Synthesis of C-glycosyl compounds of N-acetylneuraminic acid from d-gluconolactone

A general strategy towards the synthesis of C-glycosyl compounds of N-acetylneuraminic acid (Neu5Ac) has been developed and successfully applied to the synthesis of C-methyl and C-phenyl derivatives. The key strategic elements are (i) chain extension of a d-gluconolactone derivative as C 6-precursor with an allyl Grignard reagent as C 3-precursor having in 2 position the C-linked aglycon moiety, (ii) stereoselective C-4/C-5 erythro-diol formation, (iii) 6-exo-trig selective heterocyclization, and (iv) instalment of the 5-acetylamino and C-1 carboxylate functionalities. The efficiency and potential versatility of this approach was exemplified in the synthesis of C-methyl derivative 1 as target molecule. Graphic