Study On The Acid Catalytic Conversion Products Of Secoiridoid Gentiopicroside

The diversity of natural products' structure have a great significance for searching biologically active compounds and researching new drugs,but its complex structure is becoming more difficult to collect novel compounds.In order to take advantage of specificity of natural product structure,the novel concept of diversity-enhanced extraction has been proposed,which aims at remodeling molecular scaffolds in natural product extracts by chemical methods and subsequent isolating of each compound,therefore,natural product-like compounds of novel structures produced from such reactions.Gentopicroside is a secoiridoid compound extracted from Gentiana macrophylla Pall,with the pharmacological activity of hepatoprotective,antibacterial and anti-inflammation.It has great valuable for research.Since the gentopicroside has an active hemiacetal structure and a plurality of chiral centers that is easily decomposed and transformed,it can be used as raw material to obtain novel structural with biological activity.In summary,this project applied chemical method of acid-catalyzed in gentiopicroside conversion,on the one hand,to provide more possibilities for finding biologically active compounds with novel structures;on the other hand,to accelerate the conversion of gentiopicroside by acid,confirming the existence of transformation products,providing reference for the quality control of gentiopicroside in the future.In the current work,we focused on the acid catalytic conversion products of gentiopicroside by repeatedly different kinds of column chromatography and semi-preparation high performance liquid chromatography and by the application of NMR,HR-ESI-MS spectroscopy detection technology,about this research 8 compounds were identified,3-Methoxy-1-methyl-hexahydro-cyclopenta[c]pyran-5-one(1,2),4-Hydroxyindan-1-one(5),Erythrocentaurin(6),Swerimilegenin G(3,4),Swerimilegenins E(7),?-D-glucofuranosyl-?-D-glucofuranosyl(8).Among them,compounds 1 and 2 are novel compounds,while compounds 3 to 8 are known structures.In addition,the conversion pathway of the partial conversion products was reversed.At the same time,gentiopicroside was used as a positive control,and macrophages(RAW264.7)induced by lipopolysaccharide(LPS)were used as anti-inflammatory models,to study whether the gentiopicroside conversion products inhibits the inflammatory mediator NO produced by LPS-induced macrophages.Experimental results showed that some gentiopicroside conversion products have anti-inflammatory potential.According to the pharmacopoeia stability test guidelines combined with experimental needs,long-term experiments and accelerated experiments of gentiopicroside were explored.The changes of appearance,color,and content of gentiopicroside were investigated.UPLC-Q-TOF/MS was used to monitor the presence of transformants which were compared with the gentiopicroside-catalyzed product.On the one hand,the generation and change trend of the degradation products of gentiopicroside in the long-term test and accelerated test were verified;on the other hand,it provided preliminary data for the long-term storage of the sample,the selection and preparation of the dosage form,and the determination of the shelf life of the sample.