Two chiral guanidines were evaluated as catalysts for the reaction of anthrone (1) with N-methylmaleimide (2). When guanidine 5 was used, the Michael adduct 4 was isolated as a major product. The best enantioselectivity (70% ee) was obtained when the reaction was carried out in THF at -20°C.
The synthetic studies for some known modulators of metabotropic glutamate receptors (mGluRs) such as (S)-αM4CPG, (1S,3R)-ACPD, L-CCG-I are described. Based on the structure of αM4CPG several new conformationally constrained analogues are design ed and synthesized. Among them APICA is a selective antagonist for group II mGluRs. Also, a new benzolactam-V8 analogue is found to have better isoform-selectivity for protein kine C family. Three different protocols for synthesizing benzolactam-VS analogues are developed to meet the requirement for delivering more analogues to test.
A bridged bicydic compound (7), the key intermediate for the synthesis of ( - )-huperzine A (1), was prepared by diastereos-elective Michael-aldol annulation of β-keto ester (4) catalyzed by chiral guanidine (2). A variety of chiral catalysts, substrates and reaction conditions were tested.
