The Stuctural Modifucation Of Picroside Ⅰ、Ⅱ And Study Of Structure-Activity Relationship

Picrorhiza scrophulariiflora is the dry rhizome of Scrophulariaceae Picrorhiza scrophulariiflora Pennell, which has effects of hepatoprotective, anti-inflammatory, anti-tumor. It was demonstrated that iridoid glycosides, in Picrorhiza scrophulariiflora, is the active biological ingredient by pharmacology studies, in which content of Picroside Ⅰ and Picroside Ⅱ is highest, department picrorhizae anti-inflammatory, anti-tumor main active ingredient.After preliminary study found that, PicrosideⅠ、Ⅱ is metabolized quickly after oral administration, a very short half-life, low blood concentration, bioavailability is not high; in order to increase the activity and bioavailability of drugs, by chemical methods PicrosideⅠ、Ⅱ structural modification,attempts to synthesize a series of derived compounds, which having high biological activity and bioavailability.By 95% ethanol extract,extracts by macroporous resin and silica gel column chromatography to give PicrosideⅠ、Ⅱ, by 1H-NMR, 13C-NMR structures were confirmed to PicrosideⅠ、Ⅱ, through structural analysis:PicrosideⅠ、Ⅱ structure having a plurality of hydroxyl groups, the reaction is more active in the site, and therefore the PicrosideⅠ、Ⅱ as the precursor compound, in the DCC catalyzed, Boc-amino acids and dehydration condensation of the hydroxyl in PicrosideⅠ、Ⅱ, directed synthesis of a series of amino acid derivatives, glycine derivative 1, alanine derivative 4, valine derivatives 3 and proline derivatives 8. In addition, by alkylation, halogenation, acylation method modified to give a total of 23 derivatives, by 1H-NMR,13C-NMR, MS, DEPT, HSQC, HMBC spectroscopy and other testing methods to identify the structure of 23 compounds, new compounds which have not been reported 21 compounds, and all of the compounds of 1H-NMR,13C-NMR data for a detailed home.Determination of the 23 derivatives on Hepg-2 human tumor cell proliferation inhibition activity by MTT assay, and summarizes the structure-activity relationship. The results showed that:after the removal of glucose lead compounds reduce the antitumor activity; enhanced activity if (1,10) to form a ring; after the introduction of Boc-amino acids has a strong inhibitory effect for Hepg-2 tumor cells; different substituents strength of anti-tumor activity was in the following order:Boc-Pro>Boc-Val>Boc-Ala; replace the position strength of anti-tumor was in the following order:2’>6’>3’; the increased activity of 3,4 is reduced and 3 bits substituted alkoxy, reduced activity if(3,10) to form a ring.By chemical methods PicrosideⅠ、Ⅱ structural modification,synthesized a series of derivatives having anti-tumor activity, and by biological activity and chemical structure combined,describes the structure-activity relation-ships of PicrosideⅠ、Ⅱ, study of amino acid synthesis with PicrosideⅠ、Ⅱ, a new method iridoid class of structural modification research, to lay the foundation for the development of a higher biological activity of new drugs.