Stereodirecting Effect of the Pyranosyl C-5 Substituent in Glycosylation Reactions
Stereodirecting Effect of the Pyranosyl C-5 Substituent in Glycosylation Reactions
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DOI：
10.1021/jo900662v
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发表时间：
2009-07-17
影响因子：
3.6
通讯作者：
van der Marel, Gijsbert A.
中科院分区：
文献类型：
--
作者：
Dinkelaar, Jasper;de Jong, Ana Rae;van der Marel, Gijsbert A.
在一系列D-吡喃糖基硫代糖苷供体中研究了糖基C-5取代基的立体定向效应，并与它们在中间体H-3（4）和H-4（3）半椅氧杂卡宾离子中的优选位置有关。计算研究表明，轴向定位的C-5羧酸酯可以通过将来自其羰基官能团的电子密度提供给贫电子的氧杂碳烯鎓离子官能团来稳定（3）H4半椅型氧杂碳烯鎓离子构象。通过C-5苄氧基甲基可以实现类似的稳定化，但是这种稳定化的程度明显小于C-5羧酸酯。结果，与C-5羧酸酯相比，C-5苄氧基甲基占据半椅型氧杂卡宾鎓离子中的轴向位置的偏好大大降低。为了使空间相互作用最小化，C-5甲基倾向于采用赤道位置，因此有利于H-4（3）半椅型氧杂卡宾离子。当所有的吡喃糖基取代基占据它们在两个中间体半椅氧杂卡宾离子之一中的有利位置时，可以实现高度立体选择性的糖基化，如甘露糖醛酸酯的优异的β-选择性和6-脱氧古洛糖苷的α-选择性所揭示的。
The stereodirecting effect of the glycosyl C-5 substituent has been investigated in a series of D-pyranosyl thioglycoside donors and related to their preferred positions in the intermediate H-3(4) and H-4(3) half-chair oxacarbenium ions. Computational studies showed that an axially positioned C-5 carboxylate ester can stabilize the (3)H4 half-chair oxacarbenium ion conformer by donating electron densit from its carbonyl function into the electron-poor oxacarbenium ion functionality. A similar stabilization can be achieved by a C-5 benzyloxyrnethyl group, but,the magnitude of this stabilization is significantly smaller than for the C-5 carboxylate ester. As a result, the preference of the C-5 benzyloxymethyl to occupy an axial position in the half-chair oxacarbenium ions is much reduced compared to the C-5 carboxylate ester. To minimize steric interactions, a C-5 methyl group prefers to adopt an equatorial position and therefore favors the H-4(3) half-chair oxacarbenium ion. When all pyranosyl substituents occupy their favored position in one of the two intermediate half-chair oxacarbenium ions, highly stereoselective glycosylations can be achieved as revealed by the excellent beta-selectivity of mannuronate esters and alpha-selectivity of 6-deoxygulosides.