Synthesis Of Nitrogen-salidroside Derivatives With Reduced One Carbon In Side Chain And Study Of Their Anti-hypoxic Activities

Objective The injury and apoptosis caused by plateau hypoxia can give rise to a variety of cardiovascular and cerebrovascular diseases.Therefore,it is important to find the drug with high efficiency and low toxicity which can resist to hypoxia.Salidroside which is separated from Rhodiola rosea has good activity against ischemic anoxia.However,salidroside is difficult to synthesis,and its bioavailability is low.Based on our previous study,this paper reports the synthesis of N-glycoside analogues of salidroside with reduced one carbon in side chain,and their pharmacological activity was detected as well to enrich the study on the structure-activity relationship.Content Salidroside was used as leading compound to synthesis various of its N-glycoside analogues with reduced one carbon in side chain.And their pharmacological activity was detected as well to enrich the study on the structure-activity relationship.Methods（1）Benzylamines which were synthesized via Gabriel synthesis with substituted benzaldehydes as raw material reacted with glucose to give the target compound.（2）Acetyl-β-D-glucopyranosyl amine which was synthesized via acetylation,bromination,azide reaction and reductive amination from D-glucose reacted with different substituted benzyl bromides to give the target compound.（3）Schiff base synthesized from acetyl-β-D-glucopyranosyl amine and substituted benzaldehydes was reduced with Na BH（OAc）₃,after which the target compound yield via deacetylaiton.The protection from ischemia and anoxia of target compounds was detected by MTT.Results 19 target compounds were synthesized in total,confirmed by ¹H-NMR and ESI-MS,17 of which have not been reported yet.Protection of Endothelial cell against hypoxia injury showed that 16 compounds show positive effects,10 of which are superior to salidroside.Conclusion N-glycoside analogues of salidroside with reduced one carbon in side chain were kinds of compounds with the activity against ischemic anoxia.The size,the type and the number of the substitute on phenyl have impact on the activity of the target compound,in which 3-or 4-substitutes on phenyl influence greatly on the activity of the compounds,and the steric hindrance on phenyl is important to the activity as well.