Next Article in Journal
3-Chlorokenpaullone
Previous Article in Journal
Methyl 2-[(2-{2-[(2-acetamidophenyl)ethynyl]benzamido} phenyl)ethynyl]benzoate
 
 
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Short Note

(S)-2-Methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one

1
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Padjadjaran University, Jalan Raya Bandung-Sumedang Km 21, Jatinangor 45363, Sumedang, Indonesia
2
Faculty of Pharmacy, Padjadjaran University, Jalan Raya Bandung-Sumedang Km 21, Jatinangor 45363, Sumedang, Indonesia
*
Author to whom correspondence should be addressed.
Molbank 2015, 2015(2), M855; https://doi.org/10.3390/M855
Submission received: 3 March 2015 / Revised: 16 April 2015 / Accepted: 17 April 2015 / Published: 21 April 2015

Abstract

:
A novel chromene, (S)-2-methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one (1), was isolated from the leaves of Peperomia pellucida (Piperaceae). The chemical structure of 1 was determined by spectroscopic methods and comparison with those related compounds previously reported.

Graphical Abstract

Introduction

The genus Peperomia is the second largest in the Piperaceae family and comprises more than 600 species widely distributed in Indonesia [1]. Previous phytochemical studies on the genus Peperomia have revealed the presence of a variety of compounds with interesting biological activities, including flavonoids [2,3,4], benzopyran derivatives [5,6,7], secolignans [8,9,10,11], terpenes, arylpropanoids, phenolic compounds [12,13,14,15] and essential oils [16]. Species of Peperomia have found application in folk medicine for the treatment of asthma and gastric ulcers, inflammation, and exhibit analgesic and antibaterial activities [17]. As part of our studies on the Indonesian Peperomia species, we have performed a phytochemical examination of leaves of P. pellucida. The plant, known as “sasaladaan” in Indonesia is a perennial herb that typically grows in wet rock crevices, and can be found from the northeast to the southeast of Indonesia [1]. The plant is used in Indonesian folk medicine for the treatment of fever, contused wound and skin diseases [18]. Although secondary metabolites of other Peperomia species have been investigated previously, the chemical composition of P. pellucida which grows in Indonesia is yet to be reported. The isolation and structure elucidation of the isolated compounds are described herein.

Results and Discussion

(S)-2-Methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one (1) (Figure 1), was obtained as an orange amorphous powder, [α]20D +25.1° (c, 0.2, MeOH), completely dissolved in acetone and showed green-light flourescence. Its molecular formula C22H28O3, was established from a combination analysis of the HR-ESI-TOFMS (m/z 341.2072 [M+H]+, calcd. for C22H28O3 340.2038) and NMR data (Table 1), thus requiring nine degrees of unsaturation. The IR spectrum showed the presence of ester lactone (1700 cm−1), gem-dimethyl 1385 and 1360 cm−1, aromatic (1590 and 1480 cm−1) and ether (1078 cm−1) moieties, while the UV spectrum showed three absorption maxima at 328, 280 and 256 nm (log ε 4.40, 3.76 and 3.20), indicating the aromatic character of 1. The 1H-NMR spectrum of 1 revealed two sets of singlet proton at δH 7.68 (1H, s) and 7.70 (1H, s), which implied the presence of a 2,3,5,6-tetrasubstituted benzene ring, a singlet at δH 2.08, corresponding to a methyl group attached to an oxygen bearing carbon. The 1H-NMR spectrum also showed signs of an olefinic proton at δH 4.10 (1H, m), of eight coupled aliphatic protons at δH 1.34 (2H, m) and 1.64 (2H, m), 1.26 (2H, m) and 1.27 (2H, m), of oxygenated methylene protons at δH 4.13 (2H, br.s), besides four methyl groups at δH 0.87 (6H, s), 1.26 (3H, s) and 1.27 (3H, s). The 13C-NMR spectrum showed 22 carbon resonances, which were classified by their chemical shifts and the HMQC spectrum as one carbonyl lactone, five methyls, five sp3 methylenes, three sp2 methines, seven sp2 quaternary carbons and one sp3 quaternary carbons. These functionalities accounted for six out of the total nine degrees of unsaturation. The remaining three degrees of unsaturation were consistent to chromene with one additional lactone ring. A comparison of the NMR data of 1 with those of lhotzchromene [19], revealed that the structures of the compounds are closely related, the main differences are the absence of cis-olefine, carboxyl group and one of the aromatic proton and the presence of a lactone ring in the side chain and two additional methyl groups. The gross structure of 1 was deduced from the 1H-1H COSY and HMBC spectra (Figure 2). The aromatic proton at δH 7.68 was correlated to C-4a (δC 127.1), C-6 (δC 129.2) and C-7 (δC 129.8), whereas another aromatic at δH 7.70 was correlated to C-8a (δC 152.1), C-7 (δC 129.8) and C-4a (δC 127.1) indicating a tetrasubstituted aromatic ring and the location of the aromatic protons in C-5 and C-8, respectively. The presence of a lactone ring is confirmed from correlation from oxygenated methylene protons at δH 4.13 to C-8 (δC 167.0), C-6 (δC 129.2) and C-1 (δC 131.7) and aromatic proton at C-8 (δH 7.70) to carbonyl lactone at C-9 (δC 167.0), demonstrating that the lactone ring should be attached at C-6 and C-7 formed by cyclization of carboxylic acid and hydroxyl from the side chain. The methyl proton at δH 0.87 and 1.26 were correlated to C-3" (δC 126.2) and C-1" (δC 131.7), suggesting that one of an isoprenyl moiety was attached at C-1" of the lactone ring. The methylene protons at δH 1.23 (H-3) and 1.34 (H-4) are mutually coupled and correlated to C-4a (δC 127.1), C-8a (δC 152.1) and C-2 (δC 56.5), suggested that pyran ring was located at C-2, C-3, C-4, C-4a, and C-8a. The correlations of methyl group at δH 2.08 with C-2 (δC 56.5), C-1' (δC 29.8) and C-3 (δC 29.8) observed for the one of the methyl group confirmed its position to an oxygenated carbon at C-2. The methylene protons at δH 1.27 (H-1') and 1.42 (H-2') are mutually coupled and correlated to C-2 (δC 56.5) and C-3' (δC 114.5), whereas olefinic proton at δH 4.10 (H-3') was correlated to C-2' (δC 22.4) and sp2 quartenary carbon at C-4' (δC 131.7), suggesting that the 4-methyl-3-pentenyl units were attached to C-2 of the of a pyrane ring. From the results of a NOESY experiment, it was evident that Me-5'-H-3' and Me-5"-H-2" had regiochemical relationship, therefore Me-5'-H-3' and Me-5"-H-2" has Z-configuration, respectively. The relative stereochemistry of C-2 was determined by NOESY experiments, pairs of NOESY correlations, H-1'/H-2' and Me-6'/H-3, suggested that the Me-6' was in β-oriented. The relative stereochemistry of C-2 is also confirmed according the structural similarity and optical rotation, [α]20D +25.1° to blandachromene I [19] and lhotzchromene [20], therefore the S-configuration at C-2 was suggested. Based on physicochemical properties and spectral data along with biogenetic point of view occurance of chromone constituents in Piperomia genus, consequently, the structure of the new chromene was determined to be (S)-2-methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one, and was named peperochromen A.

Experimental Section

General

Optical rotations were recorded on an ATAGO AP-300 automatic polarimeter. The UV-Visible spectra were obtained on Shimazu series 1800 spectrophotometer (Kyoto, Japan). The IR spectra were recorded on a Perkin-Elmer spectrum-100 FT-IR (Waltham, MA, USA) in KBr. Mass spectra were obtained with a Water, Qtof HR-MS XEVotm mass spectrometer. (Waters, Milford, MA, USA). 1H- and 13C-NMR spectra were obtained with a JEOL JNM A-500 spectrometer using TMS as internal standard (Tokyo, Japan). Chromatographic separations were carried out on silica gel 60 (Merck, Darmstadt, Germany). PTLC glass plates were precoated with silica gel GF254 (Merck, 0.25 mm). TLC plates were precoated with silica gel GF254 (Merck, 0.25 mm) and detection was achieved by spraying with 10% H2SO4 in ethanol, followed by heating.

Plant Material

The leaves of P. pellucida were collected in Sumedang, West Java Province, Indonesia in August 2012. The plant was identified by the staff of the Laboratory of Plant Taxonomy, Department of Biology, Padjadjaran University and a voucher specimen was deposited at the herbarium.

Extraction and Isolation

Dried ground leaves (4.5 kg) of P. pellucida were successively extracted in Soxhlet apparatus with n-hexane, EtOAc, n-BuOH and EtOH. Evaporation resulted in the crude extracts of n-hexane (117 g), EtOAc (125 g), n-BuOH (86 g), and MeOH (104 g), respectively. A portion of the EtOAc extract (120 g) was subjected to vacuum liquid chromatography using gradient elution of n-hexane/EtOAc/MeOH to afford 12 fractions (A01-A12). Fraction A01 (3.3 g) was subjected to silica gel column chromatography using mixtures of CH2Cl2/EtOAc (7:3) as eluting solvents to afford 10 fractions (B01-B10). Fraction B02 and B03 were combined (500 mg) and was subjected to silica gel column chromatography using mixtures of n-hexane/EtOAc (3:2) as eluting solvents to afford 10 fractions (D01-D10). Fraction D04 (300 mg) was preparative TLC on silica gel GF254, eluted with n-hexane/EtOAc (3:2) and CH2Cl2/EtOAc (9.5:0.5), to give 1 (11.5 mg).

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3Supplementary File 4

Acknowledgements

This research was supported by grants from Directorate General Higher Education, Ministry of Education and Culture, Indonesia (2012-2013 by YS).

Author Contributions

Unang Supratman designed the whole experiment and contributed to the manuscript. Yasmiwar Susilawati, Ricky Nugraha researched data and wrote the manuscript. Ahmad Muhtadi and Supriyatna Soetardjo analyzed the NMR and LCMS/MS spectra. All authors read and approved the final manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Heyne, K. The Useful Indonesian Plants; Research and Development Agency, Ministry of Forestry, Indonesia: Jakarta, Indonesia, 1982; pp. 1–462. [Google Scholar]
  2. Aqil, M.; Khan, I.Z.; Ahmad, M.B. Flavonoids from Peperomia pellucida. Sci. Phys. Sci. 1993, 5, 213–215. [Google Scholar]
  3. Mota, J.S.; Leite, A.C.; Kato, M.J.; Young, M.C.M.; Bolzani, V.S.; Furlan, M. Isoswertisin flavones and other constituents from Peperomia obtusifolia. Nat. Prod. Res. 2011, 20, 1–7. [Google Scholar] [CrossRef] [PubMed]
  4. Velozo, L.S.M.; Ferreira, M.J.P.; Santos, M.I.S.; Moreira, D.L.; Guimaraes, E.F.; Emerenciano, V.P.; Kaplan, M.A.C. C-glycosyl flavones from Peperomia blanda. Fitoterapia 2009, 80, 119–122. [Google Scholar] [CrossRef] [PubMed]
  5. Seeram, N.P.; Jacobs, H.; Mclean, S.; Reynolds, W.F. A prenylated benzopyran derivatives from Peperomia clusifolia. Phytochemistry 1998, 49, 1389–1391. [Google Scholar] [CrossRef]
  6. Mbah, J.A.; Tchuendem, M.H.K.; Tane, P.; Sterner, O. Two chromenes from Peperomia vulcanica. Phytochemistry 2002, 60, 799–801. [Google Scholar] [CrossRef]
  7. Salazar, K.J.; Paredes, G.E.D.; Lluncor, L.R.; Young, W.F. Chromenes of polyketide origin from Peperomia villipetiola. Phytochemistry 2005, 66, 573–579. [Google Scholar] [CrossRef] [PubMed]
  8. Chen, C.M.; Jan, F.Y.; Chen, M.T.; Lee, T.J. Peperomins A, B, and C, novel secolignans from Peperomia japonica. Heteocycles 1989, 29, 411–414. [Google Scholar] [CrossRef]
  9. Monache, F.D.; Compagnone, R.S. A secolignan from Peperomia flabella. Phytochemistry 1996, 43, 1097–1098. [Google Scholar] [CrossRef]
  10. Govindachari, T.R.; Kumari, K.G.N.; Partho, P.D. Two secolignans from Peperomia dindigulensis. Phytochemistry 1998, 49, 2129–2131. [Google Scholar] [CrossRef]
  11. Felippe, L.G.; Batista, J.M.; Baldoqui, D.C.; Nascimento, I.R.; Kato, M.J.; Bolzani, V.S.; Furlan, M. Structure and absolute configuration of a secolignan from Peperomia blanda. Phytochem. Lett. 2011, 4, 245–249. [Google Scholar] [CrossRef]
  12. Tanaka, T.; Asai, F.; Iinuma, M. Phenolic compounds from Peperomia obtusifolia. Phytochemistry 1998, 49, 229–232. [Google Scholar] [CrossRef]
  13. Moriera, D.L.; De Souza, P.O.; Kaplan, M.A.C.; Guimares, E.F. Essential oil analysis of four Peperomia species (Piperaceae). Acta Hortic. 1999, 500, 65–69. [Google Scholar] [CrossRef]
  14. Bayma, J.C.; Arruda, M.S.P.; Muller, A.H.; Arruda, A.C.; Canto, W.C.C. A dimeric ArC2 compound from Peperomia pellucida. Phytochemistry 2000, 55, 779–782. [Google Scholar] [CrossRef]
  15. Li, N.; Wu, J.L.; Sakai, J.; Ando, M. Dibenzylbutyrolactone and dibenzylbutanediol lignans from Piperomia duclouxii. J. Nat. Prod. 2003, 66, 1421–1426. [Google Scholar] [CrossRef] [PubMed]
  16. Zoghbi, M.G.B.; Andrade, A.H.A.; Lobato, R.C.L.; Tavares, A.C.C.; Souza, A.P.S.; Conceicao, C.C.C.; Guimares, E.F. Peperomia circinnata Link and Peperomia rotundifolia (L.) Kunth growing on different host-trees in Amazon: Volatiles and relationship with bryophytes. Biochem. Syst. Ecol. 2005, 33, 269–274. [Google Scholar] [CrossRef]
  17. Aziba, P.I.; Adedeji, A.; Ekor, M.; Adeyemi, O. Analgesic activity of Peperomia pellucida aerial parts in mice. Fitoterapia 2001, 72, 57–58. [Google Scholar] [CrossRef]
  18. Hutapea, J.R. Inventory of Indonesian Medicinal Plants; Research and Development Agency, Ministry of Health, Indonesia: Jakarta, Indonesia, 1994; pp. 1–156. [Google Scholar]
  19. Moreira, D.L.; Guimaraes, E.F.; Kaplan, M.A.C. Non-polar constituents from leaves of Piper lhotzkyanum. Phytochemistry 1998, 5, 1339–1342. [Google Scholar] [CrossRef]
  20. Velozo, L.S.M.; Ferreira, M.J.P.; Santos, M.I.S.; Moreira, D.L.; Emerenciano, V.P.; Kaplan, M.A.C. Unusual chromenes from Peperomia blanda. Phytochemistry 2006, 67, 492–496. [Google Scholar] [CrossRef] [PubMed]
Figure 1. (S)-2-Methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one (1).
Figure 1. (S)-2-Methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one (1).
Molbank 2015 m855 g001
Figure 2. Selected HMBC and COSY correlations for 1.
Figure 2. Selected HMBC and COSY correlations for 1.
Molbank 2015 m855 g002
Table 1. NMR data (500 MHz for 1H and 125 MHz for 13C, in CDCl3) for 1.
Table 1. NMR data (500 MHz for 1H and 125 MHz for 13C, in CDCl3) for 1.
Position13C-NMRδC (mult.)1H-NMRδH (integral, mult., J Hz)
256.5 (s) -
329.8 (t)1.23 (1H, m)
1.28 (1H, m)
422.4 (t)1.34 (1H, m)
1.64 (1H, m)
4a127.1 (s)-
5128.7 (d)7.68 (1H, s)
6129.2 (s)-
7129.8 (s)-
8131.6 (d)7.70 (1H, s)
8a152.1 (s)-
9167.0 (s)-
1'29.8 (t)1.26 (1H, m)
1.27 (1H, m)
2'31.0 (t)1.27 (1H, m)
1.42 (1H, m)
3'114.5 (d)4.10 (1H, m)
4'131.7 (s)
5'10.8 (q)0.87 (3H, s)
6'39.5 (q)2.08 (3H, s)
7'13.9 (q)1.27 (3H, s)
1"131.7 (s)-
2"67.4 (t)4.13 (2H, br.s)
3"126.2 (s)-
4"13.9 (q)1.26 (3H, s)
5"10.8 (q)0.87 (3H, s)

Share and Cite

MDPI and ACS Style

Susilawati, Y.; Nugraha, R.; Muhtadi, A.; Soetardjo, S.; Supratman, U. (S)-2-Methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one. Molbank 2015, 2015, M855. https://doi.org/10.3390/M855

AMA Style

Susilawati Y, Nugraha R, Muhtadi A, Soetardjo S, Supratman U. (S)-2-Methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one. Molbank. 2015; 2015(2):M855. https://doi.org/10.3390/M855

Chicago/Turabian Style

Susilawati, Yasmiwar, Ricky Nugraha, Ahmad Muhtadi, Supriyatna Soetardjo, and Unang Supratman. 2015. "(S)-2-Methyl-2-(4-methylpent-3-enyl)-6-(propan-2-ylidene)-3,4,6,7-tetrahydropyrano[4,3-g]chromen-9(2H)-one" Molbank 2015, no. 2: M855. https://doi.org/10.3390/M855

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop