Facile C1 Epimerization of alpha-1-sulfonamidyl-2-deoxy-2-iodo- glycopyranosides.
Facile C1 Epimerization of alpha-1-sulfonamidyl-2-deoxy-2-iodo- glycopyranosides.
复制标题
α-1-磺酰胺基-2-脱氧-2-碘-吡喃糖苷的简单 C1 差向异构化。
DOI：
10.1021/jo001161o
复制
发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Petillo,PA
中科院分区：
文献类型：
--
作者：
Owens,JM;Yeung,BK;Hill,DC;Petillo,PA
2-氨基-2-脱氧糖苷是糖胺聚糖1,2和许多其他生物学上重要的糖类的重要组成部分。Danishefsky碘磺化方法已被证明是一种合成和偶联这些糖的有效方法，并已成功地应用于许多重要的合成。4-6在这个过程中，1,2 -糖基，1，通过I（对称-colidine） 2ClO4和磺胺（方案1）转化为其跨二轴- 1,2 -碘磺酰胺对应物，3。在糖基受体存在的情况下，用LiTMP和AgOTf处理反式- 1,2 -碘磺酰胺中间体，或者在糖基受体的烷基醇存在的情况下，用AgBF4处理反式- 1,2 -碘磺酰胺中间体，会得到β偶联的2-氨基-2-脱氧产物。或者，反式- 1,2 -碘磺酰胺可在适当条件下转化为1-β-硫乙基-2-磺酰胺-2-脱氧产物4a， gh或1-β-叠氮-2-磺酰胺-2-脱氧产物4a， ik。最近，当我们尝试用这种方法合成糖胺聚糖片段时，5,7我们遇到了一些在任何条件下都不能与糖基受体偶联的碘磺酰胺。虽然我们最初认为这是偶联过程的失败，但对底物的更仔细检查显示，从标准Danishefsky方案中分离出的物质不是预期的跨二轴- 1,2 -碘磺酰胺，3，而是它的C1外显体，6。在尝试使用碘磺胺3a时，我们首先遇到了碘磺胺化方法的困难。通过使用标准公布的程序4b，在CH2Cl2中，三o -苄基- d -葡聚糖1a与对硝基苯磺酰胺在室温下反应1小时，得到碘磺酰胺6a，其立体化学只有在仔细的NOE研究后才能确定（图1）。对碘磺化反应的时间和温度研究表明，在10℃下5分钟后，3a的产率很高，但在1小时内定量转化为6a。尽管我们付出了很大的努力，但我们没有找到阻止3a异构化到6a的条件。因为3到5的反应是通过氮化吡啶中间体4进行的，所以C1外映体6对任何偶联条件都是惰性的。
2-Amino-2-deoxy glycosides are essential components of glycosaminoglycans1, 2 and many other biologically important saccharides. 3 The Danishefsky iodosulfonamidation methodology has proven to be a powerful method for the synthesis and coupling of these sugars and has been successfully employed in a number of important syntheses. 4-6 In this procedure, a 1, 2-glycal, 1, is transformed to its trans-diaxial-1, 2-iodosulfonamide counterpart, 3, via treatment with I (sym-colidine) 2ClO4 and a sulfonamide (Scheme 1). Treatment of the trans-1, 2-iodosulfonamide intermediate with LiTMP and AgOTf in the presence of a glycosyl acceptor or with AgBF4 in the presence of the stannyl alkoxide of the glycosyl acceptor results in β-coupled 2-amino-2-deoxy product. 4a-d Alternatively, the trans-1, 2-iodosulfonamide can be converted to the 1-β-thioethyl-2-sulfonamidyl-2-deoxy product, 4a, gh or the 1-β-azido-2-sulfonamidyl-2-deoxy product, 4a, ik under the appropriate conditions. Recently, while attempting to employ this procedure in a synthesis of glycosaminoglycan fragments, 5, 7 we encountered a number of iodosulfonamides which would not couple to a glycosyl acceptor under any conditions.While we originally thought this a failing of the coupling procedures, closer examination of the substrates revealed that the material isolated from the standard Danishefsky protocol was not the expected trans-diaxial-1, 2-iodosulfonamide, 3, but rather its C1 epimer, 6. We first encountered difficulties with the iodosulfonamidation methodology while attempting to utilize iodosulfonamide 3a. Through use of the standard published procedure, 4b the reaction of tri-O-benzyl-D-glucal, 1a, in CH2Cl2 with p-nitrobenzenesulfonamide at room temperature for 1 h resulted in iodosulfonamide, 6a, whose stereochemistry was ascertained only after a careful NOE study (Figure 1). A time and temperature study of the iodosulfonamidation reaction revealed that after five minutes at-10 C, 3a is formed in good yield but is quantitatively converted to 6a in 1 h. Despite intensive effort, we failed to find conditions that prevented the isomerization of 3a to 6a. Because the reaction of 3 to 5 proceeds via the aziridine intermediate, 4, the C1 epimer, 6, is inert to any coupling conditions.