Gram scale de novo synthesis of 2,4-diacetamido-2,4,6-trideoxy-d-galactose

In contrast to the infection with Gram-negative bacteria, the precise mechanism of infection with their Gram-positive counterparts is still poorly understood. It has been established, that teichoic and lipoteichoic acids play an important role in host–pathogen interaction. The bacterium Streptococcus pneumoniae is one of the severe life-threatening Gram-positive pathogens and elucidation of the structure of its lipoteichoic acid revealed 2,4-diacetamido-2,4,6-trideoxy-d-galactose as a main component of the cell wall glycopolymer. Our approach toward this carbohydrate used an l-threonine derived aldehyde as starting material following the Garner protocol, which was subjected to a nitro aldol reaction with 2-nitroacetaldehyde diethylacetal to generate the galacto configurated carbon backbone. Subsequent reduction of the nitro group and peracetylation of the molecule resulted in a fully and orthogonally protected derivative, which was deprotected by a single step in pure deionized water at elevated temperatures.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► An l-threonine derived aldehyde was used as chiral starting material. ► The carbon backbone of the target sugar was generated via a nitro aldol reaction. ► Final global deprotection was achieved in boiling deionized water. ► All the reactions were performed on a gram scale.