, Perkin Transactions l 1973,1989-1997.
72. Kraus, G. A.; Roth, B.; Frazier, K.; Shimagaki, M., Stereoselective synthesis of calonectrin. Journal of the American Chemical Society 1982,104, (4),1114-1116.
73. Still, W. C.; Tsai, M., Total synthesis of (±)-trichodermol. Journal of the American Chemical Society 1980,102, (10),3654-3655.
74. O'Brien, M.K.; Pearson, A. J.; Pinkerton, A. A.; Schmidt, W.; Willman, K., A total synthesis of (±)-trichodermol. Journal of the American Chemical Society 19.89,111, (4),1499-1501.
75. Trost, B. M.; McDougal, P. G., Total synthesis of verrucarol. Journal of the American Chemical Society 1982,.104, (22),6110-6112.
76. Schlessinger, R. H.; Nugent, R. A., Total synthesis of racemic verrucarol. Journal of the American Chemical Society 1982,104, (4),1116-1118.
77. Roush, W. R.; D'Ambra, T. E., Total synthesis of (±)-verrucarol. Journal of the American Chemical Society 1983,105, (4),1058-1060.
78. Hua, D. H.; Venkataraman, S.; Chan, R. Y. K.; Paukstelis, J. V., Enantioselective total synthesis of (+)-12,13-epoxytrichothec-9-ene and its antipode. Journal of the American Chemical Society 1988, 110, (14),4741-4748.
79. Fujimoto, Y.; Yokura, S.; Nakamura, T.; Morikawa, T.; Tatsuno, T., Total synthesis of 12,13-epoxytrichothec-9-ene. Tetrahedron Letters 1974,15, (29),2523-2526.
80. Anderson, D. W.; Black, R. M.; Lee, C. G.; Pottage, C.; Rickard, R. L.; Sandford, M. S.; Webber, T. D.; Williams, N. E., Structure-activity studies of trichothecenes:cytotoxicity of analogs and reaction products derived from T-2 toxin and neosolaniol. Journal of medicinal chemistry 1989,32, (3), 555-562.
81. Kaneko, T.; Schmitz, H.; Essery, J. M.; Rose, W.; Howell, H. G.; O'Herron, F. A.; Nachfolger, S.; Huftalen, J.; Bradner, W. T., Structural modifications of anguidin and antitumor activities of its analogs. Journal of Medicinal Chemistry 1982,25, (5),579-589.
82. Adler, S. S.; Lowenbraun, S.; Birch, B., Anguidine:A broad phase Ⅱ study of the Southeastern Cancer Study group. Cancer Treatment Reports 1984,68, (2),423-425.
83. DeSimone, P. A.; Greco, F. A.; Lessner, H. F.; Bartolucci, A., Phase Ⅱ evaluation of anguidine (NSC 141537) in 5-day courses in colorectal adenocarcinoma. A Southeastern Cancer Study Group trial. American Journal of Clinical Oncology:Cancer Clinical Trials 1986,9, (3),187-188.
84. Porcher, J. M.; Dahel, C.; Lafarge-Frayssinet, C.; Chu, F. S.; Frayssinet, C., Uptake and metabolism of T-2 toxin in relation to its cytotoxicity in lymphoid cells. Food and Chemical Toxicology 1988,26, (7),587-593.
85. Porcher, J. M.; Lafarge-Frayssinet, C.; Frayssinet, C.; Nurie, A.; Melcion, D.; Richard-Molard, D., Determination of cytotoxic trichothecenes in corn by cell culture toxicity assay. J Assoc Off Anal Chem 1987,70, (5),844-849.
86. Ueno, Y.; Hsieh, D., The toxicology of mycotoxins. CRC Critical Reviews in Toxicology 1985,14, (2),99-132.
87. Robbana-Barnat, S.; Lafarge-Frayssinet, C.; Frayssinet, C., Use of cell cultures for predicting the biological effects of mycotoxins. Cell Biology and Toxicology 1989,5, (2),217-226.
88. Chanh, T. C.; Hewetson, J. F., Structure/function studies of T-2 mycotoxin with a monoclonal antibody. Immunopharmacology 1991,21, (2),83-90.
89. Ramu, A.; Yagen, B.; Ramu, N., The cytotoxicity of T-2 toxin and related 12,13-epoxytrichothecenes to Adriamycin-sensitive and-resistant P388 leukemia cells. Cancer chemotherapy and pharmacology 1989,24, (4),264-267.
90. Godtfredsen, W. O.; Vangedal, S., Trichodermin, a New Sesquiterpene Antibiotic. ACTA CHEMICA SCANDINAVICA 1965,19,1088-1102.
91. Wei, C.; Vaughan, J. R., Mechanism of Action of the Mycotoxin Trichodermin. Proc. Nat. Acad. Sci. USA:1974,71, (3),713-717.
92. Fonzi, W. A.; Sypherd, P. S., Antimicrob. Agents Chemother.1986,29, (4),570-575.
93. Choi, S, U,; Choi,E. J.; Kim, K.H.; Kim, N. Y.; Kwon, B. M.; Kim, S. U.; Bok, S. H.; Lee, S. Y.; Lee, C. O., Cytotoxicity of trichothecenes to human solid tumor cells in vitro. Archives of Pharmacal Research 1996,19, (1),6-11.
94. Mekhancha Dahel. C.; Lafarge F. C.; Venuat A. M., Trichothecenes as antitumoral substances: inhibiting effect on the growth human lymphocytes, lymphoma and leukaemia cells. J. Cell. Pharmacol.1991,2,343-350.
95. Cutler, H. G.; LeFiles, J. H, Trichodermin:Effects on plants. Plant & Cell Physiol.1978,19, (1), 177-182.
96. Adams, P.M.; Hanson, J. R., Sesquiterpenoid metabolites of Trichoderma polysporum and T. sporulosum. Phytochemistry 1972,11, (1),423.
97. Cutler, H. G.; Cle, P. D.; Arrendale, R. F.; Bassfield, R. L.; Cox, R. H., Dendrostilbella sp.(85-25), a new source of trichodermin. Agricultural and Biological Chemistry 1986,50, (10),2667-2668.
98. Ghisalberti, E.L.; Sivasithamparam, K., Antifungal antibiotics produced by Trichoderma spp. Soil Biology and Biochemistry 1991,23, (11),1011-1020.
99. Bamburg; J. R., Biological and biochemical actions of trichothecene mycotoxins. Progress in molecular and subcellular biology 1983,8,41-110.
100. Altomare, C.; Norvell, W. A.; Bjorkman, T.; Harman, G. E., Solubilization of phosphates and micronutrients by the plant-growth-promoting and biocontrol fungus Trichoderma harzianum Rifai 1295-22. Applied and Environmental Microbiology 1999,65, (7),2926-2933.
101. Wiley, Trichoderma-Application, mode of action and potential as a biocontrol agent of soilborne plant pathogenic fungi. Innovative Approaches to Plant Disease Control 1987,,137-160.
102. Papavizas, G. C.; Lewis, J. A., Effect of Gliocladium and Trichoderma on damping-off and blight of snapbean caused by Sclerotium rolfsii in the greenhouse. Plant Pathology 1989,38, (2),277-286.
103. Knaflewski, M.; Ka U Ewicz, A.; Zaworska, A., Charakterystyka u ytkowa i morfologiczna nowych odmian szparaga lekarskiego (Asparagus officinalis L.)[Economic and morphological features of new asparagus (Asparagus officinalis L.) cultivars]. Zeszyty Problemowe Post pow Nauk Rolniczych (Advances of Agricultural Sciences Problem Issues) 497:311-317. In Polish:2004.
104. Pristchepa, L.; Voitka, D.; Kasperovich, E.; Stepanova, N., Influence of Trichodermin-BL on the decrease of fiber flax infection by diseases and the improvement of its production quality. Journal of Plant Protection Research 2006,46, (1),1.
105. Apsite, A.; Svinka, J.;Strikauska, S.; Viesturs,U.; Lisovska, A.; Bicevskis, E.; Svoka,l., The use of trichodermin for plant protection. Proceedings of Agricultural Science 1989,9,114-118.
106. Apsite, A,; Strikauska, S.; Svinka, J.; Vanags, J.; Viesturs, U.; Bicevskis, J.; Lisovska, A. Method for trichodermin production. No.5360,1991.
107. Lewis, J. A.; Papavizas, G. C., Biocontrol of cotton damping-off caused by Rhizoctonia solani in the field with formulations of Trichoderma spp. and Gliocladium virens. Crop Protection 1991,10, (5), 396-402.
108. Apsite, A.; Viesturs, U.; Steinberga, V.; Toma, M., Morphology and antifungal action of the genus Trichoderma cultivated in geometrically dissimilar bioreactors. World Journal of Microbiology and Biotechnology 1998,14, (1),23-29.
109. Apsite, A,;Viesturs, U.; Berzina, G.; Shteinberga, V., Production of the biofungicide trichodermin preparation and its effect upon barley crop.1996.
110. Prischepa, L.; Voitka, D.; Feklistova,I.; Maximova, N., Bioproducts in the control of soil-borne pathogens under cover.1992.
111. Zafari, D.; Koushki, M.:M.; Bazgir, E., Biocontrol evaluation of wheat take-all disease by Trichoderma screened isolates. African Journal of Biotechnology 2008,7, (20),3653-3659.
112.茆振川；侯桂凤,木霉菌对侵染苹果枝条的轮纹病菌的抑制作用.落叶果树 1996,28,(003),6-7.
113.赵蕾,木霉菌的生物防治作用及其应用.生态农业研究 1999,7,(001),66-68.
114.杨依军；齐中波,拮抗木霉菌在生物防治中的作用.天津农业科学 2000,6,(003),29-33.
115.王革；李梅云,木霉菌对烟草黑胫病菌的拮抗机制及其生物防治研究.云南大学学报：自然科学版 2001,23,(003),222-226.
116.高克祥；郭润芳,木霉菌对五种植物病原真菌的重寄生作用.山东农业大学学报：自然科学版 2002,33,(001),37-42.
117.吴石平；燕嗣皇,施肥及栽培方法对木霉菌在辣椒上的促生增产效应的影响.贵州农业科学2002,30,(004),13-15.
118.邵红涛；许艳丽；李春杰；李兆林,筛选用于防治大豆尖孢镰刀菌根腐病的木霉菌株.中国油料作物学报 2004,26,(004),74-77.
119.黄艳青；庄敬华；高增贵；徐韶；陈捷：木霉菌诱导甜瓜抗枯萎病相关防御反应酶系的研究.沈阳农业大学学报 2005,36,(005),546-549.
120.庄敬华；陈捷；杨长成；高增贵；刘限；牟连晓；郑雅楠,生防木霉菌生物安全性评价.中国农业科学 2006,39,(004),715-720.
121.于新；田淑慧；徐文兴；刘开启,木霉菌生防作用的生化机制研究进展.中山大学学报：自然科学版 2005,44(002),86-90.
122.俞晓平；陈列忠；申屠旭萍,植物内生菌及其代谢物在生物农药创制中的应用.浙江农业学报2006,18,(005),289-293.
123.石一珺；申屠旭萍；俞晓平,木霉菌素产生菌的诱变育种.安徽农业科学 2008,36,(029),12806-12807.
1.24.石一珺；申屠旭萍；俞晓平,1株枸骨内生真菌菌株的分类鉴定及其代谢产物的生防作用研究.植物病理学报 2009,,(004),362-367.
125.章初龙；徐同,木霉属组和Pachybasium组的分子系统学研究.菌物系统 2002,21,(4),538-546.
126.章初龙；徐同,Trichoderma harzianum及其近缘种的分子系统学研究.生物多样性 2003,11,(001),10-19.
127.章初龙；徐同,我国河北,浙江,云南及西藏木霉种记述.菌物学报 2005,24,(002),184-192.
128.章初龙；王国平；郑必强；陈绍瑗；林福呈,紫杉木霉ZJUF0986抗真菌活性代谢产物分离提取及其活性研究.菌物学报 2008,27,(003),439-446.
129.王国平；鲁书玲；郑必强；章初龙,紫杉木霉ZJUF0986代谢产物及其对番茄灰霉病的抑制作用.浙江农业学报 2008,20,(002),104-108.
130. Zhang, C. L.; Liu, S.; Lin, F. C.; Kubicek, C. P.; Druzhinina, I. S., Trichoderma taxi sp. nov., an endophytic fungus from Chinese yew Taxus mairei. FEMS microbiology letters 2007,270, (1),90-96.
131.林福呈；章初龙；陈绍瑗,一种紫杉木霉菌株及其在制备木霉菌酯素中的用途.CN101113414,2007.
132. Shao-Yuan, C.; Chu-Long, Z.; Yu-Zhe, C.; Fu-Cheng, L., Trichodermin (4β-acetoxy-12,13-epoxytrichothec-9-ene). Acta. Cryst. E 2008, E64, o702.
133.袁志林；陈益存；章初龙；林福呈；陈连庆,中国木霉属内生真菌一个新记录种Trichoderma chlorosporum.菌物学报 2008,27,4.
134.王国平；郑必强；章初龙；林福呈,木霉菌酯素的提纯方法.CN101168758,2007.
135.王国平；郑必强；章初龙；林福呈,发酵生产木霉菌酯素的方法及所用的发酵培养基.CN101168757,2007.
136. Tanford, C., How protein chemists learned about the hydrophobic factor. Protein Science 1997,6, (6), 1358-1366.
137. Montal, M.; Mueller, P., Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties. Proceedings of the National Academy of Sciences of the United States of America 1972,69, (12),3561.
138. Dill, K. A., Dominant forces in protein folding. Biochemistry 1990,29, (31),7133-7155.
139. Kubinyi, H.; Folkers, G.; Martin, Y. C.,3D QSAR in drug design:Recent advances. Springer Netherlands:1998.
140. Kubinyi, H., QSAR and 3D QSAR in drug design Part 1:methodology. Drug Discovery Today 1997, 2, (11),457-467.
141. Wold, S.; Johansson, E.; Cocchi, M.,3D QSAR in drug design:theory, methods and applications. PLS-Partial Least Squares Projection to Latent Structures. ESCOM, Lieden 1993,,523-550.
142. Cramer, R. D.; DePriest, S. A.; Patterson, D. E.; Hecht, P., In 3D QSAR in drug design:Theory, Methods, and Applications. Leiden:ESCOM 1993,443,485.
143.苏笠；杨劲；王友群；王广基,化合物脂水分配系数计算软件及比较研究.中国药科大学学报2008,39,(002),178-182.
144.王连生,分子结构性质与活性.化学工业出版社：1997.
145. Lodge, K. B., Octanol-Water Partition Coefficients of Cyclic C-7 Hydrocarbons and Selected Derivatives. J. Chem. Eng. Data 1999,44, (6),1321-1324.
146. Edelbach, D. J.; Lodge, K. B., Insights into the measurement of the octanol-water partition coefficient from experiments with acrylate esters. Physical Chemistry Chemical Physics 2000,2, (8),1763-1771.
147. Finizio, A.; Vighi, M.; Sandroni, D., Determination of n-octanol/water partition coefficient (Kow) of pesticide critical review and comparison of methods. Chemosphere 1997,34, (1),131-161.
148.Eadsforth, C. V.; Moser, P., Assessment of reverse-phase chromatographic methods for determining partition coefficients. Chemosphere 1983,12, (11-12),1459-1475.
149.陈凯先；蒋华良；嵇汝运,计算机辅助药物设计—原理,方法药及应用.上海：上海科技出版社：2001.
150.(?)黄青春,杀菌剂作用机制的最新研究进展.世界农药 2006,28,(001),10-15.
151.刘斌；(?)飞；姚建华；廖泉；范波涛；杀菌剂,除草剂和杀虫剂的先导筛选规则.农药学学报(?)(003),220-228.
152.张礼和,从生物有机化学到化学生物学.化学进展 2004,16,(002),313-318.
153.沈旭；蒋华良；余长缨；陈莉莉,小分子与蛋白质靶分子相互作用研究方法及应用.化学生物学进展，化学工业出版社：2005；498-529.
154 I (?)ey, D., Molecular recognition of DNA structure by proteins that mediate genetic recombination. Journal of Molecular Recognition 1994,7, (2),71-78.
155. (?). S. S.; Mayo, M. W.; Bruno, J. G.; Bronk, B. V.; Batt, C. A.; Chambers, J. P., A review of molecular recognition technologies for detection of biological threat agents. Biosensors and Bioelectronics 2000,15, (11-12),549-578.
156. Vogel, V.; Thomas, W. E.; Craig, D. W.; Krammer, A.; Baneyx, G., Structural insights into the mechanical regulation of molecular recognition sites. Trends in biotechnology 2001,19, (10), 416-423.
157.吴会灵；杨原；张重杰；何锡文,小分子与核酸相互作用的研究进展.分析化学(FENXI HUAXUE) 2004,32.
158.李锐；任海平；孙艳亭；姚英艳；卢奎,小分子与生物大分子间非共价相互作用分析方法研究进展.分析化学 2006,6,(12).
159. Vajda, S.; Camacho, C. J., Protein-protein docking:is the glass half-full or half-empty. TRENDS in Biotechnology 2004,22, (3),110-116.
160. Smith, G. R.; Sternberg, M. J. E., Prediction of protein-protein interactions by docking methods. Current Opinion in Structural Biology 2002,12, (1),28-35.
161. Smith, G. R.; Sternberg, M. J. E.; Bates, P. A., The Relationship between the Flexibility of Proteins and their Conformational States on Forming Protein-Protein Complexes with an Application to Protein-Protein Docking. Journal of Molecular Biology 2005,347, (5),1077-1101.
162. Abagyan, R.; Totrov, M., High-throughput docking for lead generation. Current Opinion in Chemical Biology 2001,5, (4),375-382.
163.田青.二噁英类环境毒素及其抑制剂的分子对接和定量构效关系研究.同济大学,2008.
164. Lengauer, T.; Rarey, M., Computational methods for biomolecular docking. Current opinion in structural biology 1996,6, (3),402-406.
165.梁赤周.抗三唑磷基因工程抗体的研制及同源建模.浙江大学,2010.
166.刘飞；黄青春,杀菌剂作用机制的最新研究进展.世界农药 2006,28,(001),10-15.
167.思彬彬；杨卓,甲氧基丙烯酸酯类杀菌剂作用机理研究进展.世界农药 2007,29,(006),5-9.
168.闫晓静；金淑惠；陈馥衡；王道全,Strobilurin类杀菌剂作用靶标的研究进展.农药学学报 2006,8,(004),299-305.
169.安田康,新杀菌剂的靶标和先导化合物的探索.农药译丛 2000,13,(3),1-1.
170.阎隆飞；孙之荣,蛋白质分子结构.清华大学出版社：1999.
171. De Groot, M. J., Designing better drugs:predicting cytochrome P450 metabolism. Drug discovery today 2006,11,(13-14),601-606.
172. Kelly, S. L.; Lamb, D. C.; Kelly, D. E., Cytochrome P450 biodiversity and biotechnology. Biochemical Society Transactions 2006,34,1159-1160.
173. Lepesheya, G. I.; Waterman,M. R., Sterol 14 [alpha]-demethylase cytochrome P450 (CYP51), a P450 in all biological kingdoms. Biochimica et Biophysica Acta (BBA)-General Subjects 2007,1770, (3),467-477.
174. Waterman, M. R.; Lepesheva, G. I., Sterol 14 [alpha]-demethylase, an abundant and essential mixed-function oxidase. Biochemical and biophysical. research communications 2005,338, (1), 418-422.
175. Fiecchi, A.; Kienle, M. G.; Scala, A.; Galli, G.; Paoletti, E. G.; Cattabeni,F.; Paoletti, R., Hydrogen exchange and double bond formation in cholesterol biosynthesis. Proceedings of the Royal Society of London. Series B, Biological Sciences 1972,180, (1059),147-165.
176. Mitropoulos, K. A.; Gibbons, G.F.; Reeves, B. E. A., Lanosterol 14a-demethylase. similarity of the enzyme system from yeast and rat liver. Steroids 1976,27, (6),821-829.
177. Akhtar, M.;Alexander, K.; Boar, R. B., Chemical and enzymic studies on the characterization of intermediates during the removal of the 14 alpha-methyl group in cholesterol biosynthesis. The use of 32-functionalized lanostane derivatives. Biochem J.1978,169, (3),449-463.
178. Gibbons, F. G.; Pullinger, C. R.; Mitropoulos, K. A., Studies on the mechanism of lanosterol 14 alpha-demethylation. A requirement for two distinct types of mixed-function-oxidase systems. Biochem J.1979,183, (2),309-315.
179. Trzaskos, J. M.; Bowen, W. D.; Shafiee, A.; Fischer, R. T.; Gaylor, J. L., Cytochrome P-450-dependent oxidation of lanosterol in cholesterol biosynthesis. Microsomal electron transport and C-32 demethylation. Journal of Biological Chemistry 1984,259, (21),13402.
180. Yoshida, Y.; Aoyama, Y., Yeast cytochrome P-450 catalyzing lanosterol 14 alpha-demethylation. I. Purification and spectral properties. Journal of Biological Chemistry 1984,259, (3).1655.
181. Kalb, V. F.; Loper, J. C.; Dey, C. R.; Woods, C. W.; Sutter, T. R., Isolation of a cytochrome P-450 structural gene from Saccharomyces cerevisiae. Gene 1986,45, (3),237-245.
182. Nebert, D. W.; Nelson, D. R.; Coon, M. J.; Estabrook, R. W., The P450 superfamily:update on new sequences, gene mapping, and recommended nomenclature. DNA and Cell Biology 1991,10, (1), 1-14.
183. Aoyama, Y.; Horiuchi, T.; Gotoh,O.; Noshiro, M.; Yoshida, Y., CYP51-like gene of Mycobacterium tuberculosis actually encodes a P450 similar to eukaryotic CYP51. Journal of biochemistry 1998,124, (4),694-696.
184. Trzaskos, J.; Kawata, S.; Gaylor, J. L., Microsomal enzymes of cholesterol biosynthesis. Purification of lanosterol 14 alpha-methyl demethylase cytochrome P-450 from hepatic microsomes. Journal of Biological Chemistry 1986,261, (31),14651.
185. Kahn, R. A.; Bak, S.; Olsen, C. E., Isolation and reconstitution of the heme-thiolate protein obtusifoliol 14 alpha-demethylase from Sorghrum bicolor. JBiol. Chem.1996,271, (51), 32944-32950.
186. Bellamine, A.; Mangla, A. T.; Nes, W. D., Characterization and catalytic properties of the sterol 14 alpha-demethylase from Mycobacterium tuberculosis actually encodes a p450 similar to eukaryotic cyp51. Proc Natl Acad Sci USA 1999,96, (16),8937-8942.
187. Ji, H.; Zhang, W.; Zhou, Y.; Zhang, M.; Zhu, J.; Song, Y.; Lu, J.; Zhu, J., A Three-Dimensional Model of Lanosterol 14 [alpha]-Demethylase of Candida albicans and Its Interaction with Azole Antifungals. J. Med. Chem 2000,43, (13),2493-2505.
188. Kelly, S.; Lamb, D.; Cannieux, M.; Greetham, D.; Jackson, C.; Marczylo, T.; Ugochukwu, C.; Kelly, D., An old activity in the cytochrome P450 superfamily (CYP51) and a new story of drugs and resistance. Biochemical Society Transactions 2001,29,122-128.
189. Lepesheva, G. I.; Waterman, M. R., CYP51--the omnipotent P450. Molecular and cellular endocrinology 2004,215, (1-2),165-170.
190.杨娇艳；杨劭,稻瘟病菌(Magnaporthe grisea)14α-去甲基化酶与抑制剂的结合特性与新型杀真菌剂筛选.2008,1-10.
191. Aoyama, Y., Recent progress in the CYP51 research focusing on its unique evolutionary and functional characteristics as a diversozyme P450. Front. Biosci 2005,10,1546-1557.
192. Nelson, D. R., Cytochrome P450 and the individuality of species. Archives of Biochemistry and Biophysics 1999,369, (1),1-10.
193. Lepesheva, G. L.; Virus, C.; Waterman, M. R., Conservation in the CYP51 Family. Role of the B Helix/BC Loop and Helices F and G in Enzymatic Function. Biochemistry 2003,42, (30),9091-9101.
194. Holtje, H, D.; Fattorusso, C., Construction of a model of the Candida albicans lanosterol 14-[alpha]-demethylase active site using the homology modelling technique. Pharmaceutica Acta Helvetiae 1998,72, (5),271-277.
195. Poulos, T. L.; Finzel, B. C.; Howard, A. J., High-resolution crystal structure of cytochrome P450cam 1. Journal of molecular biology 1987,195, (3),687-700.
196. Hasemann, C. A.; Ravichandran, K. G.; Peterson, J. A.; Deisenhofer, J., Crystal structure and refinement of cytochrome P450terp at 2.3 A resolution* 1. Journal of molecular biology 1994,236, (4),1169-1185.
197. Cupp-Vickery, J. R.; Poulos, T. L., Structure of cytochrome P450 eryF involved in erythromycin biosynthesis. Nature Structural & Molecular Biology 1995,2, (2),144-153.
198. Ravichandran, K. G.;Boddupalli, S. S.; Hasermann, C. A.; Peterson, J. A.; Deisenhofer, J., Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's. Science 1993, 261,(5122),731-736.
199. Ruge, E.; Korting, H. C.; Borelli, C., Current state of three-dimensional characterisation of antifungal targets and its use for molecular modelling in drug design. International journal of antimicrobial agents 2005,26, (6),427-441.
200.徐铮；曹永兵,麦角甾醇生物合成途径中的抗真菌药作用靶酶.国外医药：抗生素分册 2001,22,(005),193-197.
201. Tuck, S. F.; Patel, H.; Safi, E.; Robinson, C. H., Lanosterol 14 alpha-demethylase (P45014DM): effects of P45014DM inhibitors on sterol biosynthesis downstream of lanosterol. Journal of lipid research 1991, 32, (6),893.
202.王国平；郑必强；章初龙；林福呈木霉菌素测定方法及用途.CN101144808,2007.
203. Shima, J.; Takase, S.; Takahashi, Y.; Iwai, Y.; Fujimoto, H.; Yamazaki, M.; Ochi, K., Novel detoxification of the trichothecene mycotoxin deoxynivalenol by a soil bacterium isolated by enrichment culture. Applied and environmental microbiology 1997,63, (10),3825.
204. Choi, S. U.; Choi, E. J.; Kim, K. H.; Kim, N. Y.; Kwon, B. M.; Kim, S. U.; Bok, S. H.; Lee, S. Y.; Lee, C.O., Cytotoxicity of trichothecenes to human solid tumor cells in vitro. Archives of Pharmacal Research 1996,19, (1),6-11.
205. Anderson, D. W.; Black, R. M.; Lee, C. G.; Pottage,C.; Rickard, R. L.; Sandford, M. S.; Webber, T. D.; Williams, N. E., Structure-activity studies of trichothecenes:cytotoxicity of analogs and reaction products derived from T-2 toxin and neosolaniol. Journal of medicinal chemistry 1989,32, (3), 555-562.
206. Bamburg, J. R., Biological and biochemical actions of trichothecenes mycotoxins. In Progress in molecular and subcellular biology 8, Springer Verlag,:Berlin,1983; 41-110.
207. Mekhancha-Dahel, C.; Lafarge-Frayssinet, C.; Venuat, A. M.; Rosenfeld, C.; Frayssinet, C., Trichothecenes as antitumoral substances:inhibiting effect on the growth human lymphocytes, lymphoma and leukaemia cells. J. Cell. PharmacoL 1991,2,343-350.
208. Melmed, R. N.; Ishai-Michaeli, R.; Yagen, B., Differential inhibition by T-2 toxin of total protein, DNA and isoprenoid synthesis in the culture macrophage cell line J774. Biochemical pharmacology 1985,34, (15),2809-2812.
209. Rosenstein, Y.; Lafarge-Frayssinet, C., Inhibitory effect of Fusarium T-2 toxin on lymphoid DNA and protein synthesis. Toxicol. Appl. Pharmacol.1983,70,283-288.
210. Uenoy Y.; Nakajima, M.; Sakai, K.; Ishii, K.; Sato, N.; Shimada, N., Inhibition of protein synthesis in animal cells. J. Biochem.1973,74,285-296.
211. Cheng, J. L.; Zhou, Y.; Zhao, J. H.; Zhang, C. L.; Lin, F. C., Synthesis and antifungal activity of trichodermin derivatives. Chinese Chemical Letters 2010,21, (09),1037-1040.
212. Fonzi, W. A.; Sypherd, P. S., Trichodermin esterase activity and trichodermin resistance in Mucor racemosus. Antimicrobial agents and chemotherapy 1986,29, (4),570-575.
213.Lucas, H. J.; Schlatter, M. J.; Jones, R. C., The Isomeric 2,3-Epoxypentanes and 2-Pentenes. The Extent to which Mixtures of Diastereomers Are Formed in Reactions of Some Pentane Compounds. Journal of the American Chemical Society 1941,63, (1),22-28.
214. Gelbard, G.; Brunelet, T.; Jouitteau, C., Oxydation d'alcools par l'anhydride chromique dans les conditions du transfert de phase solide-liquide. Tetrahedron Letters 1980,21, (48),4653-4654.
215. Cheng, J. L.; Zhou, Y,; Lin, F. C.; Zhao, J. H.; Zhu, G. N., Trichodermol (4\a-hydroxy-12,13-epoxytrichothec-9-ene). Acta. Cryst. E 2009,65, (o2897).
216. Zhang, C.; Liu, S.; Lin, F.; Kubicek, C. P.; Druzhinina, I. S., Trichoderma taxi sp. nov., an endophytic fungus from Chinese yew Taxus mairei. FEMS microbiology letters 2007,270, (1),90-96.
217. Fr Patent 1,508,066 (Written In French),1968.
218.李述文,范如霖.实用有机化学手册 上海：上海科学技术出版社 1981,12,210.
219. Kaneko, T.; Schmitz, H.; Essery, J. M.; Rose, W.; Howell, H. G.; O'Herron, F. A.; Nachfolger, S.; Huftalen, J.; Bradner, W. T., Structural modifications of anguidin and antitumor activities of its analogs. Journal of Medicinal Chemistry 1982,25, (5),579-589.
220. Choi, S. U.; Choi,E. J.; Kim, K. H.; Kim, N. Y.;Kwon, B. M.; Kim, S. U.; Bok, S. H.; Lee, S. Y.; Lee, C. O., Cytotoxicity of trichothecenes to human solid tumor cells in vitro. Archives of Pharmacal Research 1996,19, (1),6-11.
221. PROCESS-AUTO, A., Processing Package for Imaging Plate Diffractometer. Rigaku Corporation, Tokyo 1998,,.
222. May, J. J.;.Kessler, N.; Marahiel, M. A.; Stubbs, M. T., Crystal structure of DhbE, an archetype for aryl acid activating domains of modular nonribosomal peptide synthetases. Proceedings of the National Academy of Sciences of the United States of America 2002,99, (19),12120.
223. Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A., Completion and refinement of crystal structures with SIR92. Journal of Applied Crystallography 1993,26, (3),343-350.
224. Sheldrick, G. M., A short history of SHELX. Acta Crystallographica Section A:Foundations of Crystallography 2007,64, (1),112-122.
225.Farrugia, L.J., ORTEP-3 for Windows-a version of ORTEP-Ⅲ with a Graphical User Interface (GUI). Journal of Applied Crystallography 1997,30, (5),565.
226. Watkin, D. J.; Prout, C. K.; Carruthers, J. R.; Betteridge, P. W., CRYSTALS. Issue 10. Chemical Crystallography Laboratory. In Oxford, England:1996.
227. Spek, A. L., Structure validation in chemical crystallography. Acta Crystallographica Section D: Biological Crystallography 2009,65, (2),148-155.
228. Clough, J. M.; Godfrey, C.; Hudson, D. H.; Miyamoto, J., Fungicidal Activity:Chemical and Biological Approaches to Plant Protection. In John Wiley & Sons, Ltd Chichester, UK:1998; 109-148.
229. Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P. J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews 1997,23, (1-3),3-25.
230. Clark, D. E.; Pickett, S. D., Computational methods for the prediction of[] drug-likeness'. Drug Discovery Today 2000,5, (2),49-58.
231. Tice, C. M., Selecting the right compounds for screening:does Lipinski's Rule of 5 for pharmaceuticals apply to agrochemicals?. Pest management science 2001,57, (1),3-16.
232. Tice, C. M., Selecting the right compounds for screening:use of surface-area parameters. Pest management science 2002,58, (3),219-233.
233.刘斌；俞飞；姚建华；廖泉；范波涛,杀菌剂,除草剂和杀虫剂的先导筛选规则.农药学学报2007,9,(003),220-228.
234. Zheng, X.; Li, Z.; Wang, Y.; Chen, W.; Huang, Q.; Liu, C.; Song, G., Syntheses and insecticidal activities of novel 2,5-disubstituted 1,3,4-oxadiazoles. Journal of Fluorine Chemistry 2003,123, (2), 163-169.
235. Janicka, M.; O Cik-Mendyk, B.; Tarasiuk, B., Planar chromatography in studies of the hydrophobic properties of some new herbicides. JPC-Journal of Planar Chromatography-Modern TLC 2004,17, (3),186-191.
236. http://www.vcclab.org.
237. http://www.acdlabs.com.
238. Zhao, J. H.; Zhou, Y.; Zhang, J. G.; Cheng, J. L.; Lin, F. C., Dihalogenated Trichodermin (4-\β-Acetoxy-9,10-dibromo-12,13-epoxytrichothec). Acta Cryst.E 2010,66, o210.
239. Plattbe, R. D.; Al-Hetti, M. B.; Weisleder, D.; Sinclair, J. B., A New Trichothecene from Trichothecium roseum. J. Chem. Research (M) 1988,,2461-2473.
240.张红；陈夕军；童蕴慧；纪兆林；徐敬友,纹枯病菌胞壁降解酶对水稻组织和细胞的破坏作用.扬州大学学报：农业与生命科学版 2005,26,(004),83-86.
241.孟庆忠；刘志恒,水稻纹枯病研究进展.沈阳农业大学学报 2001,32,(005),376-381.
242.张穗；肖培英；温广月；曹黎明,氟铃脲对水稻纹枯病菌的毒力和作用机制.植物保护学报 2007,34,(001),87-90.
243.赵丽静；杨晓楠；李祥英；刘峰,11种杀菌剂对水稻纹枯病菌的毒力比较.农药研究与应用2009,,(005),27-29.
244. Ahn, Y. M.; Vander Velde, D. G.; Georg, G.l., Synthetic Studies with 13-Deoxybaccatin Ⅲ. J. Org. Chem 2002,67, (20),7140-7143.
245. Wani, M. C.; Rector, D. H.; Cook, C. E., Synthesis of HT-2 toxin, neosolaniol, T-2 toxin,3'-hydroxy T-2 toxin, and sporotr-ichiol from anguidine by routes involving hydroxyl inversion/esterification. The Journal of Organic Chemistry 1987,52, (15),3468-3470.
246. Stephenson, L. M.; Speth, D. R., Mechanism of allylic hydroxylation by selenium dioxide. The Journal of Organic Chemistry 1979,44, (25),4683-4689.
247. Davidse, L. C., Benzimidazole fungicides:mechanism of action and biological impact. Annual review of phytopathology 1986,24, (1),43-65.
248.潘以楼；汪智渊,油菜菌核病菌对多菌灵的抗药性.中国油料 1997,19,(003),67-68.
249.张夕林；张治；张建明；张谷丰；孙雪梅,多菌灵防治油菜菌核病药效下降原因及综防对策.农药科学与管理 1998,67,(3),15-17.
250.方中达,植病研究方法：第三版.北京：中国农业出版社：1996.
251.裴华；凌忠专,辽宁丹东地区稻瘟病菌生理研究.植物病理学报 1986,16,(4),197-203.
252. Baker, B.; Zambryski, P.; Staskawicz, B.; Dinesh-Kumar, S. P., Signaling in plant-microbe interactions. Science 1997,276,(5313),726-733.
253.周光召；中国科协学术年会,面向21世纪的科技进步与社会经济发展.中国科学技术出版社：1999.
254.孙漱沅；孙国昌,我国稻瘟病研究的现状和展望.植保技术与推广 1996,16,(003),39-40.
255. Kraus, G. A.; Thomas, P. J., Synthesis of 7,7,8-trideuteriated trichothecenes. The Journal of Organic Chemistry 1988,53, (7),1395-1397.
256. Yun, S. Y.; Zheng, J. C.; Lee, D., Stereoelectronic Effect for the Selectivity in C-H Insertion of Alkylidene Carbenes and Its Application to the Synthesis of Platensimycin. Journal of the American Chemical Society 2009,131, (24),8413-8415.
257. Curley Jr, R. W.; Ticoras, C. J., Stereospecific synthesis of the important retinoid synthon ethyl trans-3-formyl-2-butenoate via direct two-stage oxidation of ethyl 3-methyl-2-butenoate. The Journal of Organic Chemistry 1986,51, (2),256-258.
258.谭亚军；李少南；吴小毛,几种杀虫剂对大型蚤的慢性毒性.农药学学报 2004,6,(003),62-66.
259.沈国兴；严国安,农药对藻类的生态毒理学研究：Ⅱ.毒性机理及其富集和降解.环境科学进展1999,7,(006),131-140.
260. Trachtenberg, E. N.; Carver, J. R., Stereochemistry of selenium dioxide oxidation of cyclohexenyl systems. The Journal of Organic Chemistry 1970,35, (5),1646-1653.
261. Brown, H. C.; Dhokte, U. P., Hydroboration.90. Synthesis of 2-Isobutyl-and 2-Isopropylapopinenes. Rates and Stoichiometry of the Hydroboration of 2-Organylapopinenes with Borane-Methyl Sulfide and Borane-Tetrahydrofuran. The Journal of Organic Chemistry 1994,59, (8),2025-2032.
262. Fattorusso, E.; Romano, A.; Taglialatela-Scafati, O.; Irace, C.; Maffettone, C.; Bavestrello, G.; Cerrano, C., Oxygenated cembranoids of the decaryiol type from the Indonesian soft coral Lobophytum sp. Tetrahedron 2009,65, (15),2898-2904.
263. Jones, T. K.; Chu, L.; Mrozik, H.; Slayton, L.; Rafalko, B.; Goldmann, M. L.; Shoop, W. L. Margiatto, G.; Fisher, M. H., Synthesis and biological activity of 4a,4"-disubstituted avermectins. Journal of Agricultural and Food Chemistry 1994,42, (8),1786-1790.
264. Huffman, J. W.; Bushell, S. M.; Miller, J.; Wiley, J. L.; Martin, B. R.,1-Methoxy-, 1-deoxy-11-hydroxy-and 11-Hydroxy-l-methoxy-[Delta] 8-tetrahydrocannabinols:new selective ligands for the CB2 receptor. Bioorganic & medicinal chemistry 2002,10, (12),4119-4129.
265.林琳；叶正和；高同春,水稻稻曲病菌药剂室内生物测定和筛选.安徽农业科学 2008,36,(004),1482-1483.
266.蔡祝南；吴蔚文；高君川,水稻病虫害防治[M1.北京：金盾出版社：1997.
267.缪巧明；李化瑶,云南省稻曲病研究进展.云南农业科技 1994,3,8-10.
268.王疏；周永力,稻曲病菌的病原学.植物病理学报 1998,28,(001),19-24.
269. Goodsell, D. S.; Olson, A. J., Automated docking of substrates to proteins by simulated annealing. Proteins:Structure, Function, and Bioinformatics 1990,8, (3),195-202.
270. Morris, G. M.; Goodsell, D. S.; Halliday, R. S.; Huey, R.; Hart, W. E.; Belew, R. K.; Olson, A. J., Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of Computational Chemistry 1998,19, (14),1639-1662.
271. Diego, S., Affinity user guide. MSI Inc.:USA,2002.
272. Marti-Renom, M. A.; Stuart, A.; Fiser, A., S nchez, R., Melo, F. and Sali, A.(2000) Comparative protein structure modeling of genes and genomes. Annu. Rev. Biophys. Biomol. Struct 29,291-325.
273. Sali, A.; Blundell, T. L., Comparative protein modelling by satisfaction of spatial restraints. Protein Structure by Distance Analysis 1994,,64-86.
274. Fiser, A.; Do, R.; Ali, A., Modeling of loops in protein structures. PRS 2000,9, (09),1753-1773.
275. Laskowski, R. A.; MacArthur, M. W.; Moss, D. S.; Thornton, J. M., PROCHECK:a program to check the stereochemical quality of protein structures. Journal of Applied Crystallography 1993,26, (2),283-291.
276. Pearson, W. R.; Lipman, D. J., Improved tools for biological sequence comparison. Proceedings of the National Academy of Sciences 1988,85, (8),2444.
277. Ito, A.; Sudo, K.; Kumazawa, S.; Kikuchi, M.; Chuman, H. In Three-Dimensional Modeling of Cytochrome P450 14α-Demethylase (CYP51) and Interaction ofAzole Fungicide Metconazole with CYP51,2005; ACS Publications:2005; 142-150.