Oxazolidinone protected 2-amino-2-deoxy-D-glucose derivatives as versatile intermediates in stereoselective oligosaccharide synthesis and the formation of α-linked glycosides
Oxazolidinone protected 2-amino-2-deoxy-D-glucose derivatives as versatile intermediates in stereoselective oligosaccharide synthesis and the formation of α-linked glycosides
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DOI：
10.1021/ja0162109
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发表时间：
2001-09-26
影响因子：
15
通讯作者：
Kerns, RJ
中科院分区：
文献类型：
--
作者：
Benakli, K;Zha, CX;Kerns, RJ
许多天然产物和具有生物学意义的糖缀合物含有N-取代的2-氨基-2-脱氧-D-吡喃葡萄糖苷残基。1我们最近一直在探索将结构多样性引入这些重要糖缀合物的一个家族，即糖胺聚糖（GAG）。2合成GAG寡糖以及含有2-氨基-2-脱氧-D-吡喃葡萄糖苷残基的其他糖缀合物的主要障碍是难以容易地制备在糖苷键形成反应期间也显示出高立体选择性的结构多样的2-氨基糖。在这里，我们报告的1-苯硫基-吡喃葡萄糖苷的环稠合2，3-恶唑烷酮衍生物的合成，并证明这些新的糖基供体和合成中间体的立体选择性寡糖合成和R-连接的糖苷的形成的效用。虽然有许多策略来获得“β-连接的”2-氨基-D-吡喃葡萄糖苷3（在透明质酸盐和硫酸皮肤素GAG中发现），但“R-连接的”2-氨基-D-吡喃葡萄糖苷（在肝素和硫酸乙酰肝素（HS）GAG中发现）的形成几乎完全依赖于使用2-叠氮基-糖基供体。4 2-叠氮基供体的糖苷化提供偶联产物的R/β-混合物，尽管R-异构体通常占主导地位。制备2-叠氮基糖的方法通常也是昂贵的并且通常是低效的，对经由这些中间体合成的糖缀合物的商业化造成限制。此外，含有多个不同的N-取代的R-连接的2-氨基糖的寡糖的合成受到严重限制，因为这些合成必须使用2-叠氮基供体用于每个糖苷形成反应，使得区分多个胺基团成为问题。制备含半乳糖胺的糖缀合物（例如硫酸软骨素和糖肽）的另一个显著障碍是半乳糖胺衍生物作为合成中间体的高成本和难以获得。为了解决这些问题，我们设想了苯基2-氨基-2-脱氧-1-硫代-吡喃葡萄糖苷的环稠合2，3-恶唑烷酮衍生物作为立体选择性合成R-连接和β-连接的糖缀合物的通用中间体。恶唑烷酮5是靶向的第一种常见中间体（方案1）。苯硫基保护异头位置，直到选择性活化形成糖苷键。6通过稠合恶唑烷酮环促进5中所有羟基的选择性分化，其保护和分化C-3羟基。
Many natural products and biologically significant glycoconjugates contain N-substituted 2-amino-2-deoxy-D-glycopyranoside residues. 1 We have recently been exploring the introduction of structural diversity into one family of these important glycoconjugates, the glycosaminoglycans (GAGs). 2 A major obstacle to synthesizing GAG oligosaccharides, as well as other glycoconjugates containing 2-amino-2-deoxy-D-glycopyranoside residues, is the difficulty to readily prepare structurally diverse 2-amino sugars that also display high stereoselectivity during glycoside bond-forming reactions. Here, we report the synthesis of ringfused 2, 3-oxazolidinone derivatives of 1-phenylthio-glycopyranosides and demonstrate the utility of these novel glycosyl donors and synthetic intermediates in stereoselective oligosaccharide synthesis and the formation of R-linked glycosides. While there are a number of strategies to obtain “β-linked” 2-amino-D-glycopyranosides3 (found in hyaluronate and dermatan sulfate GAGs), the formation of “R-linked” 2-amino-D-glucopyranosides (found in heparin and heparan sulfate (HS) GAGs) relies almost exclusively on employing 2-azido-glycosyl donors. 4 Glycosidation of the 2-azido donors affords R/β-mixtures of the coupled products, although the R-isomer usually predominates. Methods to prepare the 2-azido sugars are also generally expensive and often inefficient, posing limitations to commercialization of glycoconjugates synthesized via these intermediates. 5 Moreover, the synthesis of oligosaccharides containing multiple different N-substituted R-linked 2-amino sugars is severely limited because these syntheses must use 2-azido donors for each glycoside forming reaction, making it problematic to differentiate the multiple amine groups. An additional significant obstacle to preparing galactosamine-containing glycoconjugates (eg chondroitin sulfates and glycopeptides) is the high cost and inaccessibility of galactosamine derivatives as synthetic intermediates. In an effort to address these problems, we envisioned ringfused 2, 3-oxazolidinone derivatives of phenyl 2-amino-2-deoxy-1-thio-glucopyranosides as versatile intermediates for the stereoselective synthesis of R-linked and β-linked glycoconjugates.(Figure 1).Oxazolidinone 5 was the first common intermediate targeted (Scheme 1). The phenylthio group protects the anomeric position until selectively activated for glycoside bond formation. 6 Selective differentiation of all hydroxyl groups in 5 is facilitated by the fused oxazolidinone ring, which protects and differentiates the C-3 hydroxyl group.