Formal synthesis of (−)-N-acetylneuraminic acid (Neu5Ac) via desymmetrization by ring-closing metathesis

A formal total synthesis of (−)-N-acetylneuraminic acid (Neu5Ac), the most naturally abundant sialic acid, has been accomplished using a rigid 6,8-dioxabicyclo[3.2.1]octane template for stereoselective introduction of all oxygen and nitrogen functionality. The template was obtained via a novel ketalization/ring-closing metathesis bond construction strategy, taking advantage of an advanced intermediate in our KDN synthesis to complete the efficient assembly of Neu5Ac.