Formal total syntheses of Myxothiazols by three different approaches starting from benzyloxyacetaldehyde

An efficient entry into the key intermediate for the total synthesis of myxothiazol A1 and related structures is described. We investigated three different approaches for building up the carbon framework starting from benzyloxyacetaldehyde and subjecting this to an aldol reaction, a titanium tetrachloride-mediated aldol reaction of a protected β-ketoester and a Barbier-type reaction using zinc or indium, respectively. The latter proved to be the longer (seven steps), but more efficient route, with 15% overall yield.