Study On The Construction Of 2-deoxy And 2,3-unsaturated Glycosides

Carbohydrates,which are ubiquitously distributed throughout the three domains of life,play significant roles in a variety of vital biological processes.In addition,in bioactive drugs with sugar motifs,the glycosyl moiety may contribute to the better bioavailabilities of those drugs and the switch of the mechanism of drug action in some cases.Deoxysaccharides are often found to occur frequently as a structural fragment in glycoconjugates in a single or multiple units.Researchers have been attracted to the stereoselective construction of the 2-deoxyglycosides due to their challenging and stability.The focus in this field has been on developing new glycosylation reactions that permit the mild and selective construction of deoxyglycosides.In this thesis,two major topics have been discussed:(1)the construction of 2,3-dideoxyglycoside;(2)the construction of 2-deoxyglycoside.2,3-Unsaturated glycosides are excellent chiral synthetic intermediates for initiating diversity-directed synthesis,enabling the successful creation of a library of stereochemically pure compounds with unique structures and complexities.2,3-Deoxysugars are important building blocks in many bioactive molecules such as antibiotics.The acid-catalyzed allylic rearrangement of glycals in presence of alcohols,known as Ferrier rearrangement,is widely employed to obtain 2,3-unsaturated glycosides.The catalysts that can promote the Fischer reaction can be basically divided into autocatalytic systems,protonic acid catalysts(TFA,CSA,etc.),Lewis acid catalysts(InCl3,Fe(OTf)3,etc.),heteropolyacid catalysts(Montmorillonite K-10,etc.)as well as some single electron transfer reagents(DDQ,TCNE,etc.).In this thesis,we have developed a method to install the 2,3-unsaturated glycosidic linkages via a protonic acid-catalyzed Ferrier rearrangement.In this method,treatment of glycal with bulky silyl groups such as TBDPS with different alcohol acceptors results in the formation of the desired 2,3-unsaturated glycosides with high stereoselectivity in the presence(±)-CSA at 85? or CF3SO3H at rt.We successfully synthesized 10 kinds of 2,3-unsaturated glycoside derivatives by using those reaction conditions,and carried out data evidence and structural analysis.2-Deoxyglycosides are also an important member of saccharides.2-Deoxysugars are important structural frames found in many bioactive natural products and drug molecules,such as the anthracycline antibiotic daunorubicin,the anticancer drug doxorubicin and so on.Currently,sugar chemistry scientists have designed a variety of methods for the synthesis of 2-deoxyglycosides,which could be divided into the following five categories:1).Direct synthesis(including glycosyl halides,thioglycosides,and activated oxygen leaving groups);2).Indirect approaches;3).Glycal addition;4).De novo synthesis;5).The anomeric alkylation approach.These synthetic methods have certain advantages to construct 2-deoxyglycosides,but also have some shortcomings.In this work,we have developed a method to stereoselective construction of 2-deoxyglycosides using 2,2-dimethylbut-3-ynylthio-2-deoxyglycosides as donors.Firstly,five different 2,2-dimethylbut-3-ynylthio-2-deoxyglycosyl donors have been successfully prepared;Secondly,we have investigated the in-situ generation of glycosyl iodides using the above-mentioned thioglycosides as substrates in the presence of iodine.And then the optimization of glycosylation of the glycosyl iodides with alcohol acceptors has been conducted.Finally,the substrate scopes of the glycosylation have been explored under the optimized condition.Different glycosyl acceptors and non-sugar acceptors could be coupled with thioglycosides to provide the desired 2-deoxyglycosides in good yield with high stereoselectivity.