松节油合成新型倍半萜烯基噻唑类、噻二唑类和三唑类化合物及生物活性研究

Turpentine is a renewable natural resource and is one of the special forest products in China. Synthesis of new types of sesquiterpenyl thiazoles, thiadiazoles, triazoles derivatives will be carried out using the main component of turpentine oil longifolene as the starting material. Effects of asymmetric oxidation, Michael addition-cyclization, oxidation-in situ cyclization, and different reaction conditions on the stereoselectivities of the products is examined, and the new synthetic methods of the sesquiterpenyl group-containing heterocyclic compounds will be probed. The relationship between the structures of functional groups and the enantioselectivities of products will be investigated, and the separating and purifying methods of isolongifolenyl heterocyclic compounds will be explored. The structures of the synthesized series of compounds are characterized. The cytotoxicities of the synthesized compounds for tumor cell lines including gastric cancer, lung cancer, Breast cancer, and leukemia will be examined, and further investigation of Anti tumor effect in vivo of the compounds with good antineoplastic activities will be further done. Sesquiterpenyl -containing heterocyclic compounds with strong bioactivity and targeting ability will be found by bioactivity screening in the test platform of in-vitro and in -vivo antitumor activity test. The structure-activity relationship between compound structures and their bioactivities will be explored based on the examination results of the influence of the functional groups structures composed in the compounds on their bioactivities. The target of this project is to synthesize 50-60 new chiral isolongifolenyl heterocyclic compounds, and hope to discover 4-5 new compounds with development prospect. The research results will provide theoretical basis for broadening the new utilization field of turpentine oil, and will give far-reaching significance for increasing the application value of turpentine oil in China.

以我国特色林产资源--松节油为研究对象，合成新型手性倍半萜烯基噻唑类、噻二唑类、及三唑类系列杂环化合物。研究不对称氧化、耦合环化、原位氧化环化及不同反应条件对产物立体选择性的影响，探索倍半萜烯基系列杂环化合物的合成新方法；研究基团结构与对映选择性的关系，对所合成的系列杂环化合物的结构进行表征；探索这些新型化合物的对胃癌、肺癌、乳腺癌、及白血病等肿瘤细胞的细胞毒作用，并对有较好抗肿瘤活性的化合物进行体内抗肿瘤作用的初步研究。通过体外和体内抗肿瘤活性测试平台，对所合成化合物进行活性筛选，寻找具有较强活性和靶向性的异长叶烯基衍生物，研究不同官能团结构对活性的影响，探索化合物结构与生物活性之间的构效关系。通过本项目研究，合成50-60个新型倍半萜烯基系列杂环化合物，力争发现4-5个具有开发前景的新型化合物，为开拓我国松节油的利用新领域提供理论基础，对提高我国松节油的应用价值具有重要意义。

本项目以我国特色林产资源——松节油为研究对象，成功合成了新型的合成了异长叶烯基噻唑腙类化合物、异长叶烷基吡唑类及异长叶烷基-2-氨基嘧啶类化合物、异长叶烷基噻唑啉酮衍生物和异长叶烯基噻唑啉酮衍生物、诺蒎烷基噻唑类和噻唑酮类化合物、诺蒎烷基缩氨基硫脲类化合物和诺蒎烷基噻唑腙类化合物、异莰烷基缩氨基硫脲类衍生物、莰基-2-氨基嘧啶类化合物和3-芳亚甲基莰酮缩氨基硫脲类化合物。研究不对称氧化、耦合环化、原位氧化环化及不同反应条件对产物立体选择性的影响，探索倍半萜烯基系列杂环化合物的合成新方法；研究基团结构与对映选择性的关系、对所合成的系列杂环化合物的结构进行表征；探索了这些新化合物对抗肿瘤、抗炎、抑菌、杀虫等生物活性，研究不同官能团结构对活性的影响，探索了化合物结构与生物活性之间的构效关系。通过研究，成功合成了12类204个新型手性异长叶烯基杂环化合物，从中筛选出12个具有良好应用前景的新化合物。为开拓我国松节油的利用新领域提供了理论基础，对提高我国松节油的应用价值具有重要的意义。