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

1.为了发现新的生物活性天然产物，我们采用反相色谱柱和水相溶剂系统相结合的高效液相色谱联用技术，对高等植物(唇形科、椰科、茜草科和罗汉果科)的化学成分进行了研究。结果分离得到一些新的倍半萜和二萜类化合物。从香茶菜、香茶菜、马桑、毛滴虫、雷公藤中分离得到的天然产物合成了一些细胞毒类似物。讨论了对位高岭烯型、异己烷型和松香烷型天然产物及其半合成类似物结构与细胞毒活性之间的构效关系。利用微波炉制备了以“绿色化学”为目标的半合成类似物。利用脂肪酶TL对仲醇进行动力学拆分，得到光学纯的仲醇。其中一种仲醇被半大规模转化为哌嗪酸。现在，我们正在尝试合成一种天然的六肽GE3，它包括两种哌嗪酸的对映体。开发了钯催化合成重要的药物分子骨架--吡咯和吲哚的简便方法。以加纳醛为手性池合成了非蛋白生成氨基酸。

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.