Hydrogen-bonded rotamers of 2′,4′,6′-trihydroxy-3′-formyldihydrochalcone, an intermediate in the synthesis of a dihydrochalcone from Leptospermum recurvum
Introduction
As an extension of our studies on the bioactive components of the New Zealand manuka, Leptospermum scoparium,1., 2. we have screened Leptospermum species for a range of biological activities. This study revealed that the ethanol extract of the foliage of Leptospermum recurvum Hook. f. (family Myrtaceae) possessed antiviral activity. This plant, endemic to Mt Kinabalu in the States of Sabah, Malaysia has been reported to contain the polyphenols, cyanidin, quercetin, ellagic acid, delphinidin and myricetin,3 but we could find no reports on medicinal properties. However, L. recurvum is almost identical (apart from leaf size) to L. flavescens3 which has been used traditionally in Malaysia to stimulate appetite and relieve stomach disorders and menstrual discomfort.4
In this paper we describe the isolation of flavonoid components of L. recurvum foliage, including the dihydrochalcone (1). Synthesis of 1 was subsequently achieved via the formyl derivative (2). NMR studies of 2 produced spectra with some broad peaks and some notable absences of signals. Searching the literature likewise revealed incomplete sets of NMR data. We here detail studies of the solution chemistry of 2, by low temperature NMR and by molecular mechanics and ab initio studies, that elucidate the conformational exchange responsible for these anomalies.
Section snippets
Results and discussion
The dried foliage of L. recurvum was extracted with ethanol and, after repeated column chromatography and preparative TLC on silica gel, yielded 2′,4′,6′-trihydroxy-3′-methyldihydrochalcone 15 and an inseparable mixture of 2,5-dihydroxy-6-methyl-7-methoxyflavanone (3) and its isomer 2,5-dihydroxy-8-methyl-7-methoxyflavanone (4).6 Further components proved difficult to separate from the major component, the mixture of hydroxyflavanones 3 and 4. This mixture was dehydrated to convert 3 and 4 to
Conclusions
Although dihydrochalcone 7, flavanones 3, 4 and 8 and flavone 5 have all been reported from natural sources, this is the first report of dihydrochalcone 1 as a natural product. These flavonoids are unusual in that they have C-methylated A-rings and non-oxygenated B-rings. Synthesis of 1 has confirmed the cytotoxicity observed for the natural sample.
The complex NMR spectra of formyl dihydrochalcone 2 have been demonstrated to arise from conformational exchange between hydrogen-bonded rotamers.
General
UV and IR spectra were recorded on a Jasco 7800 UV–Vis spectrometer and a Perkin–Elmer 1600 FTIR instrument respectively. Melting points were determined on a hot bench Leica AG melting point apparatus first calibrated with standard samples of known melting points. NMR spectra were recorded on a Varian INOVA-500 spectrometer operating at 500 MHz for 1H and 125 MHz for 13C NMR spectra were recorded on ca. 0.075 M solutions in d6-acetone (referenced to solvent, δ 2.05 for 1H and δ 29.9 for 13C) or
Acknowledgements
Thanks to W. Harris and J. W. van Klink for plant material, M. Thomas and W. Redmond for assistance with NMR experiments, B. Clark for MS analysis; G. Ellis for biological assays, and M. Dick for microanalysis. This research was supported in part by the New Zealand Foundation for Research, Science and Technology and by the New Zealand Official Development Assistance (NZODA), Ministry of Foreign Affairs and Trade (PhD scholarship).
References (27)
- et al.
Phytochemistry
(1997) - et al.
Phytochemistry
(1978) - et al.
Phytochemistry
(1997) Phytochemistry
(1990)- et al.
Phytochemistry
(1995) - et al.
Phytochemistry
(1991) - et al.
Phytochemistry
(1992) - et al.
J. Nat. Prod.
(1999) - et al.
J. Linn. Soc.
(1980) Maori Healing and Herbal
(1994)
Eur. J. Org. Chem.
Acta Pharm. Nord.
Magn. Reson. Chem.
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