Rapid Synthesis of Oligosaccharides Based on One-Pot Glycosylation

Abstract

In this study, biologically active oligosaccharides were synthesized based on one-pot glycosylation. Onepot glycosylation enables direct coupling of multisaccharide building blocks via sequential chemo-and regioselective glycosylations in a single vessel. A di-branched heptasaccharide was synthesized by one-pot glycosylation using seven independent building blocks. The glycosyl amino acids containing sialic acids were covered by the onepot glycosylation, in which sialylation was achieved with N-Troc-protected thiosialoside. Combinatorial oligosaccharide libraries were synthesized by one-pot glycosylation using parallel and automated synthesizers. This study also developed a polymer-assisted strategy for deprotection of protected oligosaccharides. A. IntroductionOligosaccharides play important roles in cell surface events via carbohydrate-protein and carbohydrate-carbohydrate interactions (1). The ability to chemically synthesize structurally defined oligosaccharides for structure-function studies is highly advantageous because oligosaccharides from natural sources are available only in limited quantities. Recent progress in oligosaccharide synthesis has resulted in a number of new and efficient glycosidation methodologies ( 2 ) . H o w e v e r, o l i g o s a c c a h r i d e s y n t h e s e s i n v o l v i n g glycosylation and deprotection are difficult to achieve using standard protocols and require well-trained organic chemists. Seeberger and co-workers reported an automated solid-phase oligosaccharide synthesis using a modified solid-phase peptide synthesizer (3). Alternatively, one-pot sequential glycosylation for the synthesis of oligosaccharides was demonstrated by Kahne and co-workers in 1993. In this method an α-linked deoxytrisaccahride was prepared by sequential chemoselective activation of glycosyl sulfoxide and thioglycoside using a single activator (4). One-pot glycosylation enables coupling of multiple building blocks in a single vessel to yield oligosaccharides; the reaction protocols are simple, involving

Automated Chemical Synthesis of Oligosaccharides and Glycoconjugates

“…Similar reactivity scales have also been devised by Fraser-Reid [129], Ley [130][131][132], and others [120]. Takahashi and co-workers probed a number of automation platforms for the solution-based one-pot oligosaccharide synthesis [133]. In a majority of applications, selective activation of different leaving groups, another common approach to expeditious oligosaccharide synthesis [53,67], was executed.…”

“…Using this instrument, Takahashi et al achieved automation of stirring, temperature control, and rate of reagent addition for each glycosylation and deprotection step shown in Fig. 10.9C [133,135]. The synthesis began by the coupling of the fluoride donor (45) with the diol acceptor (44) in the presence of AgOTf as the promoter.…”

Immunotherapy for cancer: synthetic carbohydrate-based vaccines

“…In particular, one-pot multi-step approaches for selective monosaccharide protection45, 46 and oligosaccharide assembly are being pursued, which do not require intermediate work-up and purification steps and hence speed-up the process of chemical synthesis considerably. Several research groups have demonstrated that chemoselective, orthogonal and iterative glycosylation strategies, which exploit differential reactivities of anomeric leaving groups, allow several selected glycosyl donors to react in a specific order resulting in a single oligosaccharide product 47–49, 98–100. Methods for solid phase oligosaccharide synthesis have been reported and these procedures shorten oligosaccharide synthesis by removing the need to purify intermediate derivatives 51, 101…”

Synthesis and Biological Evaluation of the Forssman Antigen Pentasaccharide and Derivatives by a One‐Pot Glycosylation Procedure

“…In a previous study, we reported on an efficient methodology for the synthesis of oligosaccharides based on a one‐pot glycosylation procedure and polymer‐assisted deprotection 8. The one‐pot glycosylation procedure involves the sequential chemo‐ and regioselective glycosylation to directly provide oligosaccharides from several simple building blocks without the need for purifying intermediates and is effective for the synthesis of a single target oligosaccharide as well as oligosaccharide libraries 9.…”