松节油基新型生物活性化合物的合成及构效关系研究

Novel N-aminoethyl-terpinene-maleimide was prepared via isomerization of α-pinene, addition of the isomeric product with maleic anhydride, and reaction of the adduct with ethylenediamine using α-pinene, the main component of turpentine, as starting material. Then, five types of novel turpentine-based bioactive compounds, i.e. N-aminoethyl-terpinene-maleimide-based amides, N-aminoethyl- terpinene-maleimide-based Schiff bases, N-aminoethyl-terpinene-maleimide-based thioureas, N-aminoethyl-terpinene-maleimide-based sulfamides, and N-aminoethyl- terpinene-maleimide-based imidazoles, will be designed and synthesized by using the substructure connection method and chemical modification reactions of the amino group in N-aminoethyl-terpinene-maleimide, for realizing optimization and superposition of the active constituents. The synthetic conditions will be investigated, the structures of the products will be characterized, the bioactive activities including antimicrobial, insecticidal, herbicidal, plant growth regulating, antiviral, and interaction with DNA activities will be tested, and the substituent group-bioactivity relationship will be studied. This research project aims at finding novel leading compounds with bioative activities, providing fundamental data for the preparation of new medicine or pesticide, and openning a new pathway for the modification and high-value utilization of turpentine which is a natural and preponderant resource of China.

以松节油的主要成分α-蒎烯为原料，通过α-蒎烯异构再与马来酸酐加成，继而与乙二胺反应制备未见文献报道的N-氨乙基萜品烯马来酰亚胺，然后采用亚结构连接法，通过N-氨乙基萜品烯马来酰亚胺氨基的改性反应，设计和合成N-氨乙基萜品烯马来酰亚胺基酰胺衍生物、N-氨乙基萜品烯马来酰亚胺基席夫碱衍生物、N-氨乙基萜品烯马来酰亚胺基硫脲衍生物、N-氨乙基萜品烯马来酰亚胺基磺酰胺衍生物和N-氨乙基萜品烯马来酰亚胺基咪唑衍生物等五类未见文献报道的松节油基生物活性化合物，实现活性成分的优化叠加。探索合成条件，表征产物结构，测试生物活性(如抗菌、杀虫、除草、植物生长调节、抗病毒、与DNA相互作用等)，研究取代基结构与生物活性的关系，以期寻求具有生物活性的新的先导物质，为创制新的医药或农药打下基础，为我国天然优势资源松节油的改性和高值化利用提供新的途径。

松节油是我国的天然可再生优势资源。松节油的深加工利用是值得深入研究的课题。作为松节油主要成分的α-蒎烯本身具有一定的生物活性，通过α-蒎烯分子的结构改造可以合成多种生物活性物质。本项目开展松节油基新型生物活性化合物的合成及构效关系研究。分别以源自松节油主成分α-蒎烯的N-氨乙基萜品烯马来酰亚胺、N-羧甲基萜品烯马来酰亚胺、蒎酸、α-龙脑烯醛、樟脑酸和樟脑为起始物，通过对其官能团的进一步改性，设计并合成了N-氨乙基萜品烯马来酰亚胺基硫脲、N-氨乙基萜品烯马来酰亚胺基酰胺、N-氨乙基萜品烯马来酰亚胺基磺酰胺、N-氨乙基萜品烯马来酰亚胺基咪唑、α-蒎烯基苯基噻二唑、α-蒎烯基双噻二唑、2-取代酰氨基-5-(α-龙脑烯醛基)-1,3,4-噻二唑、N-［p-(取代氨基磺酰基)苯基］-α-龙脑烯酸酰胺、α-龙脑烯醛基噻二唑-膦酸酯、樟脑酸基酰腙、樟脑酸基苯磺酰胺、樟脑酸基硫脲、樟脑酸基双酰肼、N-(4-取代氨基磺酰基)苯基-酮基蒎酸酰胺、樟脑基苯基硫脲和樟脑基苯甲酰胺等16类共166个松节油基新型生物活性化合物。探讨了合成条件，采用FT-IR、1H-NMR、13C-NMR、ESI-MS、UV-vis和元素分析等手段表征了化合物的结构。生物活性测试结果表明，部分化合物具有优良的抑菌和除草活性，并显示一定的构效关系。项目的研究结果为天然产物基农药的合成和筛选提供了实验依据，为我国天然优势资源松节油的深度开发利用提供了新的途经。