抄録
The genus Melicope (family Rutaceae) comprises about 230 species and occurs in the tropics and the subtropics ranging from Madagascar to the Hawaiian Islands. M. denhamii (Seem.) T.G. Hartley is a shurub or tree that grows to 0.5-25 m high and distributes among Indonesia, Malaysia and the Philippines. No phytochemical studies on this plant have yet been achieved. In the current study, we have investigated the chemical constituents in the leaves and isolated eight novel quinolinone alkaloids, melicodenine A-H (1-8), and two new phenyl propanoids, melicodins A and B (10, 11), as well as a new coumarinolignoid, melicodin C (9), by means of repeated column chromatography using silica gel, Sephadex LH-20 and semi-preparative HPLC. Their structures were established by extensive spectrometric and spectroscopic analyses including LC-IT-TOFMS, 1D- and 2D-NMR techniques, CD spectra, etc. Melicodenine A (1) is apparently formed from two molecules of N-methylflindersine (13) through Diels-Alder cycloaddition, while melicodenines B-H (2-8) may be formed from each one molecule of 13 and the counterpart assignable to an acetophenone (15), a phenylpropanoid (10) or a furocoumarin through Diels-Alder or [2+2] cycloaddition. In addition, melicodin C (9) is a potential [2+2] cycloadduct derived from 10 and 17. Thus, M. denhamii produces varieties of N-methylflindersine-originated complex compounds via possible biogenetic pathways illustrated in Scheme 1. Compounds 1-9, 12, and 13 were tested for the anti-proliferative activity against human colon cancer DLD-1 cells. Melicodenine H (8) induced apoptosis and showed the most potent activity with the IC_<50> value of 9.4±0.3
