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Journal of Asian Natural Products Research

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A novel 1,10-seco withanolide from Physalis peruviana

Sheng-Tao Fang
a a b

, Ji-Kai Liu & Bo Li

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650204, China
b

Graduate School of the Chinese Academy of Sciences, Beijing, 100039, China Available online: 13 Jul 2010

To cite this article: Sheng-Tao Fang, Ji-Kai Liu & Bo Li (2010): A novel 1,10-seco withanolide from Physalis peruviana , Journal of Asian Natural Products Research, 12:7, 618-622 To link to this article: http://dx.doi.org/10.1080/10286020.2010.482523

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Journal of Asian Natural Products Research Vol. 12, No. 7, July 2010, 618622

NOTE A novel 1,10-seco withanolide from Physalis peruviana

Sheng-Tao Fangab, Ji-Kai Liua and Bo Lia*
a

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China; bGraduate School of the Chinese Academy of Sciences, Beijing 100039, China (Received 28 December 2009; nal version received 29 March 2010)

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A novel 1,10-seco withanolide, 1,10-seco withaperuvin C (1), together with four known withanolides, 4b-hydroxywithanolide E (2), visconolide (3), withanolide F (4), and withaphysanolide (5), was isolated from the aerial parts of Physalis peruviana. The structures of compounds 1 5 were determined on the basis of spectroscopic methods including extensive 1D and 2D NMR analysis. In addition, the possible biogenetic relationships among these ve withanolides are discussed. Keywords: Physalis peruviana; 1,10-seco withaperuvin C; withanolide; steroid

1.

Introduction

2.

Results and discussion

The genus Physalis (Solanaceae) includes about 120 species mainly distributed in South and North America. Five species of this genus are found in China [1]. Physalis peruviana is a common plant in China, and its fruit is edible, called cape gooseberry. It is also a medicinal plant widely used in folk medicine for treating diseases such as malaria, asthma, hepatitis, dermatitis, diuretics, and rheumatism [2,3]. In previous studies, a series of withanolides had been isolated from this plant [4 12]. In this paper, we report the isolation and elucidation of a new 1,10-seco withanolide, 1,10-seco withaperuvin C (1), together with four known withanolides: 4b-hydroxywithanolide E (2) [13,14], visconolide (3) [15], withanolide F (4) [16], and withaphysanolide (5) [14] from the aerial parts of P. peruviana (Figure 1). Compound 1,10-seco withaperuvin C (1) is the rst example of steroids with a unique 1,10-seco withanolide skeleton isolated from the genus Physalis.
*Corresponding author. Email: [email protected]
ISSN 1028-6020 print/ISSN 1477-2213 online q 2010 Taylor & Francis DOI: 10.1080/10286020.2010.482523 http://www.informaworld.com

Compound 1 was isolated as a white amorphous solid, and showed a quasimolecular ion peak [M Na] at m/z 509 in its positive ESI-MS. Its molecular formula was established as C28H38O7 by HR-ESI-MS at m/z 509.2520. The IR spectrum showed strong absorptions at 3424 and 1708 cm 21, indicating the presence of hydroxyl and ester groups. The 1H NMR and 13C NMR spectra of 1 showed the presence of 28 carbons consisting of two carbonyls, three carbon carbon double bonds including two four-substituted and one-disubstituted, four quaternary carbons including three oxygen-bearing functional groups, four sp3 methines including two oxygen-bearing functional groups, seven methylenes, and ve methyls. Comparison of the NMR spectral data of 1 with those of the known withaperuvin C [17] indicated that compound 1 is also a withanolide derivative, and they have the same substituent patterns and relative congurations in

Journal of Asian Natural Products Research

28 23 21 18 12 11 19 10 4 3 2 1 5 9 13 14 24 25 22 26 27

619

OH
20 17

O OH
16 15

O OH O OH O
2 3 1 4 19 9

OH O O H H R 4 R=H 5 R=OH OH O OH O

H
8

H O O

OH
7

H OH
7

10 8 H 5 6

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O OH 2 R=H 3 R=OH

Figure 1. Structures of compounds 1 5.

rings C, D and in their respective lactone ring, except for the major differences in the A/B rings. In the 1H NMR spectrum, the signals at dH 3.84 (br d, J 17.3 Hz), 3.18 (dd, J 17.3, 8.7 Hz), 5.45 (br dd, J 11.4, 8.7 Hz), and 6.55 (dd, J 11.4, 3.2 Hz) were assigned to H-2a, H-2b, H-3, and H-4, respectively, on the basis of an analysis of the 1H 1H COSY spectrum, and the downeld chemical shift at dH 1.79 (3H, s) implied that Me-19 was a vinylic methyl. In addition, a signal at dH 5.15 (1H, br s, H-6) together with the signal at dC 173.0 (C-1) in the 13C NMR spectrum indicated that 1 possesses a 1,10-seco withanolide skeleton [19]. This was

conrmed by the analysis of the HMBC spectrum, in which long-range correlations were observed between C-1 and H-2b, H-3 and H-6, between H-4 and C-5, C-6, and C-10, and between C-5 and Me-19, as shown in Figure 2. Therefore, a sevenmembered b, g-unsaturated lactone moiety was considered in ring A. The b-conguration of the lactone bond at C-6 was established by a ROESY experiment (Figure 2). The ROESY spectrum showed the correlation between H-6 (d 5.15, br s) and H-2a, H-7a and H-7b, indicating that H-6 has the same conguration as H-2a. Since a small coupling between H-2a and H-3 in the

OH O OH
19 10 9

H H
8

OH H O O HMBC ROESY

H
3

O5
1 2

O
7 6

H H

Figure 2. The key HMBC and ROESY correlations of compound 1.

620
1

S.-T. Fang et al. were measured on a Bio-Rad FTS-135 spectrometer. 1D and 2D NMR spectra were recorded on a Bruker AM-400 and DRX-500 instruments with TMS as an internal standard. ESI-MS and HR-ESIMS were measured on VG AutoSpec-3000 and API Qstar-Pulsar LC/TOF mass spectrometers. Column chromatography (CC) was performed over silica gel (200 300 mesh; Qingdao Marine Chemical Inc., Qingdao, China). TLC was performed on precoated silica gel G plates (Qingdao Marine Chemical Inc.), and spots were visualized by spraying with 10% H2SO4 in EtOH, followed by heating.

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H NMR spectrum was observed due to an approximate 908 dihedral angle between them, a b-conguration of the lactone bond at C-6 was inferred, which is in agreement with those of stoloniolide I [18] and 1,10-seco withametelin B [19]. Therefore, the structure of 1 was deduced as shown in Figure 1, which was named 1,10seco withaperuvin C. In addition to the new 1,10-seco withanolide 1, four known withanolides 2 5 were isolated from the aerial parts of P. peruviana. The possible biogenetic relationships among these ve compounds are discussed in Scheme 1.

3.

Experimental

3.1 General experimental procedures Optical rotations were determined on a Horiba SEPA-300 spectropolarimeter. UV spectra were recorded on a Shimadzu UV2401PC spectrophotometer. IR spectra
O [O] O

3.2 Plant material The aerial parts of P. peruviana were collected from Kunming, Yunnan Province, China, in September 2005, and were identied by Prof. Chengmin Zhang, Kunming Institute of Botany. A voucher

4 [O] O [O] O withanolide E ROH O X

OH 5

O [O] (3) O OH 2

RO RO O RO O O

O X

O O 1

Scheme 1. Possible biogenetic relationships of compounds 1 5.

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Table 1. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectral data for compound 1 in CDCl3 (d in ppm, J in Hz). Position 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

621

dH
3.84 (br d, J 17.3) a-H, 3.18 (dd, J 17.3, 8.7) b-H 5.45 (br dd, J 11.4, 8.7) 6.55 (dd, J 11.4, 3.2) 5.15 2.04 2.05 2.57 (br s) (m), 1.81 (m) (m) (m)

dC
173.0 35.6 116.7 129.3 124.1 73.8 29.5 36.9 39.5 143.4 25.5 31.1 55.0 82.0 37.1 37.9 87.5 21.2 15.7 78.9 19.6 79.7 34.3 151.0 121.2 166.1 12.3 20.6

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fractions (1 11). Fraction 8 was separated by repeated CC on silica gel, eluting with CHCl 3 MeOH (30:1 15:1) and petroleum ether Me2CO (4:1 2:1) to afford 1 (10 mg) and 4 (234 mg). Fraction 6 provided 2 (425 mg) and 5 (34 mg) after being chromatographed over silica gel, eluting with petroleum ether Me2CO (3:1 2:1). Fraction 10 was subjected to a silica gel column with gradient elution (petroleum ether Me2CO 10:1 1:1), followed by repeated CC to obtain 3 (16 mg).

2.00 (m), 1.43 (m) 2.39 (m), 1.43 (m) 1.79 (m), 1.67 (m) 2.77 (m), 1.50 (m) 1.13 (s) 1.79 (s) 1.43 (s) 4.86 (dd, J 12.2, 4.0) 2.54 (m)

3.3.1

1,10-seco withaperuvin C (1)

76.1 A white amorphous solid; [a ]22.8 D (c 0.18, CHCl3); UV (CHCl3) lmax (log 1) nm: 242 (3.93); IR (KBr) nmax (cm21): 3424, 2923, 1708, 1388, 1288, 1137, 1088, 995; 1 H and 13C NMR spectral data: see Table 1; ESI-MS: m/z 509 [M Na]; HR-ESI-MS: m/z 509.2520 [M Na] (calcd for C28H38O7Na, 509.2515).

Acknowledgements
The authors are grateful to the members of the analytical group for the spectral measurements in the Laboratory of Phytochemistry, Kunming Institute of Botany, Chinese Academy of Sciences.

1.87 (s) 1.94 (s)

specimen (No. 20050911) is deposited in the State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences. 3.3 Extraction and isolation The air-dried aerial parts (6.0 kg) of P. peruviana were extracted with MeOH at room temperature (4 40 liters). The extracts were combined and concentrated, and the residue was suspended in H2O, and then successively partitioned with petroleum ether, CHCl 3, and n-BuOH, respectively. The CHCl3-soluble extract (33 g) was subjected to CC (silica gel; CHCl3 MeOH 100:0 80:20) to afford 11

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