Highly Selective Glycosylations Based on Phosphorus-containing Leaving Groups

基于含磷离去基团的高选择性糖基化

• 批准号: 03671013
• 负责人: HASHIMOTO Shun-ichi
• 金额: $ 1.28万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03671013/
• 关键词: Phophorus-containing leaving groups; Glycosylation; 1,2-trans-Glycoside; 1,2-trans-Mannoside; 2-Deoxyglycoside; Bis(dimethylamido)phosphate; Diphenylphosphinimidate; Phosphorothioate; 2-デオキシグリコシド; 2ーデオキシグリコシド; アドリアマイシン; ビス(ジメチルアミド)ホスファ-ト; ホスホロ

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

含碳水化合物生物分子的糖部分的生物学意义的增加引起了人们对立体控制糖苷化反应的合理设计和实施的极大兴趣。我们在这一领域的努力导致了新糖基供体的开发，其中包含磷酸二苯酯、二苯膦亚胺酯或硫代磷酸二脒基亚胺酯作为离去基团，其糖苷化构成了高度立体控制的1,2-反式-β-和1,2-顺式-α-糖苷键构建的温和且有效的方法。经过对离去基团磷原子上的取代基的广泛评估，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储存稳定性，而且在糖苷化反应中具有以下明显的优势。TMSOTf 促进的苄基保护的糖苷化 吡喃糖基 N,N,N',N'-四甲基-氨基磷酸酯表现出迄今为止已知的最高的 1,2-反式-β-选择性。氨基磷酸酯也可以被三氟化硼醚化物活化，导致主要形成 1,2-反式-β-连接的甾体糖苷。除了没有邻近基团参与的糖苷化外，苯甲酰保护的吡喃糖基氨基磷酸酯的糖苷化导致在TMSOTf或三氟化硼乙醚作为促进剂的帮助下独家形成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

项目成果

橋本 俊一: "糖鎖工学" 産業調査会, 19 (1992)

桥本俊一：“糖工程”工业研究组，19（1992）

橋本 俊一: "A Mild and Rapid 1,2-Trans-Glycosidation Method via Benzolyl-Protected Glycopyranosyl P,P-Diphenyl-N-(p-Toluenesulfonyl)-phosphinimidates" Heterocycles. 30. 775-778 (1990)

Shunichi Hashimoto：“通过苯甲酰保护的吡喃糖基 P,P-二苯基-N-(对甲苯磺酰基)-次膦酰亚胺酯进行温和快速的 1,2-反式糖苷化方法” 30. 775-778 (1990)。

橋本 俊一: "A Mild and Rapid 1,2ーTransーGlycosidation Method via BenzoylーProtected Glycoーpyranosyl P,PーDiphenylーNー(pーToluenesulfonyl)Phosphinimidates" Heterocycles. 30. 775-778 (1990)

Shunichi Hashimoto：“通过苯并保护的吡喃糖基 P,P-二苯基-N-(对甲苯磺酰基) 膦酰亚胺酯进行温和快速的 1,2-反式糖苷化方法” 30. 775-778 (1990)。

橋本 俊一: "An Efficient Construction of 1,2ーtransーβーglycosidic Linkages via BenzylーProtected Glycopyranosyl P,PーDiphenylーNー(pーToluenesulfonyl)Phosphinimidates." Chem.Pharm.Bull.38. 2323-2325 (1990)

Shunichi Hashimoto：“通过受苄基保护的吡喃葡萄糖基 P,P-二苯基-N-(对甲苯磺酰基)磷酸亚胺酯有效构建 1,2-反式-β-糖苷键。Chem.Pharm.Bull.38。” (1990)

Shun-ichi Hashimoto: "A Stereocontrolled Construction of 2-Deoxy-beta-glycosidic Linkages via 1,2-trans-beta-Glycosidation of 2-Deoxy-2-[(p- methoxyphenyl)thio]glyco-pyranosyl N,N,N',N'-Tetramethylphosphoroamidates" Chemistry Letters. 1511-1514 (1992)

Shun-ichi Hashimoto：“通过 2-脱氧-2-[(对甲氧基苯基)硫基]糖-吡喃糖基 N,N 的 1,2-反式-β-糖苷化来立体控制构建 2-脱氧-β-糖苷键，