两种番石榴属植物的杂萜化学与抗肿瘤活性研究

Meroterpenoids isolated from Psidium guajava (Myrtacea), possessing a characteristic 3,5-diformylbenzyl phloroglucinol structural unit, are a recently discovered type of natural antitumor agents, which have attracted the interest of chemists due to their unique structures and potent bioactivity. During the course of our investigation on chemical constituents of the leaves of P. guajava collected from Vietnam, five novel sesquiterpenoid-based meroterpenoids with antitumor activity were isolated. Meanwhile, the biomimetic synthesis of a humulene-based meroterpenoid was accomplished by a domino three-component coupling reaction. Plants of the genus Psidium comprise approximately 150 species, among which only two species, P. cattleyanum and P. guajava, are commonly cultivated in China. In this project, we are going to explore the antitumor constituents of the two domestic species and search for more structurally interesting meroterpenoids, on the basis of which, the structure-activity relationship study and biomimetic synthesis of these compounds can be carried out. This research will provide theoretical support for finding a new class of plant-derived antitumor agents.

含有3,5-二甲酰基苄基间苯三酚特征结构单元的混源杂萜，是从桃金娘科植物番石榴叶中新发现的一类罕见结构。这种特征结构单元能够与萜烯、黄酮杂合形成多种抗肿瘤活性显著的新奇骨架，是一类具有极高“创造系数”的植物次生代谢产物。该类杂萜抗癌活性显著，但分离难度大，获得量少，目前尚未有较系统的研究报道。本项目拟对国内分布的番石榴属植物进行系统深入的化学与生物活性研究，以期发现抗肿瘤活性显著的杂萜类先导结构，并在提出合理生源假说的基础上，通过“萜烯-二甲酰基间苯三酚-苯甲醛”三分子偶联反应对各类杂萜骨架进行仿生合成，以拓展天然杂萜的获取来源。这项研究将建立起一套从番石榴属植物中分离、鉴定、合成和活性评价新药源物质的研究方法，为创制具有自主知识产权的抗肿瘤新药提供科学依据。

含有3,5-二甲酰基苄基间苯三酚特征结构单元的混源杂萜，是从桃金娘科植物番石榴叶和果中发现的一类罕见结构。这种特征结构单元能够与萜烯、黄酮杂合形成多种抗肿瘤活性显著的新奇骨架，是一类具有极高“创造系数”的植物次生代谢产物。本项目对国内分布的两种番石榴属植物进行系统的化学成分研究，分离得到化合物单体43个，其中新天然产物结构1个，对特征性杂萜进行抗肿瘤活性评价，发现了2个具有显著抗肿瘤活性的杂萜化合物。同时，对前人报道的ɑ-葡萄糖苷酶抑制剂 (R)-2-ethylhexyl 2H-1,2,3-triazole-4-carboxylate进行了结构修正。另外，项目拓展性地对番石榴杂萜进行了抗病原真菌和11β-羟化类固醇脱氢酶（11β-HSD）抑制活性评价，并对草莓番石榴内生真菌的化学成分进行了初步探索。结合项目前期开展的番石榴杂萜仿生合成研究，形成了一套从该植物资源中分离、鉴定、合成和活性评价新药源物质的研究方法，为创制具有自主知识产权的抗肿瘤新药提供了科学依据。