Natural Product Communications 2013
Volume 8, Number 12 Contents
Original Paper Page
New Humulenes from Hyptis incana (Labiatae)
Mitsuru Satoh, Yoshio Satoh, Yasuhiro Anzai, Daisuke Ajisawa, Keiichi Matsuzaki, Mitsuko Makino and Yasuo Fujimoto 1665 Inhibitory Effects against Pasture Weeds in Brazilian Amazonia of Natural Products from the Marine Brown Alga
Dictyota menstrualis
Rainiomar Raimundo Fonseca, Antonio Pedro Silva Souza Filho, Roberto Campos Villaça and Valéria Laneuville Teixeira 1669 Isolation of the Plant Hormone (+)-Abscisic acid as an Antimycobacterial Constituent of the Medicinal Plant Endophyte
Nigrospora sp.
Trevor N. Clark, Katelyn Ellsworth, Haoxin Li, John A. Johnson and Christopher A. Gray 1673 New Cembranoid Diterpene from the South China Sea Soft Coral Sarcophyton sp.
Fei Cao, Jing Zhou, Kai-Xia Xu, Meng-Qi Zhang and Chang-Yun Wang 1675 Crotofolane Diterpenoids from Croton caracasanus
Katiuska Chávez, Reinaldo S. Compagnone, Ricarda Riina, Alexander Briceño, Teresa González, Emilio Squitieri,
Carlos Landaeta, Humberto Soscún and Alírica I. Suárez 1679 Development and Validation of a Modified Ultrasound-Assisted Extraction Method and a HPLC Method for the Quantitative
Determination of Two Triterpenic Acids in Hedyotis diffusa
Yu-Chiao Yang, Ming-Chi Wei, Hui-Fen Chiu and Ting-Chia Huang 1683
New Triterpenoid Saponins from the Roots of Saponaria officinalis
Barbara Moniuszko-Szajwaj, Łukasz Pecio, Mariusz Kowalczyk, Ana M. Simonet, Francisco A. Macias,
Małgorzata Szumacher-Strabel, Adam Cieślak, Wiesław Oleszek and Anna Stochmal 1687 Minor Triterpene Saponins from Underground Parts of Lysimachia thyrsiflora: Structure elucidation,
LC-ESI-MS/MS Quantification, and Biological Activity
Irma Podolak, Paweł Żmudzki, Paulina Koczurkiewicz, Marta Michalik, Paweł Zajdel and Agnieszka Galanty 1691 Variation of Saponin Contents and Physiological Status in Quillaja saponaria Under Different Environmental Conditions
Angélica Grandón S, Miguel Espinosa B, Darcy Ríos L, Manuel Sánchez O, Katia Sáez C, Víctor Hernández S. and José Becerra A 1697 New Access to 7,17-seco C19-Diterpenoid Alkaloids via Vacuum Pyrolysis of N-Deethyl-8-acetyl Derivatives
Ling Wang, Qi-Feng Chen and Feng-Peng Wang 1701
Alkaloids from Boophone haemanthoides (Amaryllidaceae)
Jerald J. Nair, Lucie Rárová, Miroslav Strnad, Jaume Bastida and Johannes van Staden 1705 Supinidine Viridiflorates from the Roots of Chromolaena pulchella
Mario A. Gómez-Hurtado, J. Martín Torres-Valencia, Rosa E. del Río, Gabriela Rodríguez-García, Virginia Motilva,
Sofía García-Mauriño, Carlos M. Cerda-García-Rojas and Pedro Joseph-Nathan 1711 N-Containing Metabolites from the Marine Sponge Agelas clathrodes
Fan Yang, Rui-Hua Ji, Jiang Li, Jian-Hong Gan and Hou-Wen Lin 1713 Two New Compounds and Anti-complementary Constituents from Amomum tsao-ko
Jiahong Jin, Zhihong Cheng and Daofeng Chen 1715
Antiangiogenic Activity of Flavonoids from Melia azedarach
Shigenori Kumazawa, Satomi Kubota, Haruna Yamamoto, Naoki Okamura, Yasumasa Sugiyama, Hirokazu Kobayashi,
Motoyasu Nakanishi and Toshiro Ohta 1719
Application of Mixture Analysis to Crude Materials from Natural Resources (IV)[1(a-c)]: Identification of Glycyrrhiza Species by Direct Analysis in Real Time Mass Spectrometry (II)
Eriko Fukuda, Yoshihiro Uesawa, Masaki Baba and Yoshihito Okada 1721 Comparison of Total Phenolic Content, Scavenging Activity and HPLC-ESI-MS/MS Profiles of Both Young and Mature
Leaves and Stems of Andrographis paniculata
Lee Suan Chua, Ken Choy Yap and Indu Bala Jaganath 1725
Xanthones from aerial parts of Hypericum laricifolium Juss.
Irama Ramírez-González, Juan Manuel Amaro-Luis and Alí Bahsas 1731
A New Xanthone from the Pericarp of Garcinia mangostana
Manqin Fu, Samuel X. Qiu, Yujuan Xu, Jijun Wu, Yulong Chen, Yuanshan Yu and Gengsheng Xiao 1733 Isolation of a Phomoxanthone A Derivative, a New Metabolite of Tetrahydroxanthone, from a Phomopsis sp. Isolated
from the Mangrove, Rhizhopora mucronata
Yoshihito Shiono, Takehiro Sasaki, Fumiaki Shibuya, Yukito Yasuda, Takuya Koseki and Unang Supratman 1735 Anti-allergic Inflammatory Effects of Cyanogenic and Phenolic Glycosides from the Seed of Prunus persica
Geum Jin Kim, Hyun Gyu Choi, Ji Hyang Kim, Sang Hyun Kim, Jeong Ah Kim and Seung Ho Lee 1739 Isolation, Synthesis and Biological Evaluation of Phenylpropanoids from the Rhizomes of Alpania galanga
Sumit S Chourasiya, Eppakayala Sreedhar, K. Suresh Babu, Nagula Shankaraiah, V. Lakshma Nayak, S. Ramakrishna,S. Sravani and
M.V. Basaveswara Rao 1741
Continued inside backcover
New Butenolide and Pentenolide from Dysidea cinerea
Phan Van Kiema,*, Nguyen Xuan Nhiema, Ngo Van Quangc, Chau Van Minha, Nguyen Hoai Nama, Nguyen Thi Cuca, Hoang Le Tuan Anha, Bui Huu Taia, Pham Hai Yena, Nguyen Xuan Cuonga, Nguyen Phuong Thaoa, Nguyen Thi Hoaid, Nan Young Kimb, Seon Ju Parkb and Kim Seung Hyunb,*
aInstitute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi, Vietnam
bCollege of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon 406-840, Korea
cInstitute of Chemistry, VAST, 18 Hoang Quoc Viet, Caugiay, Hanoi, Vietnam
dFaculty of Pharmacy, Hue University of Pharmacy and Medicine, Hue, Vietnam
[email protected]; [email protected]
Received: September 26th, 2013; Accepted: October 10th, 2013
Two new butenolide and pentenolide derivatives, dysideolides A-B, were isolated from the marine sponge Dysidea cinerea. Their structures were determined by the combination of spectroscopic and chemical methods, including 1D- and 2D-NMR spectroscopy, and CD spectra, as well as by comparing with the NMR data reported in the literature.
Keywords: Dysidea cinerea, Dysideidae, Dysideolide A, Dysideolide B, Marine sponge, Circular dichroism.
The marine sponge Dysidea cinerea Keller (Dysideidae) is distributed in the Red Sea, Western India, and Zanzibar. Marine sponges are a prolific source of anti-HIV proteins and study on chemical components of D. cinerea has led to the isolation of avarol and avarone derivatives [1a]. Several biological activities, such as anti-cytotoxic activity and inhibition of human immunodeficiency virus type 1 reverse transcriptase [1b,c], have also been reported. In the course of study of the chemical constituents of D. cinerea, butenolide and pentenolide derivatives were isolated (Figure 1).
Compound 1 was isolated as colorless oil and its molecular formula was determined as C13H22O3 from the ion at m/z 225.1490 [M–H]– in the HR ESI MS (Calcd. for C13H21O3: 225.1496). The 1H NMR spectrum of 1 showed: one olefinic proton at δH 5.84, two oxymethine protons at δH 3.86 and 4.91, and one tertiary methyl group at δH 2.10. The 13C NMR and DEPT spectra of 1 revealed 13 carbon signals, including one carbonyl (δC 176.3), one quaternary (δC 170.6), three methine (δC70.0, 88.9, and 118.0), six methylene (δC 23.7, 27.2, 30.4, 30.6, 33.0, and 34.9), and two methyl carbons (δC 14.0 and 14.4) (Table 1). The 1H and 13C NMR data of 1 were very similar to those of 4,10-dihydroxy-10-methyl-dodec-2-en-1,4- olide, except for the position of the hydroxyl group at C-5 [2]. The long range correlations between H-4 (δH 4.91) and C-1 (δC 176.3), C-2 (δC 118.0), C-3 (δC 170.60, and 3-Me (δC 14.0); between 3-Me (δH 2.10) and C-2 (δC 118.0), C-3 (δC 170.6), and C-4 (δC 88.9) in the HMBC spectrum (Figure 2) suggested that compound 1 had an α,β-unsaturated lactone and the methyl group was located at C-3.
Furthermore, the hydroxyl group at C-5 was confirmed by the HMBC correlation between H-5 (δH 3.86) and C-3 (δC 170.6), C-4 (δC 88.9), and C-6 (δC 34.9), and by COSY correlations between H-4 (δH 4.91) and H-5 (δH 3.86); and between H-5 (δH 3.86) and H-6 (δH 1.62). The absolute configuration of 1 was determined by circular dichroism. The CD spectrum of 1 showed a positive peak at 207 nm, consistent with those of compound 1a (a positive peak at 203 nm) [3a]. Therefore, the stereochemistry at C-4 of 1 was proved to be R. The remaining configuration at C-5 was determined by the advanced Mosher’s method [3b]. Treatment of 1 with (S)- and
Figure 1: Structures of compounds 1 – 2 and reference compounds.
(R)-R-methoxy-R-(trifluoromethyl)phenylacetyl (MTPA) chlorides using catalytic DMAPafforded (S)- and (R)-MTPA esters (1s and 1r), respectively. Analysis of the proton chemical shift differences between its (S)- and (R)-MTPA esters showed negative ΔδH signs for H-2(-0.03), H-4 (-0.06), and 3-Me (-0.03),and positive signs for H-5(+0.03), and H-12 (+0.02). This distribution of Δδ signs enabled assignment of the R configuration to C-5. Consequently, compound 1 was elucidated to be (4R,5R)-4,5-dihydroxy-3-methyldodec-2-en- 1,4-olide, and named dysedeolide A.
Compound 2 was isolated as colorless oil and its molecular formula was determined to be C13H22O3 by the HRESIMS ion at m/z 225.1491 [M–H]– (Calcd. for C13H21O3: 225.1496). The 1H NMR spectrum of 2 showed: one olefinic proton at δH 5.78, two oxymethine protons at δH 4.07 and 4.22, and one tertiary methyl group at δH 2.03. The 13C NMR and DEPT spectra of 2 revealed 13 carbon signals, including one carbonyl (δC 163.5), one quaternary (δC 158.9), three methine (δC 69.4, 81.8, and116.7), six methylene (δC22.6, 24.9, 29.1, 29.3, 31.7, and 32.7), and two methyl carbons (δC14.1 and 19.1). The 1H- and 13C NMR data of 2 were very similar to those of dysideolide A, except for the butenolide group replaced by a penteolide group. The HMBC correlations between H-5 (δH 4.22) and C-3 (δC 158.9), C-4 (δC 69.4), and C-7 (δC 24.9);
between 3-Me (δH 2.03) and C-2 (δC 116.7), C-3 (δC158.9), and C-4 (δC 69.4) suggested that compound 2 had an α,β-unsaturated-δ- lactone and the methyl group was at C-3. In addition, the hydroxyl
NPC Natural Product Communications Vol. 8 2013
No. 12
1751 - 1752
1752 Natural Product Communications Vol. 8 (12) 2013 Kiem et al.
Table 1: NMR spectral data for compounds 1– 2.
Pos. 1 2
δCa,c) δHa,d) (mult., J in Hz) δCb,c) δHb,d) (mult., J in Hz)
1 176.3 - 163.5 -
2 118.0 5.84 (s) 116.7 5.78 (s)
3 170.6 - 158.9 -
4 88.9 4.91 (s) 69.4 4.07 (d, 7.6) 5 70.0 3.86 (t, 6.4) 81.8 4.22 (dt, 3.6, 7.6) 6 34.9 1.62 (m) 32.7 1.67 (m), 1.75 (m) 7 27.2 1.37, 1.51 24.9 1.41, 1.55
8 30.6 1.31 29.3 1.27
9 30.4 1.31 29.1 1.27
10 33.0 1.29 31.7 1.23
11 23.7 1.30 22.6 1.25
12 14.4 0.88 (t, 6.5) 14.1 0.86 (t, 6.5) 3-Me 14.0 2.10 (s) 19.1 2.03 (s)
a)CD3OD, b)CDCl3, c)100 MHz, d)400 MHz, Assignments were made by HMQC, HMBC, and COSY experiments.
Figure 2: Key HMBC and COSY correlations of 1 – 2.
group at C-4 was confirmed by the HMBC correlations between H-4 (δH 4.07) and C-2 (δC 116.7), C-5 (δC 81.8), and C-6 (δC 32.7), and COSY correlations between H-4 (δH 4.07) and H-5 (δH 4.22) and H-6 (δH 1.67 and 1.75). The absolute configuration at C-5 of 2 was fixed by CD measurements and comparison with 2a [3c]. The CD spectrum of 2 showed a positive peak at 219 nm, while compound 2a showed a negative peak at 221 nm (5S configuration) [3c]. Based on this evidence, the stereochemistry at C-5 was proved to be R. Moreover, the coupling constant between H-4 and H-5 in the hexacyclic ester of 2, J4-5 = 7.6 Hz, confirmed the threo of the both protons H-4 and H-5 by comparing coupling constant of two erythro protons of 2a, J4-5 = 3.0 Hz [3c] and threo protons of 2b, J4-5 = 8.8 Hz [3d]. Based on the above evidence, compound 2 was elucidated as (4S,5R)-4,5-dihydroxy-3-methyldodec-2-en-1,5-olide, and named dysideolide B.
Experimental
General: The NMR spectra were recorded on an Agilent 400-MR spectrometer using TMS as internal standard. The HRESIMS were obtained using an AGILENT 6550 iFunnel Q-TOF LC/MS system.
Optical rotations were determined on a Jasco DIP-370 automatic polarimeter. Circular dichroism spectra were determined on a ChirascanTM CD spectrometer. Preparative HPLC was carried out using an AGILENT 1200 HPLC system. CC was performed using either silica-gel (Kiesel gel 60, 70-230 mesh and 230-400 mesh, Merck) or YMC RP-18 resin (30 - 50 µm, Fuji silisa Chemical Ltd.), and TLC by using pre-coated silica-gel 60 F254 (0.25 mm, Merck) and RP-18 F254S plates (0.25 mm, Merck).
Sponge material: D. cinerea was collected in Lang Co beach, Vietnam during August 2011, and identified by Dr Do Cong Thung, Institute of Marine Resources and Environment. A voucher specimen (DC1108) was deposited at the Herbarium of the Institute of Marine Biochemistry, VAST.
Extraction and isolation: Freeze dried tissue of D. cinerea (1.0 kg) was cleaned to remove sodium chloride and then extracted 3 times with MeOH under reflux for 15 h to yield 60 g of a dark solid extract. This was suspended in water and partitioned with CHCl3 to obtain CHCl3 (DC1, 20.0 g) and water extracts (DC2, 40 g) after removal of the solvents in vacuo. The DC1 extract (20.0 g) was chromatographed on a silica gel column eluting with a gradient of n-hexane – acetone (40 : 1 → 0 : 1, v/v) to obtain 5 sub-fractions, DC1A (3.2 g), DC1B (4.5 g), DC1C (3.3g), DC1D (3.1 g), and DC1E (5.0 g). The sub-fraction DC1B (4.5 g) was chromatographed on a silica gel column eluting with n-hexane – EtOAc (10 : 1, v/v) to give 3 smaller fractions, DC1B1 (1.0 g), DC1B2 (1.5 g), and DC1B3 (1.7 g). Fraction DC1B2 was chromatographed on an YMC RP-18 column eluting with MeOH – water (5 : 1, v/v) to give 3 fractions, DC1B2A (450 mg), DC1B2B (200 mg), and DC1B2C (400 mg). Fraction DC1B2B was chromatographed by HPLC using J’sphere ODS H-80, 250 mm × 20 mm, and 35% acetonitrile in water at a flow rate of 3 mL/min to yield 1 (7.0 mg) and 2 (6.0 mg).
Dysideolide A (1) Colorless oil.
25D: +45 (c 0.1, MeOH);CD [θ]207: + 2.2 × 104 (c 5.0 ×10-4, MeOH).
1H and 13C NMR (CD3OD): Table 1.
HRESIMS found m/z: 225.1490 [M – H]– (Calcd. for C13H21O3: 225.1496).
(S)-MTPA ester of 1 (1s)
1H NMR (500 MHz,CDCl3):δH 5.86 (H-2), 4.79 (H-4), 4.61 (H-5), 0.89 (H-12), and 2.13 (3-Me).
(R)-MTPA ester of 1 (1r)
1H NMR (500 MHz, CDCl3):δH 5.89 (H-2), 4.85 (H-4), 4.58 (H-5), 0.87 (H-12), and 2.16 (3-Me).
Dysideolide B (2) Colorless oil.
25D: +35 (c 0.1, MeOH).CD [θ]219 + 2.2 × 104 (c 5.0 ×10-4, MeOH).
1H and 13C NMR (CDCl3, 400 MHz): Table 1.
HRESIMS found m/z: 225.1491 [M – H]– (Calcd. for C13H21O3: 225.1496).
Acknowledgments - This study was financially supported by Vietnam 02/2011/HD-NCCBUD Project and partiallysupported by the National Research Foundation of Korea(NRF).
References
[1] (a) Hirsch S, Rudi A, Kashman Y, Loya Y. (1991) Newavarone and avarol derivatives from the marine sponge Dysidea cinerea. Journal of Natural Products, 54, 92-97; (b) Rudi A, Yosief T, Schleyer M, Kashman Y. (1999) Bilosespens A and B: Two novel cytotoxic sesterpenes from the marine sponge Dysidea cinerea. Organic Letters, 1, 471-472; (c) Loya S, Hizi A. (1990) The inhibition of human immunodeficiency virus type 1 reverse transcriptase by avarol and avarone derivatives. FEBS Letters, 269, 131-134.
[2] Mukku VJRV, Speitling M, Laatsch H, Helmke E. (2000) New butenolides from two marine Streptomycetes. Journal of Natural Products, 63, 1570-1572.
[3] (a) Gawronski JK, van Oeveren A, van der Deen H, Leung CW, Feringa BL. (1996) Simple circular dichroism method for the determination of absolute configuration of 5-substituted 2(5H)-furanones. The Journal of Organic Chemistry, 61, 1513-1515; (b) Nhiem NX, Kiem PV, Minh CV, Kim N, Park S, Lee HY, Kim ES, Kim YH, Kim S, Koh Y-S, Kim SH. (2013) Diarylheptanoids and flavonoids from Viscum album inhibit LPS- stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells. Journal of Natural Products, 76, 495-502; (c) Yu YM, Yang JS, Peng CZ, Caer V, Cong PZ, Zou ZM, Lu Y, Yang SY, Gu YC. (2009) Lactones from Angiopteriscaudatiformis.Journal of Natural Products, 72, 921-924. (d) Buchanan MS, Hashimoto T, Takaoka S, Asakawa Y. (1995) (+)-Osmundalactone, γ-lactones and spiromentins from the fungus Paxillus atrotomentosus. Phytochemistry, 40, 1251-1257.
