Collective Synthesis and PCSK9 Inhibitory Activities of Pavine and Isopavine Alkaloids

An efficient approach for the synthesis of pavine and isopavine alkaloids through photoredox-catalyzed intramolecular cyclization is disclosed, which features low catalyst dosage and good functional group compatibility. A total of 18 natural products, including 10 pavine and 8 isopavine alkaloids as well as 20 analogs, have been successfully synthesized by this protocol. A plausible reaction mechanism was also proposed. Moreover, preliminary PCSK9 inhibitory activities of these compounds were evaluated. Compound 1’f exhibited the most potent PCSK9 inhibitory activity with the IC50 value of 161 nM, superior to the positive control berberine.