西罗莫司新类似物FIM-R140的分离和结构鉴定

Isolation and identification of sirolimus analogue FIM-R140

目的从西罗莫司产生菌吸水链霉菌FC904发酵液的粗提物中分离纯化未知杂质FIM-R140,鉴定其化学结构。方法采用硅胶柱层析和制备液相分离纯化获得FIM-R140,进行理化性质以及IR、UV、NMR和HRMS等波谱分析,鉴定该杂质的化学结构。用SRB测定化合物体外抗肿瘤活性,用沙氏液体培养基二倍稀释法测定化合物的抗真菌活性。结果与结论纯化获得HPLC纯度为97.05%的FIM-R140,结构鉴定为31-差向雷帕霉素,为首次报道的西罗莫司同分异构体。FIM-R140的抗肿瘤活性较西罗莫司略低,对白念珠菌的抑菌作用弱于西罗莫司。

Objective To isolate and identify FIM-R140,a metabolite from the broth of the sirolimus producing strain Streptomyces hygroscopicus FC904.Methods FIM-R140 was separated and purified by silica gel chromatography and preparative liquid chromatography.Its chemical structure was determined by physicochemical properties and spectral analysis including IR,UV,NMR,and HRMS.The anti-cancer activity of FIM-R140 was determined by the SRB method in vitro,and the antifungal activity was evaluated by the serial two-fold broth dilution method.Results and Conclusion FIM-R140 with HPLC of 97.05%was obtained,and it was identified as 31-epi-rapamycin,a sirolimus isomer,which was reported for the first time.The anti-cancer activity and anti-fungus activity of FIM-R140 were slightly weaker than those of sirolimus.