Highly Selective Glycosylations Based on Phosphorus-containing Leaving Groups

含碳水化合物的生物分子中糖基含量的生物学意义的增加引起了人们对立体控制糖苷反应的合理设计和实施的极大兴趣。我们在这方面的努力导致了新的糖基供体的开发，这些糖基供体含有二苯基磷酸酯、二苯基膦酰亚胺或硫代二磷酸二酯作为离开基团，其糖苷构成了高度立体控制的1，2-反式-β-和1，2-顺式-α-糖苷键的温和而有效的构建方法。通过对含N，N，N‘，N’-四甲基磷酰胺酸酯的糖基供体的广泛研究，发现含N，N，N‘，N’-四甲基磷酰胺酸酯的糖基供体不仅具有良好的货架稳定性，而且在糖苷化反应中具有明显的优势。三氟化硼乙醚也能活化磷酰胺，形成主要的1，2-反式-β-连接的甾体苷。除了没有邻基参与的糖苷化反应外，苯甲酰基保护的糖基磷酰胺在TMSOTf或三氟化硼的助剂作用下，糖苷化还导致1，2-反式-β-连接的糖苷或二糖的排他性形成。作为上述结果的推广，实现了2-脱氧-α或β-糖苷和2-氨基-2-脱氧-β-糖苷的立体控制合成

An increase in the biological significance of saccharide moieties of carbohydrate-containing biomolecules has generated considerable interest in the rational design and implementation of stereocontrolled glycosidation reactions. Our efforts in this area have led to the development of new glycosyl donors incorporating diphenyl phosphate, diphenylphosphinimidate, or phosphorodiamidimidothioate as leaving groups, the glycosidations of which constitute mild and efficient methods for the highly stereocontrolled construction of 1,2-trans-beta- and 1,2-cis-alpha-glycosidic linkages. After an extensive evaluation of substituents on the phosphorus atom of the leaving groups, we have now found that glycosyl donors incorporating N,N,N',N'-tetramethyl-phosphoroamidates exhibit not only excellent shelf-stabilities but also the following distinct advantages in the glycosidation reactions.TMSOTf-promoted glycosidation of the benzyl-protected glycopyranosyl N,N,N',N'-tetramethyl-phosphoroamidates exhibits the highest 1,2-trans-beta-selectivity known to date. The phosphoroamidates can be also activated by boron trifluoride etherate to result in the predominant formation of 1,2-trans-beta-linked steroidal glycosides. Apart from the glycosidation without neighboring group participation, glycosidation of benzoyl-protected glycopyranosyl phosphoroamidates led to the exclusive formation of 1,2-trans-beta-linked glycosides or disaccharides with the aid of TMSOTf or boron trifluoride etherate as promoters. As an extension of the above results, stereocontrolled syntheses of 2-deoxy-alpha or beta-glycosides and 2-amino-2-deoxy-beta-glycosides have been achieved