Chemical Synthesis of Oligosaccharides: Effects of Leaving Groups and Remote Protecting Groups of Donors on Glycosylation Stereochemistry

다국어 초록 (Multilingual Abstract)

Development of efficient and stereoselective glycosylation methodologies has been a major concern in synthetic organic chemistry over the past decade due to important roles of complex oligosaccharides in many fundamental life-sustaining processes. The selection of an appropriate glycosyl donor is one of the key processes for the successful glycosylation in terms of efficiency and stereoselectivity. We reported previously a new direct glycosylation method with anomeric hydroxy sugars as donors and phthalic anhydride and triflic anhydride as promoters, and the result of investigation of intermediates in the new glycosylation by low temperature NMR [1]. Although our direct glycosylation method works nicely in various glycosylations including stereoselective β-mannosylations, in certain cases, it gives undesired self-condensed esters of donors. In the first part of the lecture is presented a modified, improved method for the direct glycosylation with anomeric hydroxy sugars by employing phthalic anhydride derivatives in the place of phthalic anhydride itself. One of the most useful stereoselective glycosylation strategy utilizing protecting groups has been the 1,2-trans glycoside synthesis. Although the acyl groups at O-2 of donors give 1,2-trans glycosides by the neighboring group participation, their electron-withdrawing effects on the glycosylation stereochemistry might not have been properly recognized because of the overwhelming effect of the neighboring group participation. In fact, the effect of the non-participating electron-withdrawing groups such as methanesulfonyl and benzylsulfonyl groups at the O-2 positions of the donors on the glycosylation stereochemistry has been observed. Remote electron-withdrawing groups at O-3, O-4, and O-6 positions of pyranosyl donors or at O-3 and O-5 positions of furanosyl donors, which would reduce the reactivity of glycosyl donors, might also exert directing effects on the outcome of the stereochemistry of glycosylations. In fact, we reported previously that mannosylations of various acceptors with donors possessing an electron-withdrawing sulfonyl or acyl groups at O-3, O-4, or O-6 positions were found to be β-selective except when donors had 3-O-acyl and 6-O-acetyl groups, which afforded α-mannosides as major products [2]. The α-directing effect of 3-O-acyl and 6-O-acetyl groups was attributed to their remote participations while the origin of the β-directing effect was ascribed to the SN2-like reaction of the acceptor and the α-triflate intermediate, which is stabilized by remote electron-withdrawing groups. In the second part of the lecture is concerned with the directing effect of electron-withdrawing groups at the remote positions of donors on the stereochemistry in not only mannosylations but also other glycosylations. Directing effect of remote electron-withdrawing groups of other glycosyl donors was found to be quite different from the directing effect of those of mannosyl donors.