Chemoenzymatic synthesis of CMP-N-acetyl-7-fluoro-7-deoxy-neuraminic acid.
7-Fluoro sialic acid was prepared and activated as cytidine monophosphate (CMP) ester. The synthesis started with d-glucose, which was efficiently converted into N-acetyl-4-fluoro-4-deoxy-d-mannosamine. Aldolase catalyzed transformation yielded the corresponding fluorinated sialic acid which was activated as CMP ester using three different synthetases in the presence as well as in the absence of pyrophosphatase which possesses inhibitory properties. Finally, conditions were optimized to perform a one-pot reaction starting from fluorinated mannosamine, which yielded the 7-fluoro-7-deoxy-CMP-sialic acid by incubation with three enzymes.
Hartlieb
Sina
S
Institut für Organische Chemie und Zentrum für Biomolekulare Wirkstoffchemie (BMWZ), Gottfried Wilhelm Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover, Germany.
Günzel
Almut
A
Gerardy-Schahn
Rita
R
Münster-Kühnel
Anja K
AK
Kirschning
Andreas
A
Dräger
Gerald
G
D003569:Cytidine Monophosphate N-Acetylneuraminic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D005634:Fructose-Bisphosphate Aldolase / Q000378:metabolism; D000216:N-Acylneuraminate Cytidylyltransferase / Q000378:metabolism
C532042:CMP-N-acetyl-7-fluoro-7-deoxyneuraminic acid; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D000216:N-Acylneuraminate Cytidylyltransferase; D005634:Fructose-Bisphosphate Aldolase