Monotetrahydrofuran annonaceous acetogenins from the seeds of Annona squamosa

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Abstract

Three new monotetrahydrofuran annonaceous acetogenins, Annosquamins A–C (1–3) were isolated from the 95% EtOH extract of Annona squamosa seeds, in addition to the known compounds, solamin, annotemoyin-1, uvariamicin-II, uvariamicin-III. Their structures were elucidated by spectroscopic analysis and the relative configurations of bearing tetrahydrofuran rings were established by comparing NMR data with model compounds.

Graphical abstract

Three new monotetrahydrofuran annonaceous acetogenins, Annosquamins A–C (1–3) were isolated from the 95% EtOH extract of Annona squamosa seeds, in addition to the known compounds, solamin, annotemoyin-1, uvariamicin-II, uvariamicin-III. The differences among these natural compounds are the position or stereochemistry of the THF ring with two flanking hydroxyl groups.

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Highlights

► This study reports on the isolation of seven monotetrahydrofuran annonaceous acetogenins from Annona squamosa seeds. ► Structure elucidation were made based on NMR and mass spectroscopic analyses. ► Three of them are new annonaceous acetogenins.

Introduction

More than 224 monotetrahydrofuran annonaceous acetogenins (mono-THF ACGs) were isolated so far. They exhibit a broad range of biological properties, such as cytotoxic, immunosuppressive, pesticidal, antiparasitic and antimicrobial activities (Bermejo et al., 2005, Pettit et al., 2008, Eparvier et al., 2006, Liaw et al., 2004a, Liaw et al., 2008). Especially, their potential to inhibit tumor cells that are multiple drug resistant (MDR) has attracted increasing interest. The total content of ACGs in the seeds of Annona squamosa was higher than in other four species (A. glabra, A. muricata, A. reticulate and A. bullata) (Yang et al., 2009a). We have reported the isolation of two novel cytotoxic acetogenins from the seeds of A. squamosa and the investigation of the structure–activity relationships of diverse ACGs (Yang et al., 2009b, Yang et al., 2009c). Mechanism of actions studies have shown that ACGs are the most potent inhibitors of mitochondrial respiratory chain complex I. In the absence of a structural model of inhibitor binding site of complex I, it is very difficult to predict the inhibitory potency of a new acetogenins (Bermejo et al., 2005). In this study, as a part of our continued structural–activity investigation of ACGs, seven monotetrahydrofuran acetogenins, three of which are new annonaceous acetogenins, were isolated from the 95% EtOH extract of A. squamosa seeds. The differences among these natural compounds are the position or stereochemistry of the THF ring with two flanking hydroxyl groups.

Section snippets

Results and discussion

Annosquamin A (1) was isolated as a white powder (Fig. 1), with the molecular formula C35H64O5 by HRESIMS (m/z 587.4576 [M+Na]+, calcd 587.4651 and 565.4896 [M+H]+ calcd 585.4832), indicating 4 degrees of unsaturation. The IR absorption at 3428 and 1741 cm−1, the UV maximum at 220 nm, and a positive reaction to Kedde's reagent implied the presence of an α,β-unsaturated γ-lactone. The proton signals in the 1H NMR spectrum (Table 1) at δH 6.97 (1H, d, J = 1.5 Hz, H-33), 4.99 (1H, qd, J = 7.0, 1.5 Hz,

General experimental procedures

Melting points were determined on a YanacoMP-S3 micro melting point apparatus and are uncorrected. Optical rotations were measured on a Perkin-Elmer 241 MC polarimeter. The UV spectra were taken on a HP 8451A diode array spectrophotometer. IR spectra were recorded on a NEXUS-470 spectrophotometer. 1D and 2D NMR spectral data were recorded on Brucker ACF-300P or Brucker ACF-500P spectrometers in CDCl3. Exact masses (HRESIMS) were measured by a Waters Synapt HDMS system. Chromatography was

Supplementary data

Supplementary data (HRESIMS, 1H and 13C NMR spectra of compounds 1–3 and known compound data).

Acknowledgments

This work was supported by grants from Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica (P09018), the Science and Technology Program of Jiangsu Administration of Traditional Chinese Medicine (LZ09001), the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (ysxk-2010), Doctoral Fund of Ministry of Education of China and Program sponsored for scientific innovation research of college graduate in Jiangsu

References (20)

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