Two-step synthesis of carbohydrates by selective aldol reactions
Two-step synthesis of carbohydrates by selective aldol reactions
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DOI：
10.1126/science.1101710
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发表时间：
2004-09-17
期刊：
影响因子：
56.9
通讯作者：
MacMillan, DWC
中科院分区：
文献类型：
--
作者：
Northrup, AB;MacMillan, DWC
由于缺乏快速构建和偶联差异保护单糖的化学策略，碳水化合物的研究受到阻碍。在这里，提出了一种基于三种醛的羟醛偶联的合成路线，用于在仅两个化学步骤中从头生产多元醇分化的己糖。在L-脯氨酸催化下的α-羟基醛的二聚反应之后，接着是由刘易斯酸催化的串联的Mukaiyama羟醛加成-环化步骤。通过简单地改变所用的溶剂和刘易斯酸，可以以高产率和立体化学纯度分别选择不同保护的葡萄糖、阿洛糖和甘露糖立体异构体。该反应序列还有效地产生C-13标记的类似物，以及结构变体，如2-氨基和2-硫代取代的衍生物。
Studies of carbohydrates have been hampered by the lack of chemical strategies for the expeditious construction and coupling of differentially protected monosaccharides. Here, a synthetic route based on aldol coupling of three aldehydes is presented for the de novo production of polyol differentiated hexoses in only two chemical steps. The dimerization of alpha-oxyaldehydes, catalyzed by L-proline, is then followed by a tandem Mukaiyama aldol addition-cyclization step catalyzed by a Lewis acid. Differentially protected glucose, allose, and mannose stereoisomers can each be selected, in high yield and stereochemical purity, simply by changing the solvent and Lewis acid used. The reaction sequence also efficiently produces C-13-labeled analogs, as well as structural variants such as 2-amino- and 2-thio-substituted derivatives.