Synthesis Of Salidroside Analogues With A Carbon Reduce On Side Chain And Preliminary Study Of Their Anti-hypoxic And Antioxidant Activities

Objective Cardiovascular induced by high altitude hypoxia not only is the threat on the health of plateau region staff, but also directly affect the work efficiency of the people,who habitate in a low altitude area, on the plateau, the completion of the task quality. In recent years, many references reported the high altitude inducing hypoxia resist effects of Rhodiola capsules, which prove promising. Salidroside is the main active ingredient of Rhodiola, with chemical name of hydroxyl ethyl benzene-β-beta D-pyranoid glycosidase (p-2-hydroxyphenethyl-beta D-glucoside), and a Glycoside molecule with a therapy effects on cardiovascular and cerebrovascular diseases, which has the pharmacokinetic shortcomings of fast metabolism, unstable and poor oral availability. In this thesis, with salidroside as the leading molecule, the synthesis of a series of representative salidroside analogues is for the aim of finding the compound with similar or better pharmacological activity in comparison with the leading compound, and with simple synthesis route.Content With salidroside as the leading compound, a series of different substituents and glycosylation salidroside analogues, with a carbon reduce on side chain were designed and synthesized. Then the anti-hypoxia and antioxidant activity of these compounds were tested, and a preliminary structure-activity relationship of salidroside analogue with a carbon reduce on side chain was discussed.Methods With different substitute derivatives of benzaldehyde as the raw materials, a series of different types of the salidroside analogues were synthesized through sodium borohydride reduction, acetyl-glucoside, deacetylation, glycosidation.①After the reduction of substituted benzaldehydes, the products reacted with bromo acetyl sugars (glucose, galactose, xylose). Then a series of sugar oxygen glycoside analogues were systhsized.②the products of several step reactions with substituted benzaldehyde as the starting materials, reacted with2,3,4,6-tetra-O-acetyl-beta-D-1-thio-glucopyranose. A series of sugar glucosinolate analogues were systhsized..③the reduction products of substituted benzaldehyde reacted with2.3.4,6-tetra-O-acetyl-β-D-glucopyranosyl amine. As a result, a series of N-glycoside analogues was systhsized. Anti-hypoxia activities of synthsized compounds on hypoxic injured EA hy926endothelial cells were tested with MTT method. And the antioxidant activities of one part of these compounds were tested with DPPH method.Results47target compounds were synthesized, in which there are33sugar oxygen glycoside analogues,10sugar glucosinolate analogues, and4N-glycoside analogues. In them,35compounds have not been reported by previous document, which were confirmed by1H NMR and ESI-MS. The result of activity test showed that2-(3,4-methylenedioxy-phenyl)methyl-1-amino-beta-D-glucosidase (N04) has better anti-hypoxic activity than salidroside, and twelve salidroside analogues with a carbon reduce on side chain have free radical scavenge activity of some degree, moreover some of the compounds shows good antioxidant activity.Conclusion Part of the compounds synthesized have protective effects on hypoxia endothelial cell, and are available through relative simple synthesis route. The preliminary SAS results shows:the location of the substituent and their character, the type of glycosidic, the type of bond of aglycone have some relationship with the activities. The introduction of nitrogen glycoside bond could enhance the pharmacological activity of the compounds. And it is possible, in salidroside analogues with a carbon reduce on side chain, to find some compounds with higher activity than salidroside, through the rational change of substitute on benzene ring, type of glycosyl and glucosidic bond.