A General Method for the Divergent Synthesis of C‐9 Functionalised Sialic Acid Derivatives

Abstract

Sialic acids, a ubiquitous family of sugars shown to be involved in numerous biologically important processes, exhibit remarkable structural diversity in nature. Access to these derivatives by chemical and enzymatic means is a major bottle neck in understanding the role played by each particular modification. As part of a program to study such roles and determine the substrate specificity of novel sialic acid aldolases, a general and robust synthetic protocol was devised to gain access to all naturally occurring C‐9 functionalised N‐acetylneuraminic acid derivatives including esters. These derivatives were synthesised in 11 linear steps from a common advanced intermediate, which allowed for divergent modification at the C‐9 position. Four substitutions were installed in this study: O‐acetyl, O‐lactyl, O‐SO3, O‐PO3. This synthetic pathway includes both an effective way to benzylate neuraminic acid derivatives, as well as a working methodology towards unnatural β‐linked neuraminic acid glycosides.