New approach to asymmetrically substituted methoxypyrazines, derivatives of wine flavors

An original synthetic route to asymmetrically substituted methoxypyrazine (MP) derivatives is described. The first step of the synthesis is achieved by condensation of 1,2-aminoalcohols with Boc-protected aliphatic aminoacids followed by cycloimine formation and aromatization via chlorination. Introduction of methoxy group was then achieved by alkoxy-de-halogenation. The use of primary or secondary aminopropanol enabled the direct and selective introduction of methyl group, in 5- or 6-position, which can be easily functionalized. Aromatization of diketopiperazine, prepared from l-valine and l-glutamic acid dimethyl ester, made possible a direct introduction of a functionalized alkyl chain. These reactions are also suitable for the synthesis of naturally-occurring MPs such as wine flavor components and biologically active substances.