Versatile synthetic route to carbocyclic N-Acetylneuraminic acid and its derivatives

Abstract

Sialic acid (N-acetylneuraminic acid) is a carbohydrate that possess a nine carbon backbone, and it is often found at the termini of glycoconjugates in biological systems. Because of this prominence many syntheses have reported routes to sialic acid and many of its derivatives. Most of these compounds retain the endocyclic oxygen atom that becomes part of the ketal glycosidic linkage that joins sialic acid to the penultimate residue in the glycoconjugate. With respect to carba-sialic acid (replacement of the ring oxygen atom with a methylene group) a single synthesis has been reported (Ogawa et al. (Carbohydr. Res., 1995, 269, 53–78) in 30 steps and 0.5% yield. The current report details a robust synthesis of 6a-carba-α-D-sialic acid that involves 18 steps and give a 5% yield using D-quinic acid as the starting material.