Callam Christopher S, Gadikota Rajendrakumar Reddy, Krein Douglas M, Lowary Todd L
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, USA.
J Am Chem Soc. 2003 Oct 29;125(43):13112-9. doi: 10.1021/ja0349610.
We report here the combined use of computational chemistry and low-temperature NMR spectroscopy to probe the mechanism of a highly stereoselective glycosylation reaction employing 2,3-anhydrofuranosyl glycosyl sulfoxides (2 and 4). The reaction involves a two-step process that is carried out in one pot. In the first step, the sulfoxide is reacted with triflic anhydride leading to the formation of a single intermediate. Using NMR spectroscopy, we have established the structure of this intermediate as a glycosyl triflate. In the second step, the acceptor alcohol is added to the reaction mixture, which leads to the highly stereocontrolled formation of the glycoside product. The structure of the major product is consistent with a pathway involving an S(N)2-like displacement of the triflate by the alcohol. In the predominant intermediate that is formed, there is a trans relationship between the triflate group and epoxide. Therefore, in the glycoside product there is a cis relationship between the epoxide and the aglycone. In addition to providing insight into these reaction pathways, these investigations have also allowed us to identify conditions under which the glycosylations can be made to proceed with even greater stereoselectivity and in higher yield.
我们在此报告结合使用计算化学和低温核磁共振光谱来探究采用2,3-脱水呋喃糖基糖基亚砜（2和4）的高度立体选择性糖基化反应的机理。该反应涉及在一个反应瓶中进行的两步过程。第一步，亚砜与三氟甲磺酸酐反应，生成单一中间体。利用核磁共振光谱，我们已确定该中间体的结构为糖基三氟甲磺酸酯。第二步，将受体醇加入反应混合物中，从而导致糖苷产物的高度立体控制形成。主要产物的结构与涉及醇对三氟甲磺酸酯进行类似SN2取代的途径一致。在形成的主要中间体中，三氟甲磺酸酯基团与环氧化物之间存在反式关系。因此，在糖苷产物中，环氧化物与糖苷配基之间存在顺式关系。除了深入了解这些反应途径外，这些研究还使我们能够确定可使糖基化反应以更高的立体选择性和更高的产率进行的条件。
