Automated Chemical Oligosaccharide Synthesis: Novel Approach to Traditional Challenges.

Advances in carbohydrate chemistry have certainly made common oligosaccharides much more accessible. However, many current methods still rely heavily upon specialized knowledge of carbohydrate chemistry. The application of automated technologies to chemical and life science applications such as genomics and proteomics represents a vibrant field. These automated technologies also present opportunities for their application to organic synthesis, including that of the synthesis of oligosaccharides. However, application of automated methods to the synthesis of carbohydrates is an underdeveloped area as compared to other classes of biomolecules. The overarching goal of this review article is to present the advances that have been made at the interface of carbohydrate chemistry and automated technology.

Manual and Automated Syntheses of the N-Linked Glycoprotein Core Glycans.

Presented herein are two complementary approaches to the synthesis of the core N-glycan pentasaccharide. The first, a traditional manual approach in solution, makes use of the H-bond-mediated aglycone delivery method for the highly diastereoselective introduction of the ß-mannosidic linkage at room temperature. The synthesis of the core pentasaccharide was also accomplished using an high-performance liquid chromatography-assisted automated approach. The overall assembly was swift (8 h) and efficient (31%).

OFox imidates as versatile glycosyl donors for chemical glycosylation.

Previously we communicated 3,3-difluoroxindole (HOFox) - mediated glycosylations wherein 3,3-difluoro-3H-indol-2-yl (OFox) imidates were found to be key intermediates. Both the in situ synthesis from the corresponding glycosyl bromides and activation of the OFox imidates could be conducted in a regenerative fashion. Herein, we extend this study with the main focus on the synthesis of various OFox imidates and their investigation as glycosyl donors for chemical 1,2-cis and 1,2-trans glycosylation.

HPLC-Assisted Automated Oligosaccharide Synthesis: Implementation of the Autosampler as a Mode of the Reagent Delivery.

The development of a useful methodology for simple, scalable, and transformative automation of oligosaccharide synthesis that easily interfaces with existing methods is reported. The automated synthesis can now be performed using accessible equipment where the reactants and reagents are delivered by the pump or the autosampler and the reactions can be monitored by the UV detector. The HPLC-based platform for automation is easy to setup and adapt to different systems and targets.

Electrochemical impedance spectroscopy study of carbohydrate-terminated alkanethiol monolayers on nanoporous gold: Implications for pore wetting.

Electrochemical impedance spectroscopy (EIS) is used to compare the apparent electron transfer rate constant (kapp) for a series of alkanethiol and of carbohydrate-terminated alkanethiol self-assembled monolayers (SAMs) on both flat gold and on nanoporous gold (np-Au). Using the surface area for np-Au determined by oxide stripping, the values of kapp for the alkanethiol modified np-Au are initially over two orders of magnitude smaller than the values found on flat Au. This result provides evidence that the diffusing redox probe Fe(CN)63-/4- only accesses a fraction of the np-Au surface after alkanethiol modification suggesting very limited wetting of the internal pores due to the hydrophobic nature of these surfaces. In contrast, for np-Au modified by carbohydrate-terminated (mannose or galactose) alkanethiols the values of kapp are about 10-40 fold smaller than on flat gold, suggesting more extensive access of the diffusing redox probe within the pores and better but still incomplete wetting, a result also found for modification of np-Au with mercaptododecanoic acid. A short chain PEG thiol derivative is found to result in a comparison of kapp values that suggests nearly complete wetting of the internal pores for this highly hydrophilic derivative. These results are of significance for the potential applications of SAM modified np-Au in electrochemical sensors, especially for those based on carbohydrate-protein recognition, or those of np-Au modified by SAMs with polar terminal groups.

Hydrogen-bond-mediated aglycone delivery: focus on ß-mannosylation.

O-Picoloyl groups at remote positions can mediate the course of glycosylation reactions by providing high facial selectivity for the H-bond-mediated attack of the glycosyl acceptor. A new practical method for the stereoselective synthesis of ß-mannosides at ambient temperature is presented.