Sessiline, A New Nitrogenous Compound from the Fruits of Acanthopanax sessiliflorus

• Abstract
• Materials and Methods
• Acknowledgements
• References

Abstract

A new nitrogenous compound, named sessiline [5-(5-oxo-pyrrolidin-2-yloxymethyl)-furan-2-carbaldehyde (1)], was isolated from the fruits of Acanthopanax sessiliflorus, together with (-)-sesamin, scoparone, protocatechuic acid, ursolic acid, hyperin and 5-hydroxymethylfurfural by CC. The structures of these compounds were elucidated by physico-chemical and spectral analysis.

Acanthopanax species are herbaceous genus of the family Araliaceae that are distributed in Korea, Japan and China, and have traditionally been used as a tonic and a sedative, as well as in the treatment of rheumatism and diabetes [1]. Among fifteen species of Acanthopanax growing in the Korean peninsula, A. sessiliflorus and A. chiisanensis are the most abundant. Investigations on the compounds of A. sessiliflorus have revealed the presence of liriodendrin in the cortex [2] and stigmasterol, β-sitosterol, campesterol and (+)-sesamin in the root bark [3]. Only a few compounds, including saturated and unsaturated fatty acids have been isolated from the seeds of A. sessiliflorus [4]. 6-Hydroxyhexadeca-12Z-enoic, 6-hydroxyhexadeca-9Z,12Z-dienoic, and the isomeric 6- and 7-hydroxyoctadeca-12Z-enoic, and 6- and 7-hydroxyoctadeca-9Z,12Z-dienoic acids were isolated from the fruits of A. sessiliflorus [5]. During the course of our continued studies on the compounds from the fruits of A. sessiliflorus, a new nitrogenous compound, sessiline (1), was isolated and identified, together with (-)-sesamin, scoparone, protocatechuic acid, ursolic acid, hyperin and 5-hydroxymethylfurfural. Compound 1 is described here for the first time as a naturally occurring compound.

Compound 1 was obtained as yellow crystals from MeOH. The UV spectrum of 1 showed absorption bands at λ_max 223 and 278 nm. The EIMS of 1 showed an [M]⁺ ion at m/z 209. In the EIMS, the 5-hydroxymethylfurfural moiety showed an ion at m/z 126, together with the 5′-hydroxy-α-pyrrolidone moiety at m/z 83 and 84 [6]. The HRCIMS of 1 showed a quasi-molecular ion [M + H]⁺ at m/z 210.0776 for the molecular formula C₁₀H₁₁O₄N. The IR spectrum of 1 showed absorption bands for an amide at 3184 and 3116 cm^-1, an aldehyde at 1698 cm^-1, a lactam C = O at 1669 cm^-1, and C-O stretching at 1060 and 1033 cm^-1. The ¹H- and ¹³C-NMR spectra were very similar to those of α-pyrrolidone [7] and 5-hydroxymethylfurfural [8]. The typical furan ring protons were observed at δ 6.73 (d, J = 3.4 Hz) and 7.51 (d, J = 3.4 Hz), together with an aldehyde at δ 9.58 and oxymethylene protons at δ 4.59 and 4.49 indicating the 5-hydroxymethylfurfural moiety. Two pairs of methylene protons at δ 2.21, 1.89, 2.29 and 2.05, and an oxymethine proton at δ 5.01 were observed for the 5′-hydroxy-α-pyrrolidone moiety. Its ¹³C-NMR spectrum showed signals for the carbons of an aldehyde at δ 178.7, the carbonyl of lactam at δ 178.0 and an oxymethylene at δ 60.7. The assignments of the ¹H- and ¹³C-NMR signals derived hetero nuclear direct and long-range correlations on 1 are listed in Table [1]. In the homo COSY spectrum, the correlation of proton signals is indicated: H-3 correlates with H-4; H-3′ with H-4′. Accordingly, compound 1 was assigned as a new nitrogenous compound with an unusual structural skeleton and named sessiline [5-(5-oxo-pyrrolidin-2-yloxymethyl)-furan-2-carbaldehyde]. Compound 1 was found to be racemic. α-Pyrrolidone was previously isolated from red ginseng [9] and 5-hydroxymethylfurfural from Prunus mume [10]. Sessiline is the first example of a nitrogenous compound in which a 5′-hydroxy-α-pyrrolidone moiety is coupled with a 5-hydroxymethylfurfural moiety.

The structures of known compounds were elucidated as (-)-sesamin {[α]_D ²⁵: -87.5 (c 1.08, CHCl₃)} [11], scoparone [12], protocatechuic acid [13], ursolic acid {[α]_D ²⁵: + 65.5 (c 0.20, EtOH)} [14], hyperin [15] and 5-hydroxymethylfurfural [8] on the basis of the comparison of physico-chemical and spectral analysis with those of the authentic samples. Among them, scoparone, protocatechuic acid, ursolic acid, hyperin and 5-hydroxymethylfurfural are first isolated from this plant parts.

Materials and Methods

The fruits of Acanthopanax sessiliflorus were collected at Kong Ju, Korea, in Oct. 1999, and authenticated by Prof. Seon Haeng Cho, Kong Ju University of Education, Korea. A voucher specimen (No. Shin 9910-1) has been deposited at the Herbarium of Natural Products Research Institute (NPRI), Seoul National University, Korea. The air-dried powdered fruits (2 kg) were extracted with MeOH (10 liters × 3) under reflux. The MeOH extract (672 g) was evaporated in vacuo, suspended in water and fractionated successively with n-hexane (52 g), CHCl₃ (49 g), EtOAc (31 g) and n-BuOH (75 g). The n-hexane and CHCl₃ fraction (20 g) was chromatographed on silica gel (600 g) eluting with a gradient of n-hexane-EtOAc to afford (-)-sesamin (90 : 10, 5 mg) and scoparone (80 : 20, 11 mg). The EtOAc fraction (20 g) was chromatographed on silica gel (600 g) eluting with a gradient of n-hexane-EtOAc to afford protocatechuic acid (70 : 30, 12 mg) and ursolic acid (20 : 80, 21 mg), and eluting with a gradient of EtOAc-MeOH to afford hyperin (90 : 10, 153 mg). The n-BuOH fraction (20 g) was chromatographed on silica gel (600 g) eluting with a gradient of CHCl₃-MeOH to afford 5-hydroxymethylfurfural (97 : 3, 15 mg) and sessiline (1) (90 : 10, 23 mg).

Sessiline (1): [α]_D ²⁵: 0° (c 0.08, MeOH); UV (MeOH): λ_max log = 223 (3.58), 278 (4.17) nm; m.p.: 171 - 172 °C; TLC: R_f 0.5 (CHCl₃ : MeOH = 4 : 1, Kieselgel 60 F₂₅₄); IR ν_max (KBr): see text; ¹H-NMR (400 MHz, DMSO-d ₆) and ¹³C-NMR (100 MHz, DMSO-d ₆): see Table [1]; EIMS (70 eV, rel. int.): m/z = 209 [M]⁺ (4), 126 (100), 125 (13), 109 (19), 97 (84), 84 (66), 83 (49), 69 (21), 55 (21); FABMS: m/z = 210 [M + H]⁺; CIMS (Methane, rel. int.): m/z = 238 [M + C₂H₅]⁺ (4), 210 [M + H]⁺ (49), 127 (89), 109 (63), 97 (6), 84 (100), 83 (6), 56 (2); HRCIMS: m/z = 210.0776 ([M + H]⁺, 210.0766 of calcd).

Acknowledgements

This work was partly supported by the Brain Korea 21 Project, the Joint Research Program under the Japan-Korea Basic Scientific Cooperation Program (JSPS 147, KOSEF 996-0700-003-2) and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University.

References

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Prof. Dr. Bak-Kwang Kim

College of Pharmacy

Seoul National University

Seoul 151-742

Korea

Email: kimbk2@plaza.snu.ac.kr

Phone: +82-2-880-7841

Fax: +82-2-878-1652

References

• 1 Perry L M. Medicinal Plants of East and Southeast Asia. MIT press Cambridge, Massachusetts and London; 1980: p. 41
  Search in Google Scholar
• 2 Ro H S, Lee S Y, Han B H. Studies on the lignan glycoside of Acanthopanax cortex.  J Pharm Soc Kor. 1977;  21 81-6
  PubMedSearch in Google Scholar
• 3 Yook C S, Lee D H, Seo Y K, Ryu K S. Studies on the constituents in the root bark of Acanthopanax sessiliflorus Seemann.  Kor J Pharmacogn. 1977;  8 31-4
  PubMedSearch in Google Scholar
• 4 Kim C W, Kim S K. Studies on the constituents of seeds of Acanthopanax sessiliflorus Seemann.  Kor J Pharmacogn. 1987;  18 184-7
  PubMedSearch in Google Scholar
• 5 Asilbekova D T, Gusakova S D, Glushenkova A I. New hydroxy fatty acids of Acanthopanax sessiliflorus .  Khim Prir Soed. 1991;  5 616-9
  PubMedSearch in Google Scholar
• 6 Heyns K, Stute R, Scharmann H. Massenspektrometrische Untersuchungen-X II. Die Massenspektren von Furanen.  Tetrahedron. 1966;  22 2223-35
  CrossrefPubMedSearch in Google Scholar
• 7 Fronza G, Mondelli R, Randall E W, Gardini G -P. 13C nuclear magnetic resonance of N-heterocycles. J Chem Soc Perkin Trans 2 1977: 1746-9
  Search in Google Scholar
• 8 Shimizu M, Zenko Y, Tanaka R, Matsuzawa T, Morita N. Studies on aldose reductase inhibitors from natural products. V. Active components of Hachimi-jio-gan (Kampo medicine).  Chem Pharm Bull. 1993;  41 1469-71
  PubMedSearch in Google Scholar
• 9 Woo L K, Suh C S, Jhang J J, Shin K H. Presence of α-pyrrolidone in ginseng extracts.  Yakhak Hoeji. 1969;  13 121-4
  PubMedSearch in Google Scholar
• 10 Kwack Y S, Ryu S H, Baek B K, Lee J K, Ahn B Z. The anthelmintic principle of ”O-Mae”, the roasted fruits of Prunus mume, against Clonorchis sinensis .  Yakhak Hoeji. 1985;  29 32-8
  PubMedSearch in Google Scholar
• 11 Ina H, Asai A, Iida H, Ushida T. Chemical investigation of Hydrocotyle sibthorpioides .  Planta Med. 1987;  53 228
  PubMedSearch in Google Scholar
• 12 Joseph-Nathan P, Dominguez M, Ortega D A. Shift reagent ¹H-NMR study of methoxycoumarins.  J Heterocyclic Chem. 1984;  21 1141-4
  PubMedSearch in Google Scholar
• 13 Scott K N. Carbon-13 nuclear magnetic resonance of biologically important aromatic acid. I. Chemical shifts of benzoic acid and derivatives.  J Am Chem Soc. 1972;  94 8564-8
  CrossrefPubMedSearch in Google Scholar
• 14 Numata A, Yang P, Takahashi C, Fujiki R, Nabae M, Fujita E. Cytotoxic triterpenes from a Chinese medicine, Goreishi.  Chem Pharm Bull. 1989;  37 648-51
  CrossrefPubMedSearch in Google Scholar
• 15 Yasukawa K, Takido M. A flavonol glycoside from Lysimachia mauritiana .  Phytochemistry. 1987;  26 1224-6
  CrossrefPubMedSearch in Google Scholar

Prof. Dr. Bak-Kwang Kim

College of Pharmacy

Seoul National University

Seoul 151-742

Korea

Email: kimbk2@plaza.snu.ac.kr

Phone: +82-2-880-7841

Fax: +82-2-878-1652