4,7-二氢普伐他汀的分离、结构解析与活性研究

Isolation, structural identification and bioactivity of 4,7-dihydropravastatin

目的研究普伐他汀生产发酵过程中的相关物质。方法采用多种色谱技术进行分离纯化,从普伐他汀发酵液中分离得到化合物(H2PV),进行波谱学和单晶X-射线衍射分析。采用体外模型评价该化合物的抗HMG-CoA还原酶活性。结果经MS,1H-NMR,13C-NMR和单晶X-射线衍射分析,确定H2PV为4,7-二氢普伐他汀,并确定了绝对构型。该化合物无抗HMG-CoA还原酶活性。结论确证了UK标准中将4,7-二氢普伐他汀作为相关物质的科学性。

Objective To study related substances from the fermentation broth of pravastatin, Methods The compound H2PV was isolated and purified by silica gel column and pre-HPLC, and its structure was identified by spectroscopy and single-crystal X-ray diffraction. Its HMG-CoA reducase inhibitory activity was evaluated in vitro. Results The compound H2PV was identified as 4,7-dihydropravastatin by MS, ^1H-NMR, ^13C-NMR and singlecrystal X-ray diffraction. It showed no inhibitory effect on HMG-CoA reducase. Conclusion It is rational to define 4, 7-dihydropravastatin as a related substance ofpravastatin in UK pharmacopoeia.