Design of Glycosidation Reactions Directed toward Efficient Synthesis of Biologically Active Oligosaccharide Chains

The快速增长significance of oligosaccharide chains as constituents of biologically importantcompounds such as antitumor antibiotics, glycolipids，glycoproteins has sparked considerable interest in the rational design and development ofstereocontrolled glycosidation reactions directed toward the block synthesis.As part of a program todevelop novel and efficient glycosidation methods capitalizing on the phosphorus-containing leavinggroups,我们现在已经发现glycosyl donors incorporating diethyl phosphite exhibit only excellentshelf-stabilities but the following distinct advantages in the glycosidation reactions. (1)Coupling of benzyl-protected glycopyranosyl diethyl phosphites with a variety of acceptor alcoholsbf_3 oet_2 as a promoter even at -78゚C to exhibit the highest1,2-trans-beta-selectivity known to date for glycosidations with a non-participating group on O-2.TMSOTf-mediated glycosidation of glycosyl phosphites bearing participating groups at C-2constitutes an extremely mild and general method for the stereocontrolled construction of1,2-trans-beta-glycosidic linkages. (3) A direct method for the construction of2-deoxy-beta-glycosidic linkages has also been developed by using 2-deoxyglycopyranosyl diethylphosphites in the presence of a catalytic amount of TMSOTf，wherein glycosidations of 2-deoxy-D-gluco-and 2-deoxy-L-rhamnopyranosyl donors with primary alcoholsbeen found to exhibit the highest beta-selectivity known to date.The phosphoroamidateswhich have proven to be compatible with a variety of protective group interchange conditions，play a pivotal role as the "disarmed" donors in the block synthesis of oligosaccharides based on the block synthesis" armed / disarmed " concept, while the diphenylphosphinimidates, p h o sphorodiamidimidothioates,diethyl phosphites can serve as the "armed" donors。

The rapidly growing significance of oligosaccharide chains as constituents of biologically important compounds such as antitumor antibiotics, glycolipids, and glycoproteins has sparked considerable interest in the rational design and development of stereocontrolled glycosidation reactions directed toward the block synthesis.As part of a program to develop novel and efficient glycosidation methods capitalizing on the phosphorus-containing leaving groups, we have now found that glycosyl donors incorporating diethyl phosphite exhibit not only excellent shelf-stabilities but also the following distinct advantages in the glycosidation reactions. (1) Coupling of benzyl-protected glycopyranosyl diethyl phosphites with a variety of acceptor alcohols can be effected by the aid of BF_3・OEt_2 as a promoter even at -78ﾟC to exhibit the highest 1,2-trans-beta-selectivity known to date for glycosidations with a non-participating group on O-2. (2) TMSOTf-mediated glycosidation of glycosyl phosphites bearing participating groups at C-2 constitutes an extremely mild and general method for the stereocontrolled construction of 1,2-trans-beta-glycosidic linkages. (3) A direct method for the construction of 2-deoxy-beta-glycosidic linkages has also been developed by using 2-deoxyglycopyranosyl diethyl phosphites in the presence of a catalytic amount of TMSOTf, wherein glycosidations of 2-deoxy-D-gluco-and 2-deoxy-L-rhamnopyranosyl donors with primary alcohols have been found to exhibit the highest beta-selectivity known to date.The phosphoroamidates, which have proven to be compatible with a variety of protective group interchange conditions, play a pivotal role as the "disarmed" donors in the block synthesis of oligosaccharides based on the "armed/disarmed" concept, while the diphenylphosphinimidates, phosphorodiamidimidothioates, and diethyl phosphites can serve as the "armed" donors.