Aglaxiflorin D from Aglaia abbriviata collected in Nghe An

Journal of Chemistry, Vol. 45 (6A), P. 362 - 366, 2007 Aglaxiflorin D from Aglaia abbriviata collected in Nghean Received 15 October 2007 Duong Ngoc Tu1,Duong Anh Tuan1 and Peter Proksch2 1Institute of Chemistry, Vietnamese Academic of Sciences and Technology 2Institut für Pharmazeutische Biologie und Biotechnologie, Heinrich-Heine-Universität Dässeldorf, Germany summary Phytochemical analysis of the leaves of Aglaia abbriviata collected in Nghean yielded a aglain derivative, which is structurally similar groups of compounds to rocaglamides. The structure of this compound Aglaxiflorin D (1) was elucidated through extensive 1D and 2D NMR spectroscopy and analysis of their mass spectrometric (ESI-MS) data. I - Introduction The genus Aglaia, which belongs to the Meliaceae family, has been described to yield a variety of different rocaglamide derivatives, which are responsible for strongly insecticidal activity. To date, more than fifty natural occurring rocaglamide derivatives were isolated from different Aglaia species collected mainly in Indonesia, China, Thailand and Vietnam. Aglains have been shown to be devoid of insecticidal activity against S.littoralis [Nugroho et al., 1997]. However, rocaglamides and aglains have been hypothesized to originate biosynthetically from common structurally related precursors that include cinnamic acid amides and flavonoids [Proksch et al., 2001](see Fig. 1). In this paper, we report on isolation and structure elucidation of a Aglain (Aglaxiflorin D) from Aglaia abbriviata. II - Experimental General experimental procedures. Optical rotations were recorded on a Perkin-Elmer-241 MC polarimeter. For HPLC analysis, samples 362 were injected into an HPLC system with a photodiode-array detector (Dionex, Munich, Germany). Routine detection was at 254 nm in aqueous MeOH. The separation column (125 x 4 mm, i.d.) was prefilled with C18 (Knauer, Berlin, Germany). Semi-preparative HPLC was performed on Merck-Hitachi Eurospher-100-C18, pump L-7100 and L-7400 UV detector. TLC was performed on TLC plates precoated with Si 60 F254 (Merck, Darmstadt, Germany). The compounds were detected from their UV absorbance and with ninhydrin spray reagent. 1D and 2D NMR spectra (chemical shifts in ppm) were recorded on Bruker DRX 500 spectrometers using standard Bruker software and DMSO-d6 was used as a solvent. ESI mass spectra were obtained on a Thermofinnigan LCQ DECA mass spectrometer coupled to an Agilent 1100 HPLC system equipped with a photodiode array detector. Plant materials Leaves of Aglaia abbriviata were collected from Con cuong, Nghean. They were dried in a drying room by utilizing dehumidifiers. The plant specimen was identified taxonomically and well kept at the storage department of the Institute of Chemistry, Vietnamese Academy of Sciences and Technology before commencing extraction work. These samples were then ground and extracted with n-hexane, dichloromethane, and methanol. The solvent was removed by a vacuum evaporator. Extraction and Isolation of Aglaxiflorin D (compound 1) The dried samples of Aglaia abbriviata leaves were extracted with n-hexane, ethylacetate and methanol successively. The ethylacetate extract (11 g) was chromatographed over a VLC column packed with Silica gel 60. Six fractions (F1-F6) were obtained. Fraction F6 was further separated by preparative TLC, resulting in four fractions (F6.1-F6.4). The fraction F6.1 was rechromatographed over Sephadex LH 20 column using 100% MeOH as mobile phase and yielded eleven fractions. Compound 1 (Aglaxiflorin D, 5 mg) was obtained by further separation from fraction F6.1.11 using preparative HPLC [Duong Ngoc Tu, 2005]. Fig. 1: Proposed joint biosynthetic origin of aglain derivatives V´ and rocaglamide derivatives VII [Proksch et al., 2001]. 363 III - Results and Discussion Compound 1 was obtained as a white amorphous residue from the leaves of Aglaia abbriviata, []20D-50.5 (c, 0.45, CHCl3); UV (MeOH) max 211.7 nm, 272.1nm. The ESI-MS positive mode showed the pseudomolecular ion peak at m/z 647.2 [M+H]+, and at m/z 669.3 [M+Na]+, respectively. The 1H NMR spectrum showed three methoxy groups at 3.72 (OCH3-6), 3.65 (OCH3-8) and 3.58 (OCH3-4´). In addition, three aromatic rings similar to those of Rocaglamide A (2) [Nugroho et al., 1997] were observed, i.e. two meta coupled aromatic protons at 5.96 ppm (d, 1.9, H-9) and 6.05 ppm (d, 1.9, H-7). The characteristic AA´BB´ system of a p-disubstituted benzene ring at 6.50 ppm (H3´/H5´, d, 8.8) and 7.31 ppm (H2´/H6´, d, 8.8) and the signals of a monosubstituted benzene ring at 6.85 ppm (H3´´/H4´´/H5´´, m) and 7.05 ppm (H2´´/H6´´, m) were likewise detected. The spectrum further 1 was identified as aglaxiflorin D, which was previously isolated from the leaves of Aglaia laxiflora collected in Taiwan [Luo et al., 2000]. O HO 15 14 OCH3 16 13 18 19 7 N H 20 H3CO 8 5a 5 11 9 1a 10 OH 4 2´´ O 3 3´´ 2 6´´ 4´´ 6´ 2´ 5´´ 5´ 3´ 4´ OCH3 Aglaxiflorin D (1) OCH3 OH OH H3CO 1 2 CON(CH3)2 5 3 O 2´´ 2´ 6´ exhibited signals at 4.22 ppm (d, 9.5) and 4.34 ppm (d, 9.5) typical of H-2 and H-3 in rocaglamide congeners. However, H-10 4´ 5´´ OCH3 resonated as a singlet at 4.48 ppm, this particular proton signal is indicative of the aglains which differentiate them from the rocaglamide family. Furthermore, the signals of a 2-methylbutyric amide and a 2-aminopyrrolidine ring reminiscent of the one reported for odorinol were also observed (see table 1), suggesting that part of the odorinol structure could be linked through an amide function to an acid moiety of the rocaglamide type instead of the NMe2 group [Dumontet et al., 1996]. The odorinol part of the structure was confirmed from its 1H-1H COSY spectrum (see Table 1 and Fig. 2), and was assigned accordingly: 0.80 (3H, t, J = 7.5 Hz, H-21), 1.09 (3H, s), 2.10 (1H, m, H-14A), 1.90 (1H, m, H-14B), 1.85 (1H, m, H-15A), 1.71 (1H,m, H-15B), 3.41 (1H, m, H-16A), 3.19 (1H, m, H-16B). Furthermore, a signal at 6.76 ppm (dd, J = 4.35 Hz, 11.95 Hz) was assigned to H-13, residing between the two nitrogen atoms of the pyrrimidine ring. Based on the 1H NMR, 1H-1H COSY spectra (see Table 1, Fig. 2) compound 364 Rocaglamide A (2) Acknowledgement: The authors acknowledge Dr. Luu Tham Muu and Bsc. Nguyen Kim Dao for collecting the plant samples as well as for the taxonomical identification. We would like to thank the DAAD for a scholarship and the Vietnamese Academy of Science and Technology (VAST) for financial support. Refferences 1. V. Dumontet, O. Thoison, O. R. Omobuwajo, M. T. Martin, G. Perromat, A. Chiaroni, C. Riche, M. Pais, T. Sevenet. Tetrahedron, 52, 6931 (1996). 2. Duong Ngoc Tu, Inaugural-Disertation zur Erlangung des Doktorgrades der Mathematisch-Naturwissenchaftlichen Fakultät der Heinrich-Heine-Universität Düsseldorf, 2005. Table 1: 1H NMR and 1H-1H COSY of Aglaxiflorin D (in MeOD) 1H-NMR Aglaxiflorin D 3 4.34( d, 9.5 Hz) 4 4.22 (d, 9.5 Hz) 7 6.05 (d, 1.9 Hz) 9 5.96 (d,1.9 Hz) 2´ 7.31(d, 8.8 Hz) 3´ 6.50 (d, 8.8 Hz) 5´ 6.50 (d, 8.8 Hz) 6´ 7.31 (d, 8.8 Hz) 2´´ 7.05 (m) a COSY 4.56 (d, 9.0) 4 4.04 (d, 9.0) 3 6.08 (d, 0.8) 6.05 (d, 0.8) 7.38 (d, 8.4) 3´ 6.65 (d, 8.4) 2´ 6.65 (d, 8.4) 6´ 7.38 (d, 8.4) 5´ 7.19 (m) 3´´ 3´´ 6.85(m) 4´´ 6.85 (m) 5´´ 6.84 (m) 6´´ 7.05 (m) OMe-6 3.72 (s) OMe-8 3.65 (s) OMe-4´ 3.58 (s) 10 4.48 (s) 13 6.76 (m) 14 B: 1.90 (m) A: 2.10 (m) 15 B: 1.71 (m) A: 1.85 (m) 16 B: 3.19 (m) A: 3.41 (m) 20 A: 1.38 (m) B: 1.65 (m) 21 0.80 (t, 7.5) 22 1.09 (s) 7.00 (m) 7.00 (m) 7.00 (m) 7.19 (m) 3.78 (s) 3.71 (s) 3.69 (s) 4.83 (s) 6.38 (m) B: 1.96 (m) A: 2.05 (m) B: 1.74 (m) A: 1.91 (m) B: 3.20 (m) A: 3.61 (m) B: 1.42 (m) A: 1.62 (m) 0.74 (t, 7.3) 1.24 (s) 2´´,4´´ 3´´,5´´ 4´´,6´´ 5´´ 14 13,15 14 21 20 a:[Luo et al., 2000] (measured in MeOD). 365 15A 15B 14A 14B 20B 22 21 20A (ppm) 15 14 O HO 22 20B/21 20A/21 0.8 7 8 H3CO OCH3 6 OH N 5a 5 11 13 18 19 H 20 21 1.2 20A/20B 1.6 9 1a 10 OH 4 H O 3 2 6´´ 6´ 2´ O 2´´ 3´´ 4´´ 5´´ 5´ 3´ 4´ 14B/15B 2.0 OCH3 14A/14B 2.4 (ppm) 2.4 2.0 1.6 1.2 0.8 Fig. 2: 1H-1H COSY correlations of Aglaxiflorin D in MeOD (upfield region) 3. 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