Obadiah J. Plante

Synthesis and Use of Glycosyl Phosphates as Glycosyl Donors

Differentially protected glycosyl phosphates prepared by a straightforward synthesis from glycal precursors are used as powerful glycosyl donors. Activation of beta-glycosyl phosphates by TMSOTf at -78 degrees C achieves the selective formation of beta-glycosidic linkages in excellent yields with complete stereoselectivity. Reaction with thiols results in the conversion of glycosyl phosphates into thioglycosides in nearly quantitative yield. An orthogonal coupling strategy using glycosyl phosphate donors and thioethyl glycoside acceptors allows for the rapid synthesis of a trisaccharide.

A linear synthesis of branched high-mannose oligosaccharides from the HIV-1 viral surface envelope glycoprotein gp120

Described is a linear solution-phase synthesis of the HIV-1 viral surface envelope glycoprotein gp120 high-mannose nonasaccharide pentyl glycoside. Envisioning the automated solid-phase assembly of complex carbohydrates, the synthesis of the nonasaccharide and the related tri- and hexamannosides demonstrates the facile assembly of highly branched structures in a stepwise fashion incorporating monosaccharide building blocks. A differentially protected core trisaccharide was prepared and further elongated in two high-yielding tri-mannosylations to furnish the triantennary structure. The tri-, hexa-, and nonamannoside n-pentyl glycosides obtained via the described synthesis are currently being used for detailed study of the carbohydrate protein interactions responsible for binding of the anti-HIV protein cyanovirin-N to the glycoprotein gp120. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Automated Solid-Phase Synthesis of Hyaluronan Oligosaccharides

Well-defined fragments of hyaluronic acid (HA) have been obtained through a fully automated solid-phase oligosaccharide synthesis. Disaccharide building blocks, featuring a disarmed glucuronic acid donor moiety and a di-tert-butylsilylidene-protected glucosamine part, were used in the rapid and efficient assembly of HA fragments up to the pentadecamer level, equipped with a conjugation-ready anomeric allyl function.

DEVELOPMENT OF AN AUTOMATED OLIGOSACCHARIDE SYNTHESIZER

Publisher Summary This chapter discusses an approach for the development of an automated oligosaccharide synthesizer. To meet the demand for molecular tools, new methods for the rapid production of carbohydrates are needed. Carbohydrates are the most stereochemically challenging class of biopolymers to prepare, and different methods have been developed to address their synthesis. In addition to traditional solution-phase chemical synthesis, three methods—enzymatic methods, orthogonal one-pot chemical methods, and automated solid-phase methods—have become increasingly popular for the construction of oligosaccharides. The chapter develops an automated solid-phase approach for the chemical synthesis of oligosaccharides. In this study, by using an acceptor-bound solid-phase glycosylation strategy in a specially designed instrument, poly α- (1 → 2) mannosides as large as a decasaccharide were synthesized. The use of glycosyl phosphates was demonstrated with the synthesis of a dodecamer phytoalexin elicitor b-glucan. During this investigation, high-resolution magic angle-spinning nuclear magnetic resonance (HR-MAS NMR) analysis was used as an on-resin analytical tool. The method described in the chapter is anticipated to have a significant impact on the field of oligosaccharide synthesis. Although there are still a number of challenges to overcome, the automated construction of glycosidic linkages is expected to allow for the preparation of a diverse set of carbohydrate for pharmaceutical and biochemical evaluation.

Automated synthesis of polysaccharides.

Publisher Summary Carbohydrate synthesis requires the installation of a new stereocenter during each elongation event. The major challenges in carbohydrate synthesis are two-fold: (1) how to control the stereochemistry of each newly formed glycosidic linkage and (2) how to incorporate various degrees of branching. This chapter discusses an automated synthesis method for carbohydrate production. This automated method provides a framework for exploring the potential reaction conditions while at the same time minimizing the amount of effort required to create complex carbohydrates. An automated solid-phase method necessitates a polymer support and a linker that are compatible with the reagents used in carbohydrate synthesis. When initiating a synthesis, the choice of glycosylating agent and protecting groups governs the selection of activating and deblocking reagents. The automated method described in the chapter has proven useful with glycosyl trichloroacetimidate and glycosyl phosphate building blocks. Temporary protecting groups, such as levulinate esters, silyl ethers, and acetate esters also are compatible with automation. Using this set of reagents can help in accessing majority of natural carbohydrate linkages.