N-Acetylneuraminic acid aldolase-catalyzed synthesis of acyclic nucleoside analogues carrying a 4-hydroxy-2-oxoacid moiety.

Abstract N -Acetylneuraminic acid aldolase (NeuAcA) (EC 4.1.3.3) is a pyruvate-dependent class I aldolase that catalyzes the reversible aldol cleavage of N -acetylneuraminic acid to form N -acetyl-D-mannosamine and pyruvate. The synthetic activity of this enzyme has been applied to the preparation of many sialic acid analogues. In this report, we demonstrate the ability of NeuAcA from Clostridium perfringens to use 2-oxoethyl substituted nucleobases as unusual acceptor substrates to perform aldol additions. In this way, novel acyclic nucleoside analogues bearing a further derivatizable 4-hydroxy-2-oxo butyrate skeleton were prepared in good yields. Graphical abstract Unlabelled Image Highlights • N -Acetylneuraminic acid aldolase was used to prepare acyclic nucleoside analogues. • 2-Oxoethyl substituted nucleobases were successfully used as acceptor substrates. • The enzyme tolerates both donor and acceptor substrate excess. • Our studies showed that products are stabilized by intramolecular hydrogen bonding. • The new products bear a further derivatizable 4-hydroxy-2-oxo butyrate skeleton. [ABSTRACT FROM AUTHOR]