Solid-phase synthesis of pyridones and pyridopyrazines as peptidomimetic scaffolds.
[formula: see text] We report the syntheses of peptidomimetic opioids containing the core structure 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 reaction facilitates the synthesis of novel complex heterocycles. The central reaction is carried out under mild conditions and employs readily available building blocks. In this study we demonstrate the suitability of N-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-pyrido-[1,2a]- pyrazine-3,8(1,4-dialkyl)dione, a bicyclic molecule containing a pyridopyrazine core structure.
Creighton
C J
CJ
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093-0343, USA.
Zapf
C W
CW
Bu
J H
JH
Goodman
M
M
D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D011719:Pyrazines / Q000737:chemistry*; D011728:Pyridones / Q000138:chemical synthesis*
D010455:Peptides; D011719:Pyrazines; D011728:Pyridones