Chemoenzymatic Synthesis of Sialic Acid Derivatives Using Immobilized N‐Acetylneuraminate Lyase in a Continuous Flow Reactor

Abstract

The synthesis of N‐acetylneuraminic acid (Neu5Ac) derivatives is drawing more and more attention in glycobiology research because of the important role of sialic acids in e. g. cancer, bacterial, and healthy cells. Chemical preparation of these carbohydrates typically relies on multistep synthetic procedures leading to low overall yields. Herein we report a continuous flow process involving N‐acetylneuraminate lyase (NAL) immobilized on Immobead 150P (Immobead‐NAL) to prepare Neu5Ac derivatives. Batch experiments with Immobead‐NAL showed equal activity as the native enzyme. Moreover, by using a fivefold excess of either N‐acetyl‐D‐mannosamine (ManNAc) or pyruvate the conversion and isolated yield of Neu5Ac were significantly improved. To further increase the efficiency of the process, a flow setup was designed providing a chemoenzymatic entry into a series of N‐functionalized Neu5Ac derivatives in conversions of 48–82%, and showing excellent stability over 1 week of continuous use.

Metabolic Glycoengineering in hMSC-TERT as a Model for Skeletal Precursors by Using Modified Azide/Alkyne Monosaccharides

“…The alkyne mannose was synthesized according to the literature [ 57 ], with slight modification. Briefly, 2-amino-2-deoxy- d -manno-pyranose hydrochloride (238 mg, 1.10 mmol, 1.00 eq.)…”

Biocatalysis making waves in organic chemistry

“…Pyruvate dependent aldolases play a central role in the synthesis of ulosonic acids and sialic acids which has recently been reviewed 35,39,80,81,101,102 and a longstanding industrial example illustrates the power of the approach (Scheme 8), dating back to the first wave of biocatalysis. [103][104][105][106] Class II pyruvate dependent aldolases are part of the lignin and polycyclic aromatic compound degrading enzymes. As degrading enzymes they are more flexible for their substrates and therefore in the focus of attention.…”

Characterization of Sialic Acid-Binding Immunoglobulin-Type Lectins in Fish Reveals Teleost-Specific Structures and Expression Patterns

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