Highly Selective Glycosylations Based on Phosphorus-containing Leaving Groups

含碳水化合物的生物分子的糖部分的生物学意义的增加已经在立体控制的糖苷化反应的合理设计和实施中产生了相当大的兴趣。我们在这一领域的努力已经导致了新的糖基供体的发展，包括磷酸二苯酯，二苯基膦亚胺酯，或磷酰二亚胺硫代作为离去基团，其糖苷化构成温和和有效的方法，高度立体控制的建设1，2-反式-β-和1，2-顺式-α-糖苷键。在对离去基团的磷原子上的取代基进行了广泛的评价之后，我们现在发现掺入N，N，N ′，N ′-四甲基-氨基磷酸酯的糖基供体不仅表现出优异的贮存稳定性，而且在糖苷化反应中表现出以下明显的优点。2-反式-β-选择性。氨基磷酸酯也可以被三氟化硼醚合物活化，导致主要形成1，2-反式-β-连接的甾体糖苷。除了没有相邻基团参与的糖苷化之外，苯甲酰基保护的吡喃葡萄糖基氨基磷酸酯的糖苷化导致在TMSOTf或三氟化硼醚合物作为促进剂的帮助下排他性地形成1，2-反式-β-连接的糖苷或二糖。作为上述结果的延伸，已经实现了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