The lupane-type triterpenoids are endowed with a wide range of biological activities such as antiviral, anti-inflammatory and anticancer activity. We describe here its potential application in Alzheimer's disease (AD) treatment as an inhibitor of PS1/BACE1 interaction. 3-a-Akebonoic acid, which emanated from a high throughput screening (HTS), was discovered to interfere with P S 1/BACE 1 interaction and reduce amyloid β-protein (Aβ) production. In view of the limited source, we instead used naturally rich betulinic acid (compound 2) as starting material for lead optimization and a focused library of its derivatives was constructed to gain a better understanding of the structure activity relationship (SAR) of triterpenoid-type inhibitor of PS1/BACE1 interaction. Compound 22 was finally chosen as the most potent PS 1/BACE 1 interaction inhibitor, which reduced Aβgeneration effectively.
A novel copper-catalyzed dual oxidative benzylic C–H aminations of methylarenes with 2-aminobenzoketones in the presence of ammonium acetate was developed. This reaction represents a new avenue for 2-arylquinazolines with good yields. A key intermediate was detected and the kinetics isotope effect(KIE) indicated that C–H bond cleavage was the rate-determining step.