Synthesis,characterization And Whitening Activity Of Arbutin Analogues

Arbutin is a kind of natural bioactivity that can be separated from many kinds of bearberry plants,and it shows many biological activities,such as whitening,anti-oxidization,preventing cough,anti-inflammation,protecting liver,etc.Arbutin is an important additive in commercially available whitening skincare products.One side phenolic hydroxyl group of hydroquinone was coupled with glucose by glycosidic bond to get arbutin.The position of phenolic hydroxyl groups and different kinds of glycogen can also change the activities.Thus developing new arbutin analogues with whitening effect has important practical significance.To further study of structure activity relationship of the arbutin analogues,according to the combination principles,Three kinds of hydroquinones with protection of one side phenolic hydroxyl group were directly coupled with galactose,glucose,xylose,arabinose,valine,phenylalanine and proline,removed the protecting groups to get 28 new arbutin analogues.And we evaluated the inhibition of tyrosinase activity of intermediates and final products,in order to get compounds with better whitening activity.There are three parts in this dissertation:Part I:Reviewed the research progress of hydroquinones,arbutin,glycoside and amino acid of their applications in medicine and drugs.Part II:Described the design,synthesis and characterization of arbutin analogues.We synthesized 31 compounds,and 28 of them have not been reported.1.Using p-dihydroxybenzene,m-dihydroxybenzene and o-dihydroxybenzene as starting material.Through the protection of one side phenolic hydroxyl,we get three different key intermediates(p-HQ-2,m-HQ-2 and o-HQ-2).2.The three kinds of the intermediate coupled with bromo-tetraacetyl galactose,glucose,xylose,arabinose,and eleven kinds of arbutin analogues(p-HQ-4a,m-HQ-4a,o-HQ-4a,m-HQ-4b,o-HQ-4b,p-HQ-4c,m-HQ-4c,o-HQ-4c,p-HQ-4d,m-HQ-4d and o-HQ-4d)were obtained.Eleven kinds of target compounds(p-HQ-5a,m-HQ-5a,o-HQ-5a,m-HQ-5b,o-HQ-5b,p-HQ-5c,m-HQ-5c,o-HQ-5c,p-HQ-5d,m-HQ-5d and o-HQ-5d)were gotten by the removal of benzyl group.3.The o-dihydroxybenzene intermediate coupled with valine,phenylalanine and proline which azyl has been protected,and three kinds of amino acids conjugates of o-dihydroxybenzene(o-HQ-3e,o-HQ-3f and o-HQ-3g)were obtained.Three kinds of target compounds(o-HQ-4e,o-HQ-4f and o-HQ-4g)were gotten by the removal of benzyl group.28 new compounds were characterized by IR,¹H NMR,¹³C NMR and HR-MS,etc.Part III:Their in vitro inhibition activities towards tyrosinase were evaluated and the results indicate that p-HQ-5a,o-HQ-5a,p-HQ-4d,m-HQ-4d and m-HQ-5d had significant inhibition to tyrosinase,p-HQ-5d against tyrosinase are obviously better than positive control?-Abutin,namely the whitening effect of hydroquinone coupled with arabinose is the best,and the variation of position of hydroxyl has no influence on its bioactivity of whitening.