Construction Of ?-mannopyranosidic Bond Based On 2,6-mannose Lactone And Its Application

?-mannoside as a structural motif can often be found in a wide variety of natural products and those compounds with the ?-mannoside structure play important roles in biological activities in organisms.However,stereoselective construction of?-mannosides is challenging since both the anomeric effect and the steric effect of the C-2 axial substituent on the mannopyranosyl ring favor the formation of ?-mannosides.Studies on stereoselective construction of ?-mannosides have been attracting much attention from synthetic chemists due to their important biological activities and the challenging in construction.In our previous work,we have developed an efficient?-mannosylation method using a 2,6-lactone-bridged thiomannosyl donor via remote acyl group participation as well as O-4 steric effect and demonstrated the easy opening of lactone disaccharides by a catalytic amount of NaOMe or by reduction with LiBH4.For our first generation of ?-mannosylation,stoichiometric promotor is necessary for the glycosylation.Later,preliminary studies on developing a catalytic version of?-mannosylation have been conducted,however,no progress has been made.In this thesis,we plan to do further investigation on the development of our second generation of ?-mannosylation using a 2,6-bridged lactone donor under a catalytic condition.In this thesis,the following main topics have been covered:(1).Gram-scale synthesis of 2,6-bridged lactone donor has been achieved.Compared with our previous method,benzyl group has been installed on C-3 hydroxyl group by using catalytic amount of dibutyltin oxide and the product purification was simplified,which resulted in the efficient benzylation in high yield.It turns out the time for benzylation is critical for the high yield(4 h,yield 83%;literature:48 h,yield 41%).(2).Synthesis of 2,6-bridged lactone donors with an alkyne ester as the leaving group at C-1 position(5-hexynoate and ortho-hexynybezoate).Two donors with an alkyne ester as leaving group were synthesized in five steps according to our reported procedure with slight modification.With the new donors in hand,the glycosylation reaction conditions were investigated and the optimal reaction condition is:2,6-bridged mannosyl lactone was used with ortho-hexynybezoate group at C-1 position as glycosyl donor and 5 mol%of Hg(OTf)2 was used as the promotor.Under the optimal condition,high ?-stereoselectivity was achieved.(3).Three ortho-hexynybezoate donors were synthesized with different acyl protecting groups at C-4 position such as Ac,Boc,Bz and Piv groups.The effects of the C-4 acyl groups on the ?-stereoselectivity were studied and the resulted revealed that the C-4 acyl group plays an important role in the ?-mannopyranosylation by both remote acyl group participation and stericeffect.(4).Substrate scopes of the ?-mannopyranosylation were explored under the optimal glycosylation condition.A series of glycosyl acceptors were used to undergo glycosylation with the ortho-hexynybezoate donor with a pivaloyl group at C-4 position and the corresponding glycosides were obtained with high ?-selectivity in good yields,which demonstrates the broad substrate scopes for this method.(5).Studies on the synthesis of ?-1,2-mannuronates and ?-1,2-mannans using the above-mentioned ?-mannopyranosylation.Owing to the unique structural characteristics of the 2,6-bridiged lactone donor,in which all of the hydroxyl groups have been protected by different groups,a particular hydroxy group on mannosyl sugar ring should be released via orthogonal deprotection under certain specific condition once the ?-mannopyranosylation has been done.Thus,this method could have the high potentials for rapid synthesis of ?-mannuronates and ?-mannans with versatile ?-1,2,?-1,3,?-1,4 and ?-1,6 glycosyl linkages.In this thesis,?-1,2-oligomannuronate and?-1,2-oligomannan were selected as the synthetic target to test the efficiency of this?-mannopyranosylation methodology and the synthetic work is ongoing.In conclusion,we have developed a new strategy for catalytic efficient?-mannopyranosylation.The donor used for the new method could be synthesized in a gram scale in 5 steps.This method has a wide substrate scope for the construction of?-mannosides and then in this work,the application of the method to the synthesis of a trisaccharide in which ?-(1-2)linkages is the basis to form ?-1,2-oligomannuronate and ?-1,2-mannsoyl oligosaccharide.Considering the unique structural features of the 2,6-bridged mannosyl lactone,we will synthesize other ?-linked oligomannurarates and mannosyl oligosaccharides,for example,?-1,4-mannose oligosaccharide and?-1,4-oligomannuronate,in the future.