Boronic-Acid-Catalyzed Regioselective and 1,2-cis-Stereoselective Glycosylation of Unprotected Sugar Acceptors via SNi-Type Mechanism

作者：Masamichi Tanaka, Akira Nakagawa, Nobuya Nishi, Kiyoko Iijima, Ryûichi Sawa, Daisuke Takahashi, Kazunobu Toshima · 发表于：Journal of the American Chemical Society · 年份：2018 · DOI：10.1021/jacs.7b12108 · 被引用次数：147 · 研究领域：Carbohydrate Chemistry and Synthesis、Glycosylation and Glycoproteins Research、Enzyme Production and Characterization

Regio- and 1,2- cis -stereoselective chemical glycosylation of unprotected glycosyl acceptors has been in great demand for the efficient synthesis of natural glycosides. However, simultaneously regulating these selectivities has been a longstanding problem in synthetic organic chemistry. In nature, glycosyl transferases catalyze regioselective 1,2- cis -glycosylations via the S N i mechanism, yet no useful chemical glycosylations based on this mechanism have been developed. In this paper, we report a highly regio- and 1,2- cis -stereoselective S N i-type glycosylation of 1,2-anhydro donors and unprotected sugar acceptors using p -nitrophenylboronic acid ( 10e ) as a catalyst in the presence of water under mild conditions. Highly controlled regio- and 1,2- cis -stereoselectivities were achieved via the combination of boron-mediated carbohydrate recognition and the S N i-type mechanism. Mechanistic studies using the KIEs and DFT calculations were consistent with a highly dissociative concerted S N i mechanism. This glycosylation method was applied successfully to the direct glycosylation of unprotected natural glycosides and the efficient synthesis of a complex oligosaccharide with minimal protecting groups.