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

Abstract

In this study, the phytochemical profile of Conchocarpus mastigophorus was investigated, leading to the isolation of four pyranoquinolinone alkaloids, including huajiaosimuline (1) and three new compounds: 3′-acetoxy-4′-hydroxyzanthosimuline (2), epoxyzanthosimuline (3), and mastigophorine (4). 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 2 and 3 were determined by data comparison with identical synthetic compounds, revealing mixtures of (2S,3'R)- and (2R,3'R)-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 2 and 3, respectively. Our synthesis approach provided 3'R- and 3'S-configured 2 in three steps (41–46% overall yield, 95% dr) and 3'R-configured 3 in 2 steps (61% overall yield, 90% dr) from 4-hydroxy-1-methyl-2(1H)-quinolinone and citral.