A versatile de novo synthesis of legionaminic acid and 4-epi-legionaminic acid starting from d-serine

Legionaminic acid and 4-epi-legionaminic acid are 5,7-diacetamido nonulosonic acids and are assumed to play a crucial role in the virulence of Legionella pneumophila, the causative agent of Legionnaires’ disease. Moreover, they are ideal target motifs for the development of vaccines and pathogen detection. Herein, we present a versatile de novo synthesis of legionaminic acid and 4-epi-legionaminic acid. Starting from simple d-serine, the C9-backbone is built up by two CC-bond formation reactions. First, the protected d-serine motif is elongated utilizing a highly stereoselective nitroaldol reaction to give a C6-precursor of desired d-rhamno configuration. Second, an indium-mediated allylation is employed to further elongate the carbon backbone and introduce a masked α-keto acid function. [Display omitted] •De novo synthesis of legionaminic acid and 4-epi-legionaminic acid starting from simple and commercially available d-serine.•Highly stereoselective nitroaldol reaction gives a C6-precursor of d-rhamno configuration.•Indium-mediated allylation allows for further elongation introducing a masked α-keto acid function.•This method gives access to install diversely tailored N-acylation patterns.