Direct and stereoselective synthesis of 2-acetamido-2-deoxy-β-D-glycopyranosides by using the phosphite method
Direct and stereoselective synthesis of 2-acetamido-2-deoxy-β-D-glycopyranosides by using the phosphite method
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DOI：
10.1002/anie.200461988
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Hashimoto, S
中科院分区：
文献类型：
--
作者：
Arihara, R;Nakamura, S;Hashimoto, S
2-乙酰氨基-2-脱氧-d-甘嘌呤苷是低聚糖和糖缀合物（如糖脂、糖蛋白、蛋白聚糖和肽聚糖）中常见且重要的结构单元，与广泛的生物过程有关2-乙酰氨基-2-脱氧-α-半乳糖吡喃糖残基通过糖苷键连接到丝氨酸和苏氨酸的侧链羟基上，而大多数2-乙酰氨基-2-脱氧-d-甘嘌呤苷被发现为β连接的糖苷。合成2-氨基-2-脱氧糖1,2 -反式β-糖苷的最普遍和最广泛的策略是利用含有参与基的供体作为氨基保护功能，在糖苷化事件后被乙酰基取代。[2,3] 2-叠氮-2-脱氧糖基供体也被用于此目的。[4,5]显然，使用具有天然n -乙酰基功能的供体直接糖苷化方法在效率和实用性方面是一种理想的方法。然而，在实践中，这些给体的反应1通常会导致恶唑啉衍生物3的主要形成，通过邻基参与和随后从NH基团中抽离一个质子（方案1）。[6,7]虽然恶唑啉可以通过恶唑啉离子中间体2或5与受体醇反应生成2-乙酰氨基-2-脱氧-β糖苷4（即恶唑啉方法[8]），这种转化所需的苛刻反应条件阻碍了它在合成复杂低聚糖方面的广泛应用。作为扩展最近开发的糖苷化方法的一部分，该方法利用亚磷酸二乙酯作为离去基[9,10]，我们希望通过直接糖苷化而不通过恶唑啉离子中间体进行立体选择性合成2-乙酰氨基-2-脱氧-β-糖苷。在本研究开始时，我们探索了三甲基硅基三氟甲烷磺酸盐（TMSOTf）促进2-乙酰氨基- 3,4,6 -三- o-苄基-2-脱氧-α-d-葡糖苷化
2-Acetamido-2-deoxy-d-glycopyranosides occur as common and important structural units in oligosaccharides and glycoconjugates, such as glycolipids, glycoproteins, proteoglycans, and peptidoglycans, and are associated with a wide range of biological processes.[1] Whereas 2-acetamido-2-deoxy-α-dgalactopyranose residues are linked through a glycoside bond to the side-chain hydroxy groups of serine and threonine, the majority of 2-acetamido-2-deoxy-d-glycopyranosides are found as β-linked glycosides. The most general and extensively developed strategy for the synthesis of 1, 2-trans-β-glycosides of 2-amino-2-deoxysugars utilizes donors containing a participating group as the amino-protecting functionality, which is replaced by an acetyl group after the glycosidation event.[2, 3] 2-Azido-2-deoxyglycosyl donors have also been used for this purpose.[4, 5] Clearly, a direct glycosidation method by using donors with the natural N-acetyl function would constitute an ideal procedure in terms of efficiency and practicality. In practice, however, the reaction of these donors, 1, generally leads to the predominant formation of oxazoline derivatives 3 through neighboring-group participation and the subsequent abstraction of a proton from the NH group (Scheme 1).[6, 7] Although oxazolines can react with acceptor alcohols in the presence of Brønsted or Lewis acids to afford 2-acetamido-2-deoxy-βglycosides 4 via oxazolinium ion intermediates 2 or 5 (that is, oxazoline method [8]), the harsh reaction conditions required for this conversion have precluded its wide application in the synthesis of complex oligosaccharides. As part of a program to extend the recently developed glycosidation method that capitalizes on diethyl phosphite as a leaving group,[9, 10] we wish to report the stereoselective synthesis of 2-acetamido-2-deoxy-β-glycosides by a direct glycosidation that does not proceed via an oxazolinium ion intermediate. At the outset of this study, we explored the trimethylsilyl trifluoromethanesulfonate (TMSOTf) promoted glycosidation of 2-acetamido-3, 4, 6-tri-O-benzyl-2-deoxy-α-d-glucopyr-