Glycosylation with Glycosyl p-Bromophenyl Phthalates as New Efficient Glycosyl Donors

Abstract

The development of an efficient and stereoselective glycosylation methodology has been a major concern in synthetic organic chemistry in the past a decade due to the important biological functions of complex oligosaccharides and glycoconjugates. Devising new glycosyl donors and developing new activation systems for the existing donors resulted in major advances in this area. For example, several glycosylation methodologies using the efficient glycosyl donors such as thioglycosides, glycosyl sulfoxides, glycals, glycosyl trichloroacetimidates, n-pentenyl glycosides, and glycosyl fluorides have been available. In addition, there have been recent reports regarding the development of glycosylation methods via new glycosyl donors and the application of existing glycosyl donors in novel activation systems. However, there still remains a need for more efficient and generally applicable new glycosylation methodology. In our previous endeavors, we reported a novel type of glycosyl donors, the 2’-(benzyloxycarbonyl)benzyl (BCB) glycoside and the 2’-carboxybenzyl (CB) glycoside A, as shown in Figure 1 for the stereoselective β-mannopyranosylation and the 2-deoxyglycosylation. We applied this methodology to the synthesis of a trisaccharide and tetrasaccharide. More recently, we have also reported the synthesis of the glycosyl benzyl phthalate C and its use as a new type of glycosyl donor. Although the glycosyl benzyl phthalate C proved to be the efficient glycosyl donor, there still remains a need for improvement. Thus, it is desirable to conduct the glycosylation more efficiently and at lower temperature in order to control the stereochemistry of the product and to keep acid-labile reactants or products intact under the acidic condition resulting from the use of TMSOTf. We envisaged that certain glycosyl aryl phthalates D might be more reactive than C so that the glycosylation might be conducted at lower temperature. Herein we describe the synthesis of a new type of glycosyl donors, the glycosyl aryl phthalate D and report that the glycosylation with glycosyl p-bromophenyl phthalates could be conducted under milder condition than that with glycosyl benzyl phthalates.