创新药物雷腾舒在雷公藤内酯醇结构上引入一个羟基，保持了原化合物的免疫活性，显著降低了毒性。本项目拟在雷腾舒Ⅰ期临床体内代谢研究的基础上，首先对代谢产物进行合理的化学结构剖析，随后对相关可能代谢产物进行有效的化学合成或微生物合成，并将合成的化合物与临床研究的代谢产物进行比对，最终确定出关键的代谢产物。同时进一步对代谢产物进行类药性质研究，以便寻找具有优良药代性质的第二代候选新药物。阐明不同位点引入羟基对环氧结构代谢的影响，及其与活性或毒性的关系，阐明雷公藤二萜分子中环氧结构代谢反应的特点。

(5R)-Hydroxytriptolide (Leitengshu) is a novel immunosuppressive agent under clinical development. By introduction of the 5-beta-hydroxyl group to the natural drug triptolide, its therapeutic index has greatly improved. The project intended to resonabal spectulate the chemical structure of metabolites of the innovative new drug Leitengshu on the basis of the phaseⅠclinical in vivo metabolic studies, followed by chemical and microbial synthesis of the possible metabolites. And the synthesized compounds will be compared with the clinical metabolites. Finally the key metabolites will be determined. Furthermore, drug-like properties of the metabolites will be studied in order to find the second generation of new candidates with excellent pharmacokinetic properties. The relationship of molecular structure with activity and toxicity of the serial derivatives will be elucidated, especially the epoxide moiety to the metabolism properties will be investigated.