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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.