Picolinyl-Assisted Approaches to Stereocontrolled Glycosylation

Although carbohydrates are the most abundant molecules on Earth, our current knowledge of these fascinating natural compounds is still limited. Some aspects that are already known include the carbohydrate involvement in damaging cellular processes such as bacterial and viral infections, development of tumors, metastasis, septic shock, etc. Consequently the development of effective methods for the synthesis, isolation, analysis, and investigation of complex carbohydrates has become critical in all areas of glycoscience. Among various focus areas, stereocontrolled glycosylation has emerged as a topic of particular importance. Yet, it remains a remarkable challenge to chemists because a new chirality center is formed during glycosylation. A failure to control the stereoselectivity of glycosylation reactions will typically lead to mixtures of 1,2-cis and 1,2-trans diastereomers. The aim of stereocontrolling of glycosylation has been approached in a variety of ways and the effect of a neighboring acyl participating group has been among the most powerful stereodirecting factors known to date for obtaining 1,2-trans glycosides. The work presented herein is dedicated to broadening the scope of the stereodirected glycosylation using the concept of participating groups. Novel to this approach is the development of a well-rounded methodology that allows for synthesizing either 1,2-cis or 1,2-trans glycosides by simple switching of protecting groups. This is accomplished via novel glycosyl donors equipped either with picolinyl (2-pyridylmethyl ether) or picoloyl (2-pyridylcarbonyl ester) groups. A mechanistic understanding of various modes of action of these groups enhanced our ability to perform stereodirected glycosylations with exceptional stereoselectivity. This led to the development of a novel concept to stereocontrolled glycosylation that we named Hydrogen-bond-mediated Aglycone Delivery (HAD). The HAD concept has been extended to the synthesis of various linear and branched oligosaccharides and broadening of all aspects of the methodology. Furthermore, this study evolved into the development of a new type of glycosyl donors allowing for switchable stereoselectivity

Synthesis of 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-manno derivatives as versatile building blocks

Reported herein is the synthesis of a number of building blocks of 2-amino-2-deoxy-d-mannose from common d-glucose precursors.Bio-organic Synthesi

Bromine-promoted glycosidation of conformationally superarmed thioglycosides

Presented herein is our study of the conformation and reactivity of highly reactive thioglycoside donors. The structural studies have been conducted using NMR spectroscopic and computational methods. The reactivity of these donors has been investigated in bromine-promoted glycosylations of aliphatic and sugar alcohols. Swift reaction times, high yields, and respectable 1,2-cis stereoselectivity were observed in a majority of these glycosylations

Glycosidation of Thioglycosides in the Presence of Bromine: Mechanism, Reactivity, and Stereoselectivity

Elaborating on previous studies by Lemieux for highly reactive “armed” bromides, we discovered that β-bromide of the superdisarmed (2-<i>O</i>-benzyl-3,4,6-tri-<i>O</i>-benzoyl) series can be directly obtained from the thioglycoside precursor. When this bromide is glycosidated, α-glycosides form exclusively; however, the yields of such transformations may be low due to the competing anomerization into α-bromide that is totally unreactive under the established reaction conditions

Conformationally superarmed S-ethyl glycosyl donors as effective building blocks for chemoselective oligosaccharide synthesis in one pot

A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete β-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning