Aspongopyrimidine A, a N -Peralkylated Histidine Zwitterion from Aspongopus chinensis against Alzheimer's Disease Targeting MAPRE3.

Aspongopyrimidine A ( 1 ), a hexa-1,3-diene-histidine-hexanoic acid adduct featuring a 4,5-dihydro-2 H -10λ 4 -imidazo[5,1- f ]pyrrolo[2,1- b ]pyrimidine motif, was isolated from the insect Aspongopus chinensis . The structure was clarified by spectroscopic and computational methods and X-ray diffraction. Peralkylation of N -atoms in histidine by two C6 units makes 1 an inner salt with a 5/6/5 tricyclic system. Biological evaluation found that 1 exerts activity against Alzheimer's disease targeting MAPRE3 through a chemical proteomics approach. This study revealed unusual modifications of amino acids as the fundamental units of protein.