二甲基甲醯胺: 獨特的醣質化調控分子

Abstract

此論文成功建立一套藉由預活化(pre-activation)的方式，透過二甲基甲醯胺(dimethylformamide)的調控達到高alpha選擇性醣質化反應。此方法利用二甲基甲醯胺，把高反應性的oxocarbenium ion 轉變成相對反應性較低的glycosyl imidate。之後加入醣受體與上述的glycosyl imidate反應形成醣質化產物。另外，二甲基甲醯胺的當量與alpha選擇性有正相關性。此方法不需要使用特殊的保護基，就能達到極高的alpha選擇性。 利用變溫核磁共振儀(VT-NMR)研究，觀察到alpha-glycosyl imidate的特徵訊號，以及分離出副反應的glycosyl formate。根據以上的證據，提出了此方法合理的反應機制。二甲基甲醯胺與oxocarbenium進行反應產生glycosyl iminium ions 的alpha, beta 混和物(alpha/beta-glycosyl iminium ions)。而beta的glycosyl iminium 反應性比alpha的glycosyl iminium較佳，會先與醣受體進行SN2-like 的反應，產生1,2-cis的醣苷鍵。

A convenient pre-activation DMF-modulating glycosylation method is developed. The method employs DMF as a modulator to convert the highly reactive oxocarbenium ion to less reactive glycosyl imidate; subsequent coupling of the imidate with an acceptor leads to the formation of glycosylation product. In addition, there is a quantity-selectivity relationship between the amount of DMF modulator and the degree of a;pha-selectivity in glycosylation. High to excellent 1,2-cis and 1,2-trans alpha-selectivities are achieved by this simple method without invoking any atypical protecting functions. Regarding the reaction mechanism, VT-NMR study is performed, which clearly identifies the alpha-glycosyl imidate by detection of characteristic signals deriving from the imidate function. In addition, glycosyl formate deriving from the side reaction of the glycosyl donor is also observed on some occasions. Based on such evidence, a possible mechanism is proposed. The interception of oxocarbenium ions with DMF generates a mixture of alpha/beta-glycosyl iminium ions. Empirically, the beta-iminium intermediate is more reactive than the alpha one and is able to react predominantly with the alcohol acceptor through a SN2-like pathway leading to 1,2-cis alpha-glycosidic bond formation.