Green chemistry oriented synthesis of biologically active natural products and structure-activity relationships

本课题以“绿色化学”为目标，取得了如下成果：1.为了发现新的具有生物活性的天然产物，我们采用反相高效液相色谱法和水溶剂系统对高等植物（唇形科、马桑科、茜草科和罗汉果科）中的化学成分进行了研究。研究结果表明，从该植物中分离得到了一些新的倍半萜和二萜化合物.一些细胞毒性类似物是从香茶菜、Perovskia abrotanoides、马桑、Tricalysia dubia和雷公藤中分离的天然产物中合成的。讨论了对映贝壳杉烯型、羟乙基癸烷型和松香烷型天然产物及其半合成类似物的结构与细胞毒活性之间的构效关系。以“绿色化学”为目标，将微波炉用于半合成类似物的制备.采用TL脂肪酶对仲醇进行动力学拆分，得到光学纯的仲醇。其中一种仲醇在半大规模中转化为哌嗪酸。目前我们正在尝试合成一种天然的六肽GE3，它包含了两种哌嗪酸的对映体。发展了钯催化合成重要药物分子骨架吡咯和吲哚的简便方法.以Garner醛为手性池合成了非蛋白质氨基酸。

The results in this project aimed at 'Green Chemistry' are as follows :1. To discover new biologically active natural products, we explored chemical constituents from higher plants (Labiatae, Coriaceae, Rubiaceae, and Podocarpaceae) using HPLC attached with reversed phase column and aqueous solvent systems. As a results, Some new sesqui-and diterpenes were isolated.2. Some cytotoxic analogues were synthesized from natural products, isolated from Rabdosia excisa, Perovskia abrotanoides, Coriaria japonica, Tricalysia dubia, and Tripterygium wilfordii. The structure-activity relationships (SAR) between the structures of ent-kaurene type, isetexane type, and abietane type natural products and their semisynthetic analogues and cytotoxic activity were discussed. The microwave oven was used for preparation of semisynthetic analogues aimed at 'Green Chemistry'.3. The kinetic resolution of secondary alcohols with lipase TL were carried out to produce optically pure secondary alcohols. One of the secondary alcohols was converted to piperazic acids in semi-large scale. Now we are trying to synthesize a natural hexadepsipeptide GE3, which includes both enatiomers of piperazic acids.4. The facile palladium-catalyzed synthesis of pyrroles and indoles, which are important medicinal molecule skeletons, was developed.5. The nonproteogenic amino acids were synthesized from Garner aldehydes as a chiral pool.