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Fusiformines A and B: new indole alkaloids from Melodinus fusiformis

  • Yong-chao Li EMAIL logo , Jing Yang , Xiu-ren Zhou , Xin-hong Liang and Qing-yun Fu
Published/Copyright: January 30, 2016
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Zeitschrift für Naturforschung B
From the journal Zeitschrift für Naturforschung B Volume 71 Issue 3

Abstract

Fusiformines A (1) and B (2), two new monoterpenoid indole alkaloids, were isolated from the twigs and leaves of Melodinus fusiformis. Their structures were established by extensive spectroscopic techniques, including 2D NMR spectroscopy and mass spectrometry.

Keywords: fusiformine A; fusiformine B; Melodinus fusiformis; monoterpenoid indole alkaloids

1 Introduction

Monoterpenoid indole alkaloids elaborated mainly by plants of Apocynaceae family have been attractive targets for chemists for several decades [1–3]. The genus Melodinus (Apocynaceae family) comprises about 50 species and were distributed mainly in tropical or subtropical Asia and Australia [4]. In recent years, a series of novel alkaloids with highly complex polycyclic skeletons and interesting biological activities have been isolated and identified from the genus Melodinus, such as melohenines A and B [5], melotenine A [6], and melodinines H–K [7]. In the current study, two new monoterpenoid indole alkaloids, fusiformines A and B (1 and 2), were isolated from the twigs and leaves of Melodinus fusiformis. Herein, we describe the isolation and structure elucidation of the new alkaloids 1 and 2.

2 Results and discussion

Fusiformine A (1) had the molecular formula of C22H26N2O4, as established by HR-ESI-MS (m/z = 383.1893, [M+H]+; calcd. 383.1893), with 11 degrees of unsaturation. IR absorptions at 3384, 1675, and 1615 cm−1 as well as UV absorptions at 327 and 246 nm indicated the presence of hydroxyl and β-anilinoacrylate functionalities, respectively [8]. The distortionless enhancement by polarization transfer (DEPT) and 13C NMR spectra (Table 1) revealed 22 carbon signals, including 1 methyl and 1 methoxy groups, 6 methylenes (one oxygenated carbon atom), 6 methines (five olefinic carbon atoms), and 8 quaternary carbon atoms (five olefinic carbon atoms and one ester carbonyl group). Detailed analysis of the NMR data of 1 (Table 1) indicated that 1 was an aspidosperma-type monoterpenoid indole alkaloid and has a great similarity with the known compound 11-methoxytabersonine [9]. The striking difference was the presence of an oxygenated methylene group (δH = 3.51, m, 2H; δC = 58.8 ppm) in 1 instead of a methyl group in 11-methoxytabersonine. 1H–1H correlation spectroscopy (COSY) correlations of H2-18 (δH = 3.51 ppm, m, 2H) and H2-19 (δH = 1.30 ppm, ddd, J = 14.0, 8.0, 4.0 Hz; 1.21, ddd, J = 14.0, 8.0, 6.8 Hz), and the key heteronuclear multiple-bond correlations (HMBC) of H2-18 with C-20 (δC = 40.4 ppm) and H-19 with C-15 (δC = 133.3 ppm) and C-17 (δC = 29.5 ppm) confirmed the oxygenated methylene group (δC = 58.8 ppm), which was assigned as C-18. Thus, the gross structure of fusiformine A was established as 1, as shown in Fig. 1a. The relative stereochemistry of 1 elucidated by a rotating frame Overhauser effect spectroscopy (ROESY) spectrum was identical with that of 11-methoxytabersonine (Fig. 1b).

Table 1

1H and 13C data of fusiformines A (1) and B (2).

No.1 (CDCl3)a2 (CD3OD)b
δH (mult., J in Hz)δCδH (mult., J in Hz)δC
2–167.1–67.3
3a3.46 (dd, 15.6, 5.2)50.54.55 (dt, 17.4, 3.0)66.8
3b3.18 (d, 15.6)4.23 (dt, 17.4, 3.0)
5a3.02 (t, 7.2)50.84.06 (ddd, 12.0, 10.2, 8.4)70.9
5b2.68 (td, 7.2, 3.6)3.72 (ddd, 12.0, 9.0, 3.0)
6a2.04 (td, 15.6, 6.8)44.63.11 (ddd, 14.4, 8.4, 3.0)33.2
6b1.77 (dd, 11.6, 4.4)1.98 (ddd, 14.4, 10.2, 6.0)
7–54.5–59.0
8–130.1–138.2
97.10 (d, 8.4)121.87.94 (dd, 7.8, 1.2)126.6
106.39 (d, 8.4)105.16.71 (td, 7.8, 1.2)120.7
11–160.17.02 (td, 7.8, 1.2)129.2
126.42 (d, 2.0)96.86.66 (d, 7.8)111.8
13–144.3–151.2
145.77 (dd, 10.0, 4.4)125.45.79 (dt, 10.2, 3.0)121.5
155.74 (d, 10.0)133.36.06 (dt, 10.2, 2.4)129.1
16–92.33.18 (t, 10.2)43.9
17a2.49 (m)29.52.21 (dd, 13.2, 2.4)27.5
17b2.49 (m)2.21 (dd, 13.2, 2.4)
18a3.51 (m)58.82.25 (dd, 14.8, 8.4)45.0
18b3.51 (m)1.32 (br d, 14.4)
19a1.30 (ddd, 14.0, 8.0, 4.0)37.33.69 (d, 8.4)71.9
19b1.21 (dd, 14.0, 8.0, 6.8)
20–40.4–41.5
212.70 (s)69.63.49 (s)83.0
11-OCH33.78 (s)55.5
COOCH3–168.8–176.0
COOCH33.76 (s)51.13.76 (s)52.5

a1H measured at 400 MHz and 13C NMR measured at 100 MHz.

b1H measured at 600 MHz and 13C NMR measured at 150 MHz.

Fig. 1: (a) 1H–1H COSY (bold) and HMBC (arrow, H→C) correlations of 1. (b) ROESY correlations of 1.
Fig. 1:

(a) 1H–1H COSY (bold) and HMBC (arrow, H→C) correlations of 1. (b) ROESY correlations of 1.

Fusiformine B (2) was obtained as a light yellow amorphous solid; its molecular formula was assigned as C21H24N2O4 from HR-ESI-MS (m/z = 369.1815, [M+H]+; calcd. 369.1813), with 11 degrees of unsaturation. The DEPT and 13C NMR data (Table 1) of 2 revealed 21 carbon signals, which were classified as 1 methoxy group, 5 methylenes, 9 methines, and 6 quaternary carbon atoms. Detailed analysis of the NMR data of 2 and comparison with those of melodinine L [7] indicated that 2 was 19-hydroxy derivative of melodinine L. The oxygenated methine group (δH = 3.69 ppm, d, J = 8.4 Hz; δC = 71.9 ppm) was assigned as C-19 and was verified by HMBC of H-19 (δH = 3.69 ppm, d, J = 8.4 Hz) with C-2 (δC = 67.3 ppm), C-20 (δC = 41.5 ppm), and C-21 (δC = 83.0 ppm) (Fig. 2a). The coupling constant of H-19 (d, J = 8.4 Hz) and ROESY correlations of H-19 and H-21 indicated a β-OH group at C-19 (Fig. 2b). Detailed analysis of 2D NMR (heteronuclear single-quantum coherence, 1H–1H COSY, HMBC, and ROESY) data confirmed that the other parts were the same as those of melodinine L.

Fig. 2: (a) 1H–1H COSY (bold) and HMBC (arrow, H→C) correlations of 2. (b) ROESY correlations of 2.
Fig. 2:

(a) 1H–1H COSY (bold) and HMBC (arrow, H→C) correlations of 2. (b) ROESY correlations of 2.

The absolute configurations of 1 and 2 could not be established by comparison of the calculated and experimental electronic circular dichroism (ECD) spectra due to the lack of sufficient amounts of substances. However, the absolute configurations might be identical with those of known compounds from a biogenetic point of view [10, 11].

The cytotoxic activities of 1 and 2 against the growth of human tumor cell lines (HL-60 and A-549) by using the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method were evaluated [12]. The results indicated that 1 showed a moderate cell growth inhibitory activity against all cancer cell lines with IC50 values of 9.80 and 12.38 μm, respectively, while 2 were inactive against the above cancer cells (IC50 > 40 μm).

3 Experimental section

3.1 General experimental procedures

IR spectra were measured with a Bio-Rad FTS-135 spectrometer from KBr pellets. Optical rotations were obtained on a JASCO P-1020 digital polarimeter. UV spectra were recorded on a Shimadzu UV-2401PC. HR-ESI-MS were measured on an API QSTAR Pulsar 1 spectrometer. 1D and 2D NMR spectra were measured on AM-400 spectrometers, using TMS as an internal standard, and chemical shifts were recorded as δ values. Column chromatography was performed on silica gel H (10–40 μm; Qingdao Marine Chemical Ltd. Co.), Sephadex LH-20 (40–70 μm, Amersham Pharmacia Biotech AB, Uppsala, Sweden), and Lichroprep RP-18 gel (20–45 μm; Merck, Darmstadt, Germany).

3.2 Plant material

The twigs and leaves of M. fusiformis were collected in Guizhou Province, People’s Republic of China, in October 2012. The material was identified by Prof. Xiuren Zhou, Henan Institute of Science and Technology, and a specimen (No. 1210010) was deposited at Life School of Science and Technology, Henan Institute of Science and Technology, China.

3.3 Extraction and isolation

The air-dried and powdered twigs and leaves of M. fusiformis (10.0 kg) were extracted with MeOH, and the crude extract was adjusted to pH = 2–3 with saturated tartaric acid. The acidic mixture was defatted with petroleum ether and ethyl acetate. The aqueous phase was basified to pH = 9–10 with saturated NaOH. The aqueous phase was subsequently extracted with CHCl3 to obtain crude alkaloid (80.0 g). The crude alkaloid was subjected to a silica gel column (CHCl3–MeOH, 1:0 to 0:1) to obtain five fractions (I–V). Fr. II (10.0 g) was eluted with petroleum ether–acetone (10:1 to 1:1) and was further subjected to a Sephadex LH-20 column eluted with MeOH to afford 1 (23.0 mg). Fraction III (14.8 g) was subjected to a Sephadex LH-20 column eluted with CHCl3–MeOH (1:1) and subsequently a series of silica gel columns eluted with CHCl3–acetone (20:1 to 5:1) to give 2 (18.0 mg).

3.4 Identification

Fusiformine A (1): Light yellow amorphous solid. – 1H NMR and 13C NMR data (see Table 1). −[α]D25  = –227.7 (c = 0.40, MeOH). – IR (KBr): vm = 3384, 2932, 1675, 1615 cm−1. – UV (MeOH): λ (log ε) = 327 (4.18), 246 (4.09), 207 (4.25) nm. – MS ((+)-ESI): m/z = 383 [M+H]+. – HRMS ((+)-ESI): m/z = 383.1893 (calcd. 383.1893 for C22H26N2O4+, [M+H]+).

FusiformineB (2): Light yellow amorphous solid. – 1H NMR and 13C NMR data (see Table 1). −[α]D25  = –67.5 (c = 0.175, MeOH). – UV (MeOH): λ (log ε) = 295 (3.38), 243 (3.81), 204 (4.38) nm. – IR (KBr): vm = 3441, 2922, 1727 cm−1. – MS ((+)-ESI): m/z = 369 [M+H]+. – HRMS ((+)-ESI): m/z = 369.1815 (calcd. 369.1813 for C21H25N2O4+, [M+H]+).

Corresponding author: Yong-chao Li, School of Life Science and Technology, Henan Institute of Science and Technology, Xinxiang 453003, P.R. China, e-mail:

Acknowledgments

This research was financially supported by Industry, Education, and Academy Program of Henan province (1421070000229).

References

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Received: 2015-3-25
Accepted: 2015-4-30
Published Online: 2016-1-30
Published in Print: 2016-3-1

©2016 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. In this Issue
  3. Review
  4. Cerium intermetallics CeTX – review III
  5. Fusiformines A and B: new indole alkaloids from Melodinus fusiformis
  6. Preparation, crystal structure, thermal behavior, and theoretical studies of N,N′-dinitro-4, 4′-azo-bis(1,2,4-triazolone) (DNZTO)
  7. Design, synthesis, and biological evaluation of new series of 2-amido-1,3,4-thiadiazole derivatives as cytotoxic agents
  8. One-pot hydrothermal synthesis of H3PW12O40 supported on zeolite imidazolate frameworks (ZIF-8): a highly efficient heterogeneous catalyst for oxidation of sulfides to sulfoxides and sulfones
  9. Catalytic performance of a Keplerate-type, giant-ball nanoporous isopolyoxomolybdate as a highly efficient recyclable catalyst for the synthesis of biscoumarins
  10. Thermal behavior of benzobis(tetraethyldisilacyclobutene)
  11. Synthesis and crystal structures of three novel benzimidazole/benzoindolizine hybrids
  12. NQR and X-ray crystal structure studies of cadmium halide complexes: [C(NH2)3]CdI3 and [4-ClC6H5NH3]3CdBr5
  13. Phosphanchalkogenide und ihre Metallkomplexe. IV. Halogenierungsprodukte der Gold(I)halogenidkomplexe einiger Diphosphanmonochalkogenide
  14. Note
  15. Synthesis of aminomethyl derivatives of 5-substituted-3-(prop-2-ynyl)dihydrofuran-2(3H)-ones
https://doi.org/10.1515/znb-2015-0052
Keywords for this article
fusiformine A; fusiformine B; Melodinus fusiformis; monoterpenoid indole alkaloids

Articles in the same Issue

  1. Frontmatter
  2. In this Issue
  3. Review
  4. Cerium intermetallics CeTX – review III
  5. Fusiformines A and B: new indole alkaloids from Melodinus fusiformis
  6. Preparation, crystal structure, thermal behavior, and theoretical studies of N,N′-dinitro-4, 4′-azo-bis(1,2,4-triazolone) (DNZTO)
  7. Design, synthesis, and biological evaluation of new series of 2-amido-1,3,4-thiadiazole derivatives as cytotoxic agents
  8. One-pot hydrothermal synthesis of H3PW12O40 supported on zeolite imidazolate frameworks (ZIF-8): a highly efficient heterogeneous catalyst for oxidation of sulfides to sulfoxides and sulfones
  9. Catalytic performance of a Keplerate-type, giant-ball nanoporous isopolyoxomolybdate as a highly efficient recyclable catalyst for the synthesis of biscoumarins
  10. Thermal behavior of benzobis(tetraethyldisilacyclobutene)
  11. Synthesis and crystal structures of three novel benzimidazole/benzoindolizine hybrids
  12. NQR and X-ray crystal structure studies of cadmium halide complexes: [C(NH2)3]CdI3 and [4-ClC6H5NH3]3CdBr5
  13. Phosphanchalkogenide und ihre Metallkomplexe. IV. Halogenierungsprodukte der Gold(I)halogenidkomplexe einiger Diphosphanmonochalkogenide
  14. Note
  15. Synthesis of aminomethyl derivatives of 5-substituted-3-(prop-2-ynyl)dihydrofuran-2(3H)-ones
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