| Carbohydrates are multifunctional compounds which contain a lot of hydroxyls leading to it is necessary to selective protection of those hydroxyl groups while proceeding organic reaction.To achieve target building blocks with suitable selective protection methods and protecting groups is one of the core problems of oligosaccharide synthesis.Numerous methods were developed to solve the above problems,and among them,organotin-mediated(especially of dibutyltin oxide)regioselective protection has been extensively employed method for many years for its easy to operate and high selectivity.However,its physiological toxicity and environmentally unfriendly hinder the application of organotin-mediated protection.Recently,selective protection methods of carbohydrates based on organotin-catalysis were constructed for green synthesis.And those methods were applied to many kinds of regioselective protection while few researches reported about alkylation.Research on regioslective alkylation has important significance for it could introduce protecting group and modified groups to sugars and its derivatives could be used to acquired building blocks for oligosaccharide synthesis and precursor molecule for organic synthesis.Here the paper attempted to explore and develop the regioselective benzylation strategy on the basis of organotin-catalyzed selective protection for carbohydrates,and then achieved diverse alkylatation.1.Organotin-catalyzed regioselective benzylation of cis-1,2-diols and terminal 1,2-diolsBenzyl group is important hydroxyl protection group in oligosaccharide synthesis,and it is significant to achieve selective benzylation.For the first time,we developed a novel mechanism of organotin and bromide ion catalyzed benzylation.On account of the mechanism,we established regioselective benzylation method of sugars based on catalytic amount of dibutyltin oxide,and applied to a series of sugar derivatives and non-sugar diols.And,dibutyltin dichloride or dimethyltin dichloride is capable of dibutyltin oxide.This method can be used to benzylation of equatorial hydroxy group of cis-1,2-diol and primary hydroxy group of terminal 1,2-diol with high selectivity,and obtained mono-benzylated products which have important significance in building blocks synthesis.2.Dibutyltin dichloride catalyzed regioselective mono-alkylation and multiple-alkylaiton of hydoxy groupsOn account of the succeeding in organotin-catalyzed regioselective benzylation,we achieved allylation and propargylation of a series of sugar derivatives and non-sugar diols.And the propargylated products were used to synthesize triazole disaccharide and trisaccharide by click reaction without pre-protected.Moreover,we introduced long-chain alkyl group to sugar molecules to change their biological or physical property,and obtained surfactant molecules with potential values.Besides,multiple alkylation of sugar substrates was developed,and this contributed to simplified the procedures and enhance the efficiency of oligosaccharide synthesis.3.Dibutyltin dichloride catalyzed regioselective benzylation of trans-1,2-diolsIn previous studies,we developed regioselective benzylation method based on organotin catalysis,and this conditions presented high selectivity to cis-1,2-diols or terminal 1,2-diols.However,this method failed to benzylation of substrates only contain trans-1,2-diol structure.We speculated through analysis,it was hard to formation of stannylene structures between organotin and trans-1,2-diol,together with the high activity of benzyl bromide resulted in substrates reacted with benzyl bromide immediately,which lead to failing in selective protection.In present research,we represented of benzyl bromide with benzyl chloride,and selected partially protected sugar as substrates,then achieved to bezylation a series of trans-1,2-diol substrates based on dibutyltin dichloride catalysis.According to present literature reports,those results showed similar or better selectivity and yield compares to the organotin-mediated methods. |
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