Alkaloids from the Stem Bark of Micromelum falcatum

Abstract

Micromelum falcatum (LOUR.) TAN. (Rutaceae), traditionally used as Chinese folk medicine for curing infected wounds, odynolysis, and rheumatism, is widely distributed in Southeast Asia. The chemical constituents of M. falcatum had been previously investigated, and several coumarins, dihydrocinnamic acid derivatives, and two alkaloids 5,6-pyranoglycozoline and yuehchukene were obtained.1,2) The dimeric indole alkaloid yuehchukene was found to have potent anti-implantation activity.3) After further chemical investigation on the stem bark of M. falcatum, we report here the isolation of two new quinoldione alkaloids, methyl 2-(3-hydroxy-1-methyl-2,4-dioxo-1,2,3,4-tetrahydroquinolin-3-yl)acetate (1) and 3-hydroxy-1-methyl-3-(2-oxopropyl)-quinoline-2,4(1H,3H)-dione (2), two quinolinone alkaloids previously synthesized but first isolated as natural products, N-methylflindersine (3) 4,5) and 4-hydroxy-3-methoxy-1-methyl-2(1H)-quinolinone (4), 6) and the known N-methylswietenidine-B (5).7) All isolates were tested for toxicity towards brine shrimp larvae.

Biologically active quinoline and quinazoline alkaloids part II

“…Luo and co‐workers isolated N ‐methylswietenidine B ( 133 ), methyl 2‐(3‐hydroxy‐1‐methyl‐2,4‐dioxo‐1,2,3,4‐tetrahydroquinolin‐3‐yl)‐acetate ( 134 ) and 3‐hydroxy‐1‐methyl‐3‐(2‐oxopropyl)quinoline‐2,4(1H,3H)‐dione ( 135 ), N ‐methylflindersine ( 136 ), and 4‐hydroxy‐3‐methoxy‐1‐methyl‐2(1H)‐quinolinone ( 137 ) (Figure ) from Micromelum falcatum . Only 136 showed strong toxicity toward brine shrimp with an LD 50 value of 1.39 μg/mL; the LD 50 values of the other four compounds were more than 50 μg/mL.…”

“…102 N-Methyl-8methoxyflindersine (132) (Figure 17) also exhibited selective leishmanicidal activity against intracellular promastigotes (EC 50 : 14.3 g/mL). Acaricidal and insecticidal activity Luo and co-workers isolated N-methylswietenidine B (133), methyl 2-(3-hydroxy-1-methyl-2,4-dioxo-1,2,3,4tetrahydroquinolin-3-yl)-acetate (134) and 3-hydroxy-1-methyl-3-(2-oxopropyl)quinoline-2,4(1H,3H)-dione (135), Nmethylflindersine (136), and 4-hydroxy-3-methoxy-1-methyl-2(1H)-quinolinone (137)(Figure 17) from Micromelum falcatum 104. Only 136 showed strong toxicity toward brine shrimp with an LD 50 value of 1.39 g/mL; the LD 50 values of the other four compounds were more than 50 g/mL.…”

Rapid Identification of Coumarins from Micromelum falcatum by UPLC-HRMS/MS and Targeted Isolation of Three New Derivatives

“…Previous studies on M. falcatum have revealed the presence of several groups of secondary metabolites such as derivatives of dihydrocinnamic acid [5] and most importantly, alkaloids and coumarins. Specifically, numerous alkaloids belonging to the quinolone, quinoldione [6], indole and carbazole [7] groups have been isolated from the bark of the plant. In addition, several 6-and 8-prenylated derivatives of 7-oxygenated and specifically 7-methoxylated coumarins have been reported from the bark and the leaves of M. falcatum [5,[7][8][9].…”

“…The HPLC-DAD and UPLC-ESI(+)-HRMS and HRMS/MS profiling of different extracts of M. falcatum revealed useful spectroscopic and spectrometric features which enabled the detection of numerous coumarin derivatives and led to a targeted isolation thereof. In total, eight 7-methoxylated coumarins, among them the three new natural products microfalcrin (1), microcoumaririn (2), micromelosidester (3) and the known ones micromeloside A (4) [8], microminutin (5) [11], micromelin (6) [14], micromarin B (7) [15] and micromarin A (8) [15] were isolated and structurally elucidated. In addition, the inhibition of the NO synthase and the pro-inflammatory agent NF-κB by representative extracts and compounds was explored.…”

Coumarin Precursor from Micromelum integerrimum Leaves

“…Some of these plant extracts have also been used in traditional medicine for the treatment of fever, giddiness, dysentery, and arthritis [14,15]. In continuation of our study on the chemical constituents from Rutaceae plants, we wish to report herein the isolation and structure elucidation of a new compound from the leaves of M.integerrimum, namely integerriminol (1) along with 10 known coumarins (2-10) including micromelin (2) [2], dihydromicromelins A and B (3a and 3b) as a mixture (ratio 1:2) [3], acetyldihydromicromelin A (4) [3], scopoletin (5) [2], isoscopoletin (6) [16], citropten (7) [17], hopeyhopin (8) [18], 7hydroxy-8-(2',3'-dihydroxy-3'-methylbutyl)-coumarin (9) [19], tortuoside (10) [19], and a flavonoid, 5,7-dihydroxy-3,4',8trimethoxyflavone (11) [20] as shown in Figure 1. 13 C NMR spectral data and HMBC correlations of 1 (in CDCl 3 ).…”