Novel Approaches Toward the Synthesis of Pseudaminic Acid

Pseudaminic acid is a carbohydrate glycoside which is found on post-translationally glycosylated bacterial flagella. Disturbance of the biosynthetic pathway for this sugar nullifies the pathogenicity of the bacteria A. caviae, H. pylori & C. jejuni. In order to explore this possibility, attempts were made to develop a novel synthetic route.

Parallel to efforts to synthesis the side chain of pseudaminic acid, L-allo-threonine, N-chiral imines derived from cheap and readily available (2S)-ethyl lactate were prepared and subjected to Lewis acid-mediated trimethylsilylcyanide additions as part of new methodology for robust and facile asymmetric Strecker reactions. 2,3-anti¬-β-Hydroxy-α-aminonitriles were prepared in excellent yield (77%, 4 steps) and good diastereoselectivity (90 : 10).

L-allo-threonine was accessed and further functionalised to Garner-like cyclic aldehydes which were used as substrates for a doubly diastereoselective nitroaldol reaction to construct the carbon chain of pseudaminic acid. These reactions proceeded with mild selectivity and conversion. Models for the addition to both Garner aldehydes and N-chiral imines were discussed in detail.