HPLC‐Based Automated Synthesis of Glycans in Solution

Abstract

As the 21 st century unfolds with rapid changes, new challenges in research and development emerge. These new challenges prompted us to repurpose our HPLCÀ A platform that was previously used in solid phase glycan synthesis to a solution phase batch synthesis described herein. The modular character of HPLC allows for implementing new attachments. To enable sequential synthesis of multiple oligosaccharides with the single press of a button, we supplemented our system with a four-way split valve and an automated fraction collector. This enabled the operator to load all reagents and all reactants in the autosampler, press the button to start the repetitive automation sequence, leave the lab, and upon return find products of multiple reactions ready for purification, analysis, and subsequent application.

Recyclable fluorous-tag assisted two-directional oligosaccharide synthesis enabled by interrupted Pummerer reaction mediated glycosylation

“…The efficacy was exemplified by fast access to the ST14 tetrasaccharide and octasaccharide fragments. Additionally, encouraged by recent remarkable achievements in automated fluorous-assisted solution-phase oligosaccharide synthesis 46 and HPLC-based automated synthesis of glycans in solution, 47 we expect to employ the developed fluorous-tag assisted synthetic strategy in an automated platform and we are currently studying on this issue.…”

Chemical Synthesis of Human Milk Oligosaccharides: para‐Lacto‐N‐hexaose and para‐Lacto‐N‐neohexaose

“…Our lab is engaged in developing HPLCassisted automation technologies for glycan synthesis in solution and polymer supports, [23] and the first efforts to produce HMO in the automated fashion have already emerged. [15] Experimental Section General. The reactions were performed using commercial reagents and the ACS grade solvents used for reactions were purified and dried in accordance with standard procedures.…”

“…Despite this general success, it is apparent that more powerful chemical methods are needed to produce HMO in bulk amount to fully explore their potential health benefits and functional properties. Our lab is engaged in developing HPLC‐assisted automation technologies for glycan synthesis in solution and polymer supports, [23] and the first efforts to produce HMO in the automated fashion have already emerged [15] …”

“…were synthesized using a similar convergent synthetic approach (2+4). Very recently, we applied our HPLC‐based automated approach to the synthesis of lacto‐ N ‐triose (LNTri II) and 3’‐Galactosyllactose (β3’‐GL) core sequences [15] . Reported herein are syntheses of two linear hexasaccharides commonly found in human milk, para ‐lacto‐ N ‐hexaose ( p LNH) 1 and para ‐lacto‐ N ‐neohexaose ( p LNnH) 2 using a convergent 3+3 approach.…”

A Hitchhiker’s Guide to Problem Selection in Carbohydrate Synthesis

“…The advances described in the sections above have contributed significantly to programmable methods for oligosaccharide synthesis analogous to those used in peptide synthesis. − To preface, the synthesis of linear peptides is largely automated, though with size limitations. Technologies such as native chemical ligation, however, assist in mitigating this issue. − Progress in the synthesis of peptides is the result of a remarkable understanding of the physiochemical properties governing their assembly.…”