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

寡核苷酸链快速增长的显著性作为生物学上重要的化合物的稳定性，如抗微生物、糖脂蛋白和糖蛋白在理性设计和开发中具有明显的可确定性兴趣，如立体可控硅反应被定向到块合成.作为一个程序的一部分，以开发新颖和有效的糖基化方法资本化对磷酸盐含有的离开组，我们现在已经找到了一个糖基捐赠者用于合成二乙基磷酸盐展览，不仅是优秀的货架稳定性，但也是在糖基化反应中遵循的地区优势。（1）与不同受体酒精的BF_3和Oet_2的启动子即使在-78 ° C中发现了最高的1，2-反式Beta-选择性已知与O-2的非参与组的糖基化发生的日期。（2） TMSOTf-mediated 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）2-deoxy-beta-glycosidic链接构造的一种直接方法也已经开发出来，使用2-deoxyglycopyranosyl二ethyl磷酸在TMSOTf的催化剂数量中的存在，其中含有2-deoxy-D-gluco-和2-deoxy-L-rhanosyl捐赠者的一种含有初级酒精的化合物已经找到以显示出已知的最高β-选择性日期。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，phosphorodiamidioates， and 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.