Monoterpenoid phloroacetophenones from Euodia latifolia

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(C-l’), 128.7 (C-3’ and S), 128.3 (C-4’), 125.7 (C-2’ and 6’), 123.0 (C-6), 83.3 (C-3a), 78.5 (C-2), 78.4 (C-3), 67.7 (C-7a); EIMS m/z: 232 (M, 8%), 126 (7), 122 (12), 107 (28), 105 (22), 97 (IOO), 95 (36), 91 (14), 77 (25); IR vzf,c’a cm - ‘: 3500 (br), 3030 (m), 2980 (s), 2920 (m), 2860 (m). 1730 (vs.), 1645 (w), 1600 (w), 1380 (m). 1250 (m), 1120 (s). X-Ray difiaction data. C,,H,,O,, M,=232.2, monoclinic, space group P2, (C:, No. 4), cr = 8.476 (2), h = 6.105 (9), c = i0.955 (6) 8, /I= 109.70 (3)-, CI = 533.7 A3. D, (Z = 2) = I .44 g/cm”. F(OO0) = 244. R,R, = 0.041, 0.042 for 877 ‘observed’ reflections [I <30(I)] out of 1036 independent reflections to 20,,,= 50 ‘. Enraf-Nonius CAD-4 diffractometer, monochromatic MoK, radiation. 20/O scan. i. ~0.7106, A, p = 0.7 cm I. Specimen: 0.17 x 0.65 x 0. I 1 mm. Anisotropic thermal parameter refinement for C, 0; (x, )‘, z, U,& refined (full matrix least squares). Hydrogen atom and thermal parameters, and structure factor amplitudes available from the Editor and/or Cambridge Crystallographic Data Centre.

supported by the Network for Biologically Products and UKM (IRPA 4-07-03-05).

5. 6.

8. 9.

Burkhill, I. H. (1966) in A Dictionary ofthe Economic Plants of the M&y Peninsula. p. 1115. Ministry of Agriculture and Co-operatives, Kuala Lumpur, Malaysia. Loder, J. W. and Nearn, R. H. (1977) Heterocycles 7, 113. EI-Zayat, A. E., Ferrigni, N. R., McCloud, T. G., McKenzie, A. T., Bryn, S. R., Cassady, J. M., Chang, C. 1. and McLaughlin, J. L. (1985) Tetrahedron Letters 26, 955. Ueno, Y., Tadano, K.-I., Ogawa, S., McLaughlin, J. L. and Alkofahi, A. (1989) Bull. Chem. Sot. Jpn 62, 2328. -Sam, T. W., Sew-Yeu, C., Matsjeh, S., Can, E. K., Razak, D. and Mohamed, A. L. (1987) Tetrahedron Letters 28, 2541. Gesson, J. P., Jacquesy, J. C. and Mondon, M. (1987) Tetrahedron Letters 28, 3945. Gesson, J. P., Jacquesy, J. C. and Mondon, M. (1987) Tetrahedron Letters 28, 3949. Tadano, K.-l., Ueno, Y. and Ogawa, S. (1988) Chem. Letters 111. Gillhouley, J. G. and Shing, T. K. M. (1988) J. Chem. Sot. Chem. Commun. 976.

003 I 9422/!M $3.00 + 0.00

Phytoi’hemisrr,v, Vol. 29, No. 5. pp. 1704 1706, 1990. Printed in Great Britain.

MONOTERPENOID

iv, 1990 Pergamon Prcsa plc

PHLOROACETOPHENONES LATIFOLIA

S. H. GOH, V. C. CHUNG, Chemistry

Department,

(Receioed

FROM EUODIA

C. K. SHA* and T. C. W. MAK?

University of Malaya, Kuala Lumpur, Taiwan, _FChemistry Department,

Key word Index- Euodiu lut~jblia: Rutaceae bramine; coumarins.

Natural

REFERENCES

7. Acknowledgements-~Dr Lyndsay Byrne (Organic Chemistry Department at the University of Western Australia) is thanked for recording the NMR spectra and Dr John MacLeod (Research School of Chemistry at the Australian National University) is thanked for providing the EIMS. This work was

Important

Malaysia; Chemistry Department, N,ational The Chinese University. Hong Kong

21 September

melifoliones;

Tsing Hua University,

1989)

monoterpenoid

phloroacetophenones;

desbenzylideneru-

Abstract-Extracts of Euodia latifolia provided mainly coumarin derivatives, 5,7,8-trimethoxycoumarin, bergapten, and 6,7&trimethoxycoumarin, and minor amounts of two new natural products which have the tetracyclic monoterpenoid phloroacetophenone skeleton. X-Ray structure determination showed that one of the new products is desbenzylidenerubramin. The spectral data established that the other is an isomer of desbenzylidenerubramin.

INTRODUCTION

Euodia lattjolia, a tall tree found mainly in lowlands, is one of the more common Euodia species of Peninsular Malaysia. Interest in the species is in its alleged medicinal properties; a deco&on of the leaves is used as a remedy for fever and cramps [l]. Interest in the Euodia is also generated in the reclassification of the genera Euodia, Melicope and Tetradium [2. 31. Among the commonly

found Malaysian Euodia, including E. mucrocarpu King, E. pachyphylla King, and E. roxhurghiana (Cham.) Benth. ex Hk. f., the alkaloid content (mainly furoquinolines and pyranoquinolines) indicates that they belong to the new classification of Melicope sensu Hartley. Euodin latfofolia is notable in that it does not provide alkaloids but mainly coumarin derivatives. Additionally two isomeric monoterpenoid phloroacetophenones, melifoliones la and b, isolated in minor amounts, are reported in this paper.

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Table 1. ‘H and 13CNMR spectra of compounds la and b lb

la

la

R’=Ac,

RZ=H

lb

R’=H,

R’=Ac

2

RESULTS AND DISCUSSION

Coumarin derivatives were readily isolated from E. latifolia but furoquinoline alkaloids, found in most other Malaysian Euodia species, were not found in the extracts. In the search for acetophenone derivatives, which are also common in a number of Euodia and Melicope species, two novel monoterpenoid phloroacetophenones, melifoliones la and b were isolated. The ‘H NMR spectra showed that both compounds had characteristic intramolecularly Hbonds (613.32 and 13.63 respectively). Although the methyl absorptions were quite well separated, the other aliphatic proton absorptions were only resolvable with difficulty at 400 MHz. Both compounds showed charac13C NMR absorptions for monoterpenoid teristic phloroacetophenone derivatives, but the nature of the ring structure was not apparent. Compound la readily crystallized and was used for a single X-ray diffraction study. The perspective view of the molecule (Fig. 1) shows a novel tetracyclic monoterpenoid phloroacetophenone derivative. As expected, there is intramolecular H-bonding of the phenolic hyOdrogen to the keto group, the O-O distance being 2.503 A. The six-membered carbon ring is in the chair conformation while both the six-membered dihydropyran rings assume twist-boat conformations. The structure of the compound is that of the quite rare desbenzylidenerubramin which has been isolated from Aniba rosaeodora Ducke [4]. The assignment of this structure allows for the assignment of the isomer lb, the skeleton of which is similar to bruceol(2) from Eriostemon brucei [S]. Although such monoterpenoid phloroacetophenones are quite rare even among plants of the Rutaceae, compound la could be synthesized surprisingly easily from the pyridine-catalysed reaction of phloroacetophenone and citral [6]. Among the Malaysian Euodia species, E. latifolia has relatively larger amounts of monoterpene essential oils, hence making the biosynthesis of melifoliones more likely. Previous work on rubramin indicated that the compound was not optically active; the present melifoliones also had optical activity close to zero. EXPERIMENTAL

Materials and methods. Plant materials were collected from Gunung Bunga Buah, Genting Highlands, Pahang, West Malaysia. Mp: uncorr. ‘H and 13CNMR: 100 (or 400) and 25 MHz, respectively, CDCl,, TMS as int. standard; GCMS or direct

OH Ar-H COMe S-Mea l-Me 8-MeP 3-H 2-H/? 4-H 2-Ha 6-H/9 6-Ha S-Ha 5-H/? c=o Ar

s s s

s s

s br t dt ddd dd : dt ddt S S, S S, S S, d

C-l C-8 c-3 c-2 C-6 c-4 Cl-Me C8-Me, COMe c-5

S

si t

t d 4 4. 4 4 t

13.32 6.04 2.62 1.59 1.37 1.13 2.74 2.20 2.09 1.87 1.82-1.88 1.48 1.31 0.86 202.7 165.3, 163.3 158.8, 106.5 106.3, 98.3 85.0 76.6 45.9 37.7 34.8 32.3 29.6 28.8, 24.2 27.4 22.0

-

13.63 6.01 2.62 1.52 1.43 1.10 2.83 2.20 2.05 1.87 1.83-1.88 1.48 1.35 0.87 202.1 164.3, 162.7 159.4, 107.5 106.4, 96.9 86.6 76.0 46.2 37.5 34.8 32.0 29.9 28.6, 24.3 27.5 21.8

probe EIMS: Kratos MS3074 mass spectrometer with a DS55 data system. Extraction. Dried leaves (700 g) of E. latifdia were extracted ( x 2) with 2 1 EtOH and the extracts evapd in uacuo to give a gummy residue. Trituration with a little MeOH and evapn under red. pres. gave 30 g of residue. Chromatography of 15 g of this extract in CHCl, through 100 g silica gel 60 (70-230 mesh) with CHCl, elution gave an essential oil fraction (O.l%), a fraction containing melifoliones la and b (0.006%) and bergapten (0.02%). Further elution by MeOH-CHCl, (1:49) 5,7,8-trimethoxycoumarin (0.1%) and 6,7,8-trimethoxycoumarin (0.002%) and sterols (0.006%). The sterols (analysed on a 6’ 3% OVl/Gas Chrom Q glass column) were found to be sitosterol, stigmasterol and campesterol in the ratio 62: 17:21. Melifoliones were further purified by prep. silica gel TLC with CHCl,-hexane (7: 3) with both isomers having R, Ct.43(ratio of isomers 1a:lb is 3:2 by ‘H NMR). Fractional crystallization gave first almost colourless rods of la and then needles of lb. The isomers could only be partially resolved on the above GC column. Melifolione la. Mp 138-140” (ref. [4] for desbenzylidenerubramine 140”). Rod-shape crystals were suitable for single crystal X-ray diffraction. MS m/z (rel. int.): 302.158 [M]’ (24; C 18H 220 4 requires 302.162), 287 (5) and 219 (100); IR vkE[3400 (broad) and 1600 cm-’ (strong); UV~~:~” (E):235 (11350), 293 (12800) and 335 nm (2110); ‘H and 13CNMR: Table 1. Melifolione lb. Mp 158-159”, MS similar to la The NMR spectral characteristics (Table 1) are quite distinct from la described above. UV I:,$‘” (E): 337.0 (2640), 292.0 (21400), 235.0 nm (17 700).

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Bergapten. Needles (MeOH), mp 187-188” (lit. [7] 18X-189”). correct ‘H and 13C NMR spectra. 5,7,X-Trimetl~l,r~coumarin. Needles (MeOH). mp 180-181’ (ref. [X] 175 ), correct ‘H and “CNMR spectra. 6,7,X-~rimrrkox~coumurin. Crystals (petrol 6&80’-Et,O) mp. IO?- 104 (ref. [X] 104’ j. The structure is supported by ‘H and ‘lC NMR spectra. Crystal darufijr la. C,RH2204, M, 302.37, monoclinic, space group P2,,‘c (No. 14). u=9.936(2), h= 11.566(l), c= 14.138(2), fi 2=4, D,=1.280gcm--‘, =105.11(l) , L’=156X.6(4).&3, /I(MoK,)= 0.X4 cm- ‘, F(OO0) =64X. Intensities were measured at 20 on a Nicolet R3m;V diffractometer with graphite-monochromatized MoK, radiation (i. =0.71073 A). w scan mode (20,,, = 55 , scan rate 2.02-x.37 degimin), using a crystal ofdImensions 0.46 x 0.40 x 0.40 mm. Empirical absorptions corrections (transmission factors 0.958 to 0.997) were applied, and of the 3062 umque reflections measured, 2321 observed data with I > 30(I) were used for structure analysis. All non-hydrogen atoms were refined anisotropically, and the aromatic, methine, and methylene H atoms allowed to ride on their respective parent C atoms with assigned isotropic temperature factors. The hydroxyl H atom w’as located in a difference map and included in structurefactor calculations with an assigned isotropic temperature factor. The weighting function w= [0Z(F,)+0.0008)F,~Z] 1was used in full-matrix least-squares refinement, leading to R, =0.072 for 199 variables. The final difference map contained residual extrema at + 0.34 to -- 0.40 eA m3. Computations were performed with the SHELXTL-PLUS package on a DEC MicroVAX-II system. Atomic co-ordinates, bond length and angles, and thermal parameters have been deposited at the Cambridge Crystallographic Data centre. A perspective view of the molecule is shown in Fig. 1.

Acknowledyements~ --We thank AEECP for financial assistance.

the University

of Malaya

and

Fig. 1. X-Ray structure

of compound

la.

REFERENCES

1. Perry, L. M. and Metzger, J. (1980) in Medicinal Plants qf‘East and Southeast Asia: Attributed Properties and Uses. MIT Press, Cambridge. 2. Hartley, T. G. (1981) Card. Bull. Singapore 34, Y1. 3. Ng, K. M., But, P. Pui-Hay, Gray, A. I., Hartley, T. G., Kong, Y. C. and Waterman, P. G. (1987) Biochem. Sq‘st. Ecol. 15,587. 4. Combes, G., Vasssort, Ph.. and Winternitz, F. (1970) Tetrahedron 26, 5981. Duffield, A. M., Jefferies, P. R., Maslen. E. N. and Rae, A. 1. M. (1963) Tetrahedron 19, 593. Kane, V. V. and Grayeck. T. L. (1971) Tetrahedron Letrers 43, 3991, Dean, F. M., Costa, A., Harborne, J. B., and Smith, D. M. (1971) Phytochemistry 17, 505. Devon, T. K. and Scott, A. I. (1972) Norural/)> Occurring Compounds Vol. 1. Academic Press, New York.