Solid-phase synthesis of pyridones and pyridopyrazines as peptidomimetic scaffolds

[GRAPHICS] We report the syntheses of peptidomimetic opioids containing the core struc ture N-alkyl-2-alkyl-2,3-dihydro-4-pyridone. By employing imines bound on a solid support and the Danishefsky diene, this [4 + 2] cyclocondensation re action facilitates the synthesis of novel complex heterocycles. The central reaction is carried out under mild conditions and employs readily availabl e building blocks. In this study we demonstrate the suitability of alkyl-2- alkyl 2,3-dihydro-4-pyridones as a central scaffold for peptidomimetics and establish the scope of this [4 + 2] cyclocondensation reaction with imino acids on a solid phase, We also combine the synthesis of diketopiperazines with the [4 + 2] cyclocondensation reaction to form a 9,9a-dihydro-2H-pyrid o-[1,2a]-pyrazine-3,8(1,4-dialkyl)dione, a bicyclic molecule containing a p yridopyrazine core structure.