This article was downloaded by: [Memorial University of Newfoundland] On: 01 August 2014, At: 01:11 Publisher: Taylor & Francis Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK Natural Product Research: Formerly Natural Product Letters Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/gnpl20 One new and several minor diarylheptanoids from Amomum muricarpum a a b Phan Minh Giang , Phan Tong Son , Katsuyoshi Matsunami & Hideaki Otsuka b a Faculty of Chemistry, College of Natural Science, Vietnam National University , Hanoi, 19 Le Thanh Tong Street, Hanoi , Vietnam b Graduate School of Biomedical Sciences, Hiroshima University , 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553 , Japan Published online: 23 Aug 2011 To cite this article: Phan Minh Giang , Phan Tong Son , Katsuyoshi Matsunami & Hideaki Otsuka (2012) One new and several minor diarylheptanoids from Amomum muricarpum , Natural Product Research: Formerly Natural Product Letters, 26:13, 1195-1200, DOI: 10.1080/14786419.2010.545775 To link to this article: http://dx.doi.org/10.1080/14786419.2010.545775 PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content This article may be used for research, teaching, and private study purposes Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden Terms & Downloaded by [Memorial University of Newfoundland] at 01:11 01 August 2014 Conditions of access and use can be found at http://www.tandfonline.com/page/termsand-conditions Natural Product Research Vol 26, No 13, July 2012, 1195–1200 One new and several minor diarylheptanoids from Amomum muricarpum Downloaded by [Memorial University of Newfoundland] at 01:11 01 August 2014 Phan Minh Gianga*, Phan Tong Sona, Katsuyoshi Matsunamib and Hideaki Otsukab a Faculty of Chemistry, College of Natural Science, Vietnam National University, Hanoi, 19 Le Thanh Tong Street, Hanoi, Vietnam; bGraduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan (Received 30 June 2010; final version received December 2010) A new natural diarylheptanoid, designated muricarpin, together with four diarylheptanoids were isolated from the rhizomes of Amomum muricarpum Elmer (Zingiberaceae) growing in Vietnam Three known compounds, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate, 1-(40 -hydroxyphenyl)-7(300 ,400 -dihydroxyphenyl)heptan-3-yl acetate and 1-(30 ,40 -dihydroxyphenyl)7-(400 -hydroxyphenyl)-heptan-3-one were isolated for the first time from the genus Amomum, meanwhile (5R)-5-hydroxy-1,7-bis(4-hydroxyphenyl)heptan-3-one was found for the first time in plants Their structures were determined using spectroscopic analyses Keywords: Amomum muricarpin muricarpum; Zingiberaceae; diarylheptanoid; Introduction Within the family Zingiberaceae a number of diarylheptanoids are known to be biosynthesised by plants of the genera Alpinia (Ali, Tezuka, Awale, Banskota, & Kadota, 2001), Curcuma (Park & Kim, 2002) and Zingiber (Kikuzaki, Kobayashi, & Nakatani, 1991) Regarding the genus Amomum, very few reports were published on the occurrence of diarylheptanoids (Giang, Son, Matsunami, & Otsuka, 2006; Kikuzaki, Kawai, & Nakatani, 2001; Moon, Cho, & Lee, 2005) Amomum muricarpum Elmer is a plant of 2–3 m height which is distributed in China, Philippines and Vietnam (Flora of China, 2010, http://www.efloras.org) The rhizomes of A muricarpum originating in Vietnam have been shown to be a source of diarylheptanoids and our previous paper (Giang et al., 2006) reported the isolation of two new diarylheptanoids, muricarpone A and muricarpone B, together with 1,7-bis(30 ,40 -dihydroxyphenyl)-4-hepten-3-one, 1-(30 ,40 -dihydroxyphenyl)-7(400 -hydroxyphenyl)-4-hepten-3-one, and 1,7-bis(p-hydroxyphenyl)-4-hepten-3-one The diarylheptanoid constituents from the Amomum species are of our interest and further investigation on the minor constituents of A muricarpum led to the isolation of a new diarylheptanoid, designated muricarpin (1), together with *Corresponding author Email: phanminhgiang@yahoo.com ISSN 1478–6419 print/ISSN 1478–6427 online ß 2012 Taylor & Francis http://dx.doi.org/10.1080/14786419.2010.545775 http://www.tandfonline.com 1196 P.M Giang et al OH OH OH R2 O OH HO AcO OH R1 = OH R2 = H R1 = H R2 = OH R = OH R=H R R1 OH Downloaded by [Memorial University of Newfoundland] at 01:11 01 August 2014 O OH Figure HMBC correlations of and structures of compounds 1–5 three known compounds 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (2), 1-(40 -hydroxyphenyl)-7-(300 ,400 -dihydroxyphenyl)heptan-3-yl acetate (3) and 1-(30 ,40 dihydroxyphenyl)-7-(400 -hydroxyphenyl)-heptan-3-one (4) (Figure 1) 5-Hydroxy-1,7bis(4-hydroxyphenyl)-heptan-3-one was previously synthesised as a racemic mixture (Bratt & Sunnerheim, 1999); its 5S enantiomer (platyphyllonol) was isolated from Betula platyphylla Sukatch var japonica Hara (Terazawa, Koga, Okuyama, & Miyake, 1973) or semi-synthesised (Park et al., 2010); therefore compound (5R form) was isolated for the first time from plants Results and discussion The dried rhizomes of A muricarpum were extracted with MeOH and the resulting MeOH extract was sequentially fractionated using solvents of increasing polarities to give n-hexane-, CH2Cl2-, EtOAc- and 1-BuOH-soluble fractions The diarylheptanoids were isolated from the CH2Cl2- and EtOAc-soluble fractions by a sequential fractionation using silica gel and octadecyl silica (ODS) gel open-column chromatography (CC) and purification by repeated preparative reversed-phase HPLC Compound was isolated as a syrup Its molecular formula was deduced to be C19H22O4 ([M–H]– m/z 313.1404) by negative-ion HR-FABMS The IR spectrum showed the presence of hydroxyl (3345 cm–1), ketone (1698 cm–1) and aromatic ring (1609, 1514 and 1445 cm–1) absorptions The 1H and 13C NMR spectroscopic data of showed the presence of a diaryl-3-heptanone (C 213.6, C-3) (Kiuchi, Shibuya, & Sankawa, 1982; Itokawa, Morita, Midorikawa, Aiyama, & Morita, 1985) Two aromatic moieties were determined to be 3,4-dihydroxyphenyl [H 6.64 (1H, d, J ¼ 8.0 Hz), 6.58 (1H, d, J ¼ 2.0 Hz) and 6.45 (1H, dd, J ¼ 8.0 Hz, 2.0 Hz)] and 4-hydroxyphenyl [H 6.97 (2H, d, J ¼ 8.8 Hz) and 6.67 (2H, d, J ¼ 8.8 Hz)] on the basis of 1H NMR coupling patterns HMBC correlations between the methylene protons at H 2.67 (H2-2) and C-100 (C 133.3), between H-20 /H-60 (H 6.97) and C-1 (C 30.2), between H2-7 (H 2.39) and C-100 (C 135.3), C-200 (C 116.6), and C-600 (C 120.7), between H-200 (H 6.58) and C-7 (C 35.9) and between H-600 (H 6.45) and C-7 indicated the locations of the 4-hydroxyphenyl and 3,4-dihydroxyphenyl rings at C-1 and C-7, respectively Thus the structure of was determined to be 1-(40 -hydroxyphenyl)-7-(300 ,400 -dihydroxyphenyl)-heptan-3-one, which was named muricarpin Downloaded by [Memorial University of Newfoundland] at 01:11 01 August 2014 Natural Product Research 1197 Compounds 2–4 were found in MEGxp Catalog (Collection of pure natural products from plants) of AnalytiCon Discovery GmbH under code numbers NP-003624, NP-012941 and NP-012940, respectively (AnalytiCon Discovery GmbH, 2010, http://www.ac-discovery.com) However, no references and data on these compounds were available and therefore the physico-chemical and spectroscopic data of 2–4 were reported in this article Compound was isolated as a syrup, []25 D ỵ51.8 The IR spectrum showed the presence of hydroxyl (3400 cm–1), ketone (1699 cm–1) and aromatic ring (1611, 1513 and 1450 cm–1) absorptions The 1H NMR spectroscopic data of showed the planar structure of as 5-hydroxy-1,7-bis(4-hydroxyphenyl)-heptan-3-one Recently, its 5S enantiomer platyphyllonol, which possessed a negative optical rotation ([]25 D –1.8), was semi-synthesised from its glucoside platyphylloside (Park et al., 2010) Since the H NMR of was in good agreement with that of platyphyllonol its positive optical rotation decided the absolute stereochemistry 5R of the hydroxyl group at C-5 of In conclusion, this study and the previous one (Giang et al., 2006) showed that linear diarylheptanoids are the main type of secondary metabolites of A muricarpum The structures of these diarylheptanoids appeared to be biogenetically-related; while the aryl moieties were 4-hydroxyphenyl or 3,4-dihydroxyphenyl groups the heptane chain contained 3-oxygenated or 3,5-dioxygenated pattern Experimental 3.1 General experimental procedures Optical rotation was measured on a JASCO P-1030 digital polarimeter FT-IR spectra were recorded on a Horiba FT-710 spectrophotometer 1H (400 MHz) and 13 C NMR (100 MHz) spectra were recorded using a JEOL JNM- 400 NMR spectrometer with TMS as an internal standard Negative-ion HR-FABMS spectra were measured on a JEOL SX-102 mass spectrometer with PEG-400 as a calibration matrix HPLC was carried out with a JASCO PU-1580 pump and an UV-2075 Plus detector (set at 254 nm) on ODS (YMC, Japan) analytical (150 Â 4.6 mm i.d.) and preparative (150 Â 20 mm i.d.) columns at the corresponding flow rates of 0.5 and ml/min Silica gel 60 (0.063–0.200 mm, Merck, Germany) and ODS gel (YMC, Japan) were used for open-column chromatography TLC was carried out on glass TLC plates (silica gel 60 F254, Merck, Germany) and detected by spraying with 10% H2SO4 in 50% EtOH, followed by heating on a hot plate at 200oC 3.2 Plant material The rhizomes of A muricarpum were collected from Tam Dao, province Vinh Phuc, Vietnam, and identified by Mr Nguyen Quoc Binh, a botanical taxonomist of the Institute of Ecology and Biological Resources, Vietnam Academy of Science and Technology, Hanoi, Vietnam, in October 2003 A voucher specimen (no VN 1199) has been deposited at the Institute of Ecology and Biological Resources 3.3 Extraction and isolation The fresh rhizomes of A muricarpum (7.3 kg) were oven-dried at 40oC and the dried material (0.84 kg) was powdered and then extracted with MeOH at room Downloaded by [Memorial University of Newfoundland] at 01:11 01 August 2014 1198 P.M Giang et al temperature (three times, each time for three days) After filtration and concentration under reduced pressure, the resulting MeOH extract (80 g) was successively partitioned between H2O and n-hexane, CH2Cl2, ethyl acetate and 1-BuOH The CH2Cl2-soluble fraction (12.5 g) was chromatographed on silica gel using a gradient of CHCl3 and CHCl3/MeOH (9 : 1) to give four fractions on the basis of TLC analyses Fraction (3.9 g) was further subjected to silica gel CC using n-hexane/ acetone : to give four subfractions Subfraction (0.83 g) was purified by reversed-phase HPLC using MeOH/H2O (1 : 1) to afford (12.8 mg) The EtOAcsoluble fraction (25.7 g) was subjected to silica gel CC and eluted under gradient conditions with CHCl3 and CHCl3/MeOH (4 : 1, : 2, : and : 4) to afford six fractions Fraction (1.0 g) was purified by reversed-phase HPLC using MeOH/H2O (1 : 1), yielding (1.1 mg) Fraction (21.7 g) was chromatographed on a silica gel column with n-hexane/acetone (gradient : and : 1) to afford six subfractions Subfraction (1.0 g) was further purified by reversed-phase HPLC using MeOH/H2O (1 : 1) to yield (10.8 mg) and (7.6 mg) Subfraction (2.4 g) was sequentially chromatographed on an ODS column eluting with a gradient of MeOH/H2O (3 : and : 3) and reversed-phase HPLC using MeOH/H2O (1 : 1) to give (8.0 mg) Muricarpin (1): Syrup; IR (film) max cmÀ1: 3345, 1698, 1609, 1514, 1445, 1232; 1H NMR (CD3OD):  1.49 (4H, m, H2-5, H2-6), 2.37 (2H, t, J ¼ 6.8 Hz, H2-4), 2.39 (2H, t, J ¼ 6.8 Hz, H2-7), 2.67 (2H, m, H2-2), 2.73 (2H, m, H2-1), 6.45 (1H, dd, J ¼ 8.0 Hz, 2.0 Hz, H-600 ), 6.58 (1H, d, J ¼ 2.0 Hz, H-200 ), 6.64 (1H, d, J ¼ 8.0 Hz, H-500 ), 6.67 (2H, d, J ¼ 8.8 Hz, H-30 , H-50 ) and 6.97 (2H, d, J ¼ 8.8 Hz, H-20 , H-60 ); 13 C NMR (CD3OD):  24.3 (C-6), 30.2 (C-1), 32.2 (C-5), 35.9 (C-7), 43.7 (C-4), 45.4 (C-2), 116.2 (C-30 , C-50 ), 116.3 (C-500 ), 116.6 (C-200 ), 120.7 (C-600 ), 130.2 (C-20 , C-60 ), 133.3 (C-10 ), 135.3 (C-100 ), 144.2 (C-400 ), 146.1 (C-300 ), 156.6 (C-40 ) and 213.6 (C-3); Negative-ion HR-FABMS: m/z 313.1404 (Calcd for C19H21O4, [M–H]–, 313.1440) 1,7-Bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (2): Syrup; []25 D –10.2 (c ¼ 1.28, MeOH); IR (film) max cmÀ1 : 3367, 1730, 1606, 1522, 1445, 1375, 1281, 1113; 1H NMR (CD3OD):  1.28 (2H, m, H2-5), 1.52 (2H, m, H2-6), 1.56 (2H, m, H2-4), 1.75 (2H, m, H2-2), 1.97 (3H, s, 3-OAc), 2.42 (2H, m, H2-7), 2.44 (2H, m, H2-1), 4.83 (1H, quint., J ¼ 6.1 Hz, H-3), 6.45 (2H, dd, J ¼ 8.0 Hz, 1.6 Hz, H-60 , H-600 ), 6.58 (2H, d, J ¼ 1.6 Hz, H-20 , H-200 ), 6.64 (1H, d, J ¼ 8.0 Hz, H-500 ) and 6.65 (1H, d, J ¼ 8.0 Hz, H-50 ); 13C NMR (CD3OD):  25.6 (C-5), 32.1 (C-1), 32.4 (C-6), 34.9 (C-4), 35.9 (C-7), 37.1 (C-2), 75.3 (C-3), 116.2 (C-500 ), 116.4 (C-50 ), 116.5 (C-200 ), 116.6 (C-20 ), 120.6 (C-600 ), 120.7 (C-60 ), 134.6 (C-100 ), 135.4 (C-10 ), 144.1 (C-400 ), 144.3 (C-40 ), 146.0 (C-300 ), 146.1 (C-30 ) and 172.9/21.1 (3-OAc); Negative-ion HR-FABMS: m/z 373.1634 (Calcd for C21H25O6, [M–H]–, 373.1651) 1-(40 -Hydroxyphenyl)-7-(300 ,400 -dihydroxyphenyl)heptan-3-yl acetate (3): Syrup; []25 D – 4.4 (c ¼ 0.8, MeOH); IR (film) max cmÀ1: 3382, 1730, 1609, 1515, 1448, 1375, 1272, 1113; 1H NMR (CD3OD):  1.28 (2H, m, H2-5), 1.54 (2H, m, H2-6), 1.57 (2H, m, H2-4), 1.75 (2H, m, H2-2), 1.97 (3H, s, 3-OAc), 2.42 (2H, t, J ¼ 6.8 Hz, H2-7), 2.5 (2H, m, H2-1), 4.82 (1H, quint., J ¼ 6.4 Hz, H-3), 6.45 (1H, dd, J ¼ 8.0 Hz, 2.0 Hz, H-600 ), 6.58 (1H, d, J ¼ 2.0 Hz, H-200 ), 6.64 (1H, d, J ¼ 8.0 Hz, H-500 ), 6.67 (1H, d, J ¼ 8.6 Hz, H-30 , H-50 ) and 6.95 (1H, d, J ¼ 8.6 Hz, H-20 , H-60 ); 13C NMR (CD3OD):  25.6 (C-5), 31.9 (C-1), 32.4 (C-6), 34.9 (C-4), 35.9 (C-7), 37.2 (C-2), 75.3 (C-3), Natural Product Research 1199 Downloaded by [Memorial University of Newfoundland] at 01:11 01 August 2014 116.2 (C-30 , C-50 ), 116.3 (C-500 ), 116.6 (C-200 ), 120.7 (C-600 ), 130.2 (C-20 , C-60 ), 135.4 (C-100 ), 133.8 (C-10 ), 144.1 (C-400 ), 146.0 (C-300 ), 156.4 (C-40 ) and 173.0/21.1 (3-OAc); Negative-ion HR-FABMS: m/z 357.1710 (Calcd for C21H25O5, [M–H]–, 357.1702) 1-(30 ,40 -Hydroxyphenyl)-7-(400 -hydroxyphenyl)-heptan-3-one (4): Syrup; IR (film) max cmÀ1: 3278, 1698, 1609, 1514, 1446, 1234, 1111; 1H NMR (CD3OD):  1.49 (4H, m, H2-5, H2-6), 2.34 (4H, m, H2-4, H2-7), 2.69 (4H, m, H2-1, H2-2), 6.47 (1H, dd, J ¼ 8.8 Hz, 1.6 Hz, H-60 ), 6.59 (1H, br s, H-20 ), 6.64 (1H, d, J ¼ 8.8 Hz, H-50 ), 6.66 (2H, d, J ¼ 8.4 Hz, H-300 , H-500 ) and 6.94 (2H, d, J ¼ 8.4 Hz, H-200 , H-600 ); 13C NMR (CD3OD):  24.3 (C-6), 32.3 (C-5), 30.4 (C-1), 35.7 (C-7), 43.7 (C-4), 45.4 (C-2), 116.1 (C-300 , C-500 ), 116.4 (C-50 ), 116.5 (C-20 ), 120.5 (C-60 ), 130.2 (C-200 , C-600 ), 134.1 (C-10 ), 134.4 (C-100 ), 144.5 (C-40 ), 146.2 (C-30 ), 156.3 (C-400 ) and 213.6 (C-3); Negative-ion HR-FABMS: m/z 313.1443 (Calcd for C19H21O4, [M–H]–, 313.1440) (5R)-5-Hydroxy-1,7-bis(4-hydroxyphenyl)-3-heptanone (5): Syrup; []25 ỵ51.8 D (c ẳ 0.11, MeOH); IR (film) max cmÀ1: 3400, 1699, 1611, 1513, 1450, 1368, 1229; H NMR (CD3OD):  1.65 (2H, q br, J ¼ 6.4 Hz, H2-6), 2.47 (3H, m, H-4a, H2-7), 2.76 (5H, m, H2-1, H2-2, H-4b), 3.97 (1H, quint., J ¼ 6.4 Hz, H-5), 6.67 (2H, d, J ¼ 8.4 Hz, H-300 , H-500 ), 6.68 (2H, d, J ¼ 8.4 Hz, H-30 , H-50 ) and 6.98 (4H, d, J ¼ 8.4 Hz, H-20 , H-60 , H-200 , H-600 ) Acknowledgements The authors are grateful to the National Foundation for Science and Technology Development (NAFOSTED, Hanoi, Vietnam) and Vietnam National University, Hanoi (Hanoi, Vietnam) for the support in this work References Ali, M.S., Tezuka, Y., Awale, S., Banskota, A.H., & Kadota, S (2001) Six new diarylheptanoids from the seeds of Alpinia blepharocalyx Journal of Natural Products, 64, 289–293 Bratt, K., & Sunnerheim, K (1999) Synthesis and digestibility inhibition of diarylheptanoids: structure-activity relationship Journal of Chemical Ecology, 25, 2703–2713 Giang, P.M., Son, P.T., Matsunami, K., & Otsuka, H (2006) New diarylheptanoids from Amomum muricarpum Elmer Chemical and Pharmaceutical Bulletin, 54, 139–140 Itokawa, H., Morita, H., Midorikawa, I., Aiyama, R., & Morita, M (1985) Diarylheptanoids from the rhizomes of Alpinia officinarum Hance Chemical and Pharmaceutical Bulletin, 33, 4889–4893 Kikuzaki, H., Kawai, Y., & Nakatani, N (2001) 1,1-Diphenyl-2-picrylhydrazyl radical-scavenging active compounds from greater cardamom (Amomum subulatum Roxb.) 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