Recent advances in glycosylation reactions
Recent advances in glycosylation reactions
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糖基化反应的最新进展
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发表时间：
1979
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通讯作者：
P. Sinaÿ
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作者：
P. Sinaÿ
提出了几种有效和选择性制备糖苷的新方法。商业三（4-溴苯基）铵基六氯锑酸盐，一种单电子转移均相试剂，在乙腈中很好地活化在C-2处具有参与或非参与取代基的各种乙基或苯基S-糖苷，以高产率得到β-O-糖苷。在主题的变体中，苯基S-糖苷在温和的电化学条件下与醇反应，得到相应的O-糖苷。叠氮基黄原酸酯，通过两步序列从各种半乳糖制备，是有效的半乳糖基供体的立体选择性合成的生物重要的含半乳糖胺的寡糖的保护前体。我们还发现异头烯醇醚或相应的碳酸酯是非常有效的糖基供体。最后，基于适当的无环烯醇醚的碘环化的“非正统”策略导致了含KDO的二糖的新方法。这最后的合成关键受益于使用的特伯试剂的关键起始烯醇醚的制备。简单，有效和选择性的制备低聚糖是碳水化合物化学的一个中心问题。Koenigs和Knorr在1901年的历史性出版物中首次引入了糖基卤化物作为糖基供体（参考文献1），并推出了一种方法，该方法经过一系列的变化，在很长一段时间内基本上是必不可少的（参考文献2，3）。原酸酯法的引入可能是寻找柯尼希斯-克诺尔法替代方法的第一次重要尝试（参考文献4）。多年来，这种反应主要是由俄罗斯学派（参考文献5、6）加以改进。对卤代糖的化学性质的微妙理解导致了1975年Lemieux等人的发展。(ref. 7，8）的卤化物催化的糖基化反应，已成功地应用于几个血型抗原决定簇的合成。这种变化在主题上的限制是缺乏与许多具有弱反应能力的“糖醇”的反应性，通常是甲基2，3，6-三-O-苄基-α-α-吡喃葡萄糖苷（Rf. 9)近年来，它已成为评价任何新糖基化策略的“道路保持性”的标准。1978年，我们公开了亚胺化方法（参考文献10），这是一种新的可替代Koenigs-Knorr反应的方法。我们最初方法的缺点--从卤代糖合成糖基供体相当费力--被R. R.施密特等（参考文献11），亚氨酸酯糖基化反应现在在该领域有更多的用途。重要的是要强调，三氯乙酰亚胺酯与乙酰亚胺酯相比高得多的反应性可能对α-选择性有害。事实上，温和的乙酰亚胺酯糖基化反应是高度选择性的，这是在处理足够反应性的受体时应该记住的明显优势。这一研究可能有助于进一步远离柯尼希斯和克诺尔在世纪之交引入的时间抗拒“范式”。随着有效的糖基供体的可用性最终为具有生物相关性的更高寡糖铺平了道路，一个实际的困难很快出现了：为了将复杂寡糖片段的操作保持在最低限度，并完全明确方便的合成，构建在活化后可以直接转移到受体的模块似乎很重要。在这方面，硫代糖苷类正引起相当大的关注（参考文献12）。它们在各种化学转化下是稳定的，并且可以被亲硫试剂活化。本讲座分析了作者实验室在糖基化领域的最新研究成果，主要分为四个主题。1)用TBPA+“（单电子转移均相试剂）或通过阳极氧化（非均相单电子转移）活化硫代糖苷。2)2-叠氮基-2-脱氧-D-吡喃半乳糖基衍生物的异头S-黄原酸酯作为有效糖基供体的用途。3)异头烯醇醚或相应碳酸酯作为新型糖基供体的合成和用途。4)开发用于合成含KDO的二糖的“非正统”策略。519
Several novel solutions to the efficient and selective preparation of glycosides are presented. Commercial tris(4-bromophenyl)aniumyl hexachloroantimonate, a one-electron transfer homogeneous reagent, nicely activates in acetonitrile various ethyl or phenyl S-glycosides having either participating or non-participating substituents at C-2 to give p-0-glycosides in good yield. In a variation on the theme, phenyl S-glycosides react with alcohols under mild electrochemical conditions to give the corresponding 0-glycosides. Azidoxanthates, prepared via a two-step sequence from various galactals, are efficient galactosyl donors for the steroselective synthesis of protected precursors of biologically important galactosamine-containing oligosaccharides. We have also discovered that anomeric enol-ethers, or the corresponding carbonates, are remarkably efficient glycosyl donors. Finally, a "non-orthodox" strategy based on the idocyclization of appropriate acyclic enol-ethers resulted in a novel approach to KDO-containing disaccharides. This last synthesis critically benefited from the use of the Tebbe reagent for the preparation of the key starting enol ethers. INTRODUCTION Simple, efficient and selective preparation of oligosaccharides is a central problem in carbohydrate chemistry. The historical publication of Koenigs and Knorr, in 1901, first introduced glycosyl halides as glycosyl donors (ref.l), and launched a method which -through a vast series of variations -has been by and large the essential one for a very long period of time (ref. 2, 3). The introduction of the orthoester procedure was probably the first important attempt to find an alternative to the Koenigs-Knorr method (ref. 4). This reaction has been refined over the years, mainly by the Russian School (ref. 5, 6). A subtle understanding of the chemical properties of the halogeno sugars resulted in 1975 in the development by Lemieux et aZ.(ref. 7, 8) of the halide-catalyzed glycosylation reaction which has been successfully applied to the synthesis of several blood group antigenic determinants. A limitation of this variation on the theme was the lack of reactivity with many "sugar alcohols" with weak reacting capacities, typically methyl 2,3,6-tri-0-benzyl-a-~-glucopyranoside (r f. 9) which has become, over recent years, a standard for evaluating the "road holding" of any novel glycosylation strategy. In 1978 we disclosed the imidate procedure (ref. lo), a novel alternative to the Koenigs-Knorr reaction. The disadvantage of our original procedure -a rather laborious synthesis of the glycosyl donor from a halogeno sugar -was circumvented by R. R. Schmidt et al. (ref. 11) and the imidate glycosylation reaction is now of much more use in the field. It is important to stress that the much higher reactivity of trichloroacetimidates compared to acetimidates may be detrimental to the a-selectivity. Indeed, the mild acetimidate glycosylation reaction is highly selective, a distinct advantage which should be kept in mind when dealing with sufficiently reactive acceptors. This research has probably contributed to moving further and further away from the time-resistant "paradigm" introduced by Koenigs and Knorr at the turn of the century. With the availability of efficient glycosyl donors paving at last the avenue to higher oligosaccharides of biological relevance, a practical difficulty soon emerged: in order to keep manipulation of complex oligosaccharide fragments to a minimum, and to fully explicit convenient synthesis, it appeared important to build blocks which could be directly transferred to an acceptor upon activation. Thioglycosides are now attracting considerable attention in this respect (ref. 12). They are stable under a variety of chemical transformations and can be activated by thiophilic reagents. Recent results obtained in the author's laboratory in the field of glycosylation are now being analyzed in this lecture which can be divided into four main topics. 1) Activation of thioglycosides with either TBPA+', a one-electron transfer homogeneous reagent, or via anodic oxidation (heterogeneous one-electron transfer). 2) Use of anomeric S-xanthates of 2-azido-2-deoxy-D-galactopyranosyl derivatives as efficient glycosyl donors. 3) Synthesis and use of anomeric enol-ethers, or the corresponding carbonates, as novel glycosyl donors. 4) Development of "non-orthodox" strategies for the synthesis of KDOcontaining disaccharides. 519