1. Chemoenzymatic Synthesis of Sialic Acid Derivatives Using Immobilized Acetylneuraminate Lyase in a Continuous Flow Reactor
- Author
-
Bloemendal, Victor R. L. J., Moons, Sam J., Heming, Jurriaan J. A., Chayoua, Mohamed, Niesink, Olaf, van Hest, Jan C. M., Boltje, Thomas J., Rutjes, Floris P. J. T., and Bio-Organic Chemistry
- Subjects
Immobilized enzyme ,flow chemistry ,Synthetic Organic Chemistry ,SDG 3 – Goede gezondheid en welzijn ,010402 general chemistry ,01 natural sciences ,chemistry.chemical_compound ,SDG 3 - Good Health and Well-being ,enzyme immobilization ,chemistry.chemical_classification ,010405 organic chemistry ,Communication ,N-acetylneuraminate lyase ,General Chemistry ,Flow chemistry ,Lyase ,Combinatorial chemistry ,Communications ,0104 chemical sciences ,Sialic acid ,Enzyme ,chemistry ,Yield (chemistry) ,N-acetylneuraminic acid ,N-Acetylneuraminic acid - 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. (Figure presented.).
- Published
- 2019
- Full Text
- View/download PDF