Isolation, Identification, and Total Synthesis of Pyranoquinolinone Alkaloids from <i>Conchocarpus mastigophorus</i> Kallunki (Rutaceae)

In this study, the phytochemical profile of <i>Conchocarpus mastigophorus</i> was investigated, leading to the isolation of four pyranoquinolinone alkaloids, including huajiaosimuline (<b>1</b>) and three new compounds: 3'-acetoxy-4'-hydroxyzanthosimuline (<b>2</b>), epoxyzanthosimuline (<b>3</b>), and mastigophorine (<b>4</b>). All new compounds possess two chiral centers and exist as a 1:1 mixture of epimers, differing in the configuration of a chiral center at the pyran ring. The absolute configurations of the epimers <b>2</b> and <b>3</b> were determined by data comparison with identical synthetic compounds, revealing mixtures of (2<i>S</i>,3'<i>R</i>)<i>-</i> and (2<i>R</i>,3'<i>R</i>)-configured epimers in both cases. By employing Sharpless asymmetric dihydroxylation and Shi epoxidation as key stereoselective steps, stereocontrol at C3 was achieved in the synthesis of compounds <b>2</b> and <b>3</b>, respectively. Our synthesis approach provided 3<i>'R</i>- and 3<i>'S</i>-configured <b>2</b> in three steps (41-46% overall yield, 95% dr) and 3<i>'R</i>-configured <b>3</b> in 2 steps (61% overall yield, 90% dr) from 4-hydroxy-1-methyl-2(1<i>H</i>)-quinolinone and citral.