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Biphenylneolignans from wood of Eurycoma longifolia
Phytochetistry,Vol. 31, No. 11, pp. 3993-3995, 1992 Printedin Great Bntam.
BIPHENYLNEOLIGNANS
003 l-9422/92 $5.00 + 0.00
G?J 1992PergamonPress Ltd
FROM WOOD OF EUR YCOMA
HIROSHI MORITA, ETSUKO KISHI,
KOICHI
LONGIFOLIA
TAKEYA and HIDEJI ITOKAWA*
Department of Pharmacognosy, Tokyo College of Pharmacy, Horinouchi 1432-1, Hachioji, Tokyo 192-03, Japan (Receiued in revised form
16 April 1992)
Key Word Index--Eurycoma Ion&o&; Simaroubaceae; wood, biphenylneolignan; biphenyl ether; biphenyl.
Abstract-Two novel isomeric 2,2’-dimethoxy-4-(3-hydroxy-l-propenyl)-4’-(1,2,3-trihydroxypropyl) diphenyl ethers, and two novel biphenyls, 2-hydroxy-3,2’,6’-trimethoxy-4’-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-l-propenyl)biphenyl and 2-hydroxy-3,2’-dimethoxy-4’-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)biphenyl, were isolated from the wood of Eurycomn Zongifo2ia and their structures characterized by spectroscopic means.
INTRODUCTION
H”%,“Qo*oH
A number of simaroubaceous plants have been extensively examined for quassinoids possessing cytotoxic, antitumour and antimalarial activities [1, 21. During a survey of bioactive components of Eurycoma longifolia (Simaroubaceae), which is one of the famous folk medicines of south east Asia, we have already reported the structures and cytotoxic activities of various quassinoids [3], squalene-type triterpene ethers [4, 51, and tirucallane-type triterpenes 16-J.Further research on the chemical constituents of this species led us to the isolation of four novel biphenylneolignans 1-4. Herein, we describe their isolation and structural elucidation.
Mcb
dhle
1 and2
HO
RESULTSAND DISCUSSION
The methanol extract of the wood of E. longifoEia was fractionated by partitioning between methylene chloride and water. The methylene chloride fraction was purified by successive silica gel, medium pressure LC and high pressure LC to give four biphenylneolignans (l-4). Compounds 1 and 2, possessing the same molecular formulae, &H,,O,, were obtained as yellow needles. Their physical data were different from each other (I: mp 56-58”, [crlD + 1.3”; 2: mp W-62”, [crlr, - 2.5”), but they had similar spectroscopic properties. The ‘H NMR spectrum of 1 suggested the presence of two 1,2,4&substituted benzene rings, two methoxyl groups attached to the aromatic rings, a trans-olefin and four hydroxyl groups, two of which were primary, the others secondary. The 13CNMR spectrum of 1 also indicated the presence of these groups. Furthermore, three hydroxyl groups were revealed to be located successively from C-7’ to C-9’ and another primary one was an allylic alcohol by means of proton coupling sequences in the ‘H-‘H COSY spectrum. Another oxygen atom must be sited between the two aromatic rings because of the molecular formula and 13C chemical shifts at C-l and Cl’. These substituted aromatic ring systems were determined by the COLOC spectrum monitoring/ ‘H-13C *Author to whom correspondence should be addressed.
3: R=OMe 4. R=H
long range couplings and the presence of NOES between H-3 and OMe-2, and between H-3’ and OMe-2’. The NMR data of 2 were quite similar to those of 1. However, the chemical shifts of H-9’ and C-8’ were slightly different from one another. This difference was considered to be due to the different configuration at C-8’. Therefore, the structures of compounds I and 2 were elucidated to be 2,2’-dimethoxy+(3-hydroxyl-propenyl)-4’-(1,2,3-trihydroxypropyI)biphenyl ethers, which were stereoisomeric. Compounds 3 and 4 were obtained as yellow needles (mp 3: 68-70”, 4: 65-66”) and the molecular formulae C,,H,,O, (3) and CaoH,,O, (4) were determined by HRmass spectra. The ‘H NMR spectrum of 3 suggested the presence of two sets of four substituted benzene rings, one of which was symmetrical, three methoxyl groups and an allylic alcohol similar to 1 and 2. The 13C signals at 6 54.7 (d) and 64.1 (6) indicated the presence of an epoxide as a terminal moiety. A hydroxyl group was deduced to be substituted at C-7’ by the proton coupling sequence.
3993
3994
H. MORITAet al. Table
1. ‘HNMR
spectral
data of l-4
from Eurycoma
H
1
2
3 4 5
7.59 (d. J = 2.0)
7.59 (d. J = 1.7)
7.38 (dd, J = 8.0, 2.0)
7.42 (dd, J = 7.8, 1.7)
6 7 8 9 OMe-2 OMe-3 3’ 5’ 6 7 8’
7.24 6.85 6.55 4.56 3.74 -7.14 7.04 7.37 5.60 5.03
9’
4.41 (dd, J = 11.8, 3.8) 4.55 (dd, J = 11.8, 5.4) 3.72 (s) -
OMe-2’ OMe-6’
(d. J = 8.0) (d, J = 15.9) (dt, J = 15.9, 5.3) (d, J = 5.3) (s)
7.27 6.89 6.58 4.58 3.75
(d, J = 7.8) (d, J = 15.8) (dt, J = 15.8, 5.2) (d, J = 5.2) (s)
(d, J= 1.9) (dd, J = 8.3, 1.9) (d, J = 8.3) (d, J=5.1) (br ddd, J=4.9, 4.9, 4.9)
7.19 7.07 7.50 5.60 4.98
(d, J= 1.2) (dd, J = 8.3, 1.2) (d, J = 8.3) (d, J = 5.7) (br ddd, J=5.6, 5.6, 5.6)
3
4
7.15 (s)
7.14 (s) ._
7.33 6.91 6.57 4.59
7.32 6.91 6.57 4.59
(s) (d, J= 15.9) (dt, J= 15.9, 5.3) (d, J= 5.3)
3.58 7.32 7.22 1.22 6.08 3.97 6.2) 4.22 4.27 3.66 _-.
(s) (s) (s) (s) (d, J=6.7) (br ddd, J=6.2,
(s) (d, J = 15.9) (dt, J= 15.9, 5.3) (d. J= 5.3)
3.86 (s) 7.10 (s) 7.10 (s) 6.11 (d, J=7.0) 4.08 (br ddd, J=6.2,
4.11 (dd, J=11.8, 5.7) 4.40 (dd. J = 11.8, 3.6) 3.78 (s) __
The aromatic substitution pattern was determined by HMBC [7] correlations and the hydroxyl group was found to be at C-2. This structure was corroborated by the NOES between OMe-3 and H-4 and between OMe-2, OMe-6’ and H-3’, H-5’, and characterized the compound as 2-hydroxy-3,2’,6’-trimethoxy-4’-(2,3-epoxy-l-hydroxypropyl)-5-(3-hydroxyI-propenyl)biphenyl. Comparison of the rH NMR spectrum of 4 with that of 3 showed an aromatic proton in place of a methoxyl group with the disappearance of a symmetrical aromatic ring. The ‘H signals of H-3’, H-5’ and H-6’ characteristic of an ABXtype pattern were observed in methanol-d, (H-3’: 6 6.95, d, J = 1.9 Hz; H-5’: 6 6.82, dd, J = 1.9, 8.1 Hz; H-6’: 6 6.77, d, .I = 8.1 Hz). These results and HMBC correlations enabled the elucidation of the structure of 4 as 2-hydroxy-3,2’dimethoxy-4’-(2,3-epoxy-l-hydroxypropyl)-5-(3-hydroxyl-propenyl)biphenyl. A combination of 2-D NMR techniques, such as ‘H-‘H COSY, 13C-lH COSY, COLOC and HMBC spectra enabled us to make complete ‘H and 13C assignments of l-4 (Tables 1 and 2). The constituents of the families of the Magnoliales, especially the Magnoliaceae [8-121 and Lauraceae [13-181, are characterized by the presence of a series of unusual biphenylneolignans. However, this is the first isolation of biphenylneolignans from the Simaroubaceae.
longifolia (400 MHz, pyridine-d,)
4.26 4.31 3.73 3.73
Table
6.2, 6.2)
(dd, J = 10.8, 6.6) (dd, J= 10.8, 5.3) (s) (s)
(dd, J = 10.7, 6.7) (dd, J= 10.7, 5.5) (s)
2. 13CNMR spectral data of l-4 Eurycoma longifolia (100 MHz, pyridine-d,)
c 1 3 3 4 5 6 7 8 9 OMe-2 OMe-3 1’ 2’ 3’ 4’ 5’ 6’ 7’ 8’ 9 OMe-2 OMe-6’
6.2,
1
2
3
4
147.4 148.4 112.0 134.5 120.6 116.0 129.4 129.7 62.9 55.8
147.5 148.4 111.9 134.0 120.6 116.0 129.4 129.8 62.9 55.8
130.6 148.8 144.9 111.7 131.9 115.9 129.9 129.0 63.0
130.6 148.8 144.9 111.7 131.8 115.9 130.0 128.9 63.0 -
148.7 151.2 110.9 131.9 119.9 117.8 73.6 86.2 61.7 55.9 -
149.2 151.1 110.8 132.0 120.0 117.9 73.4 87.3 61.7 55.9
56.2 137.7 149.3 104.8 132.5 104.8 149.3 88.9 54.7 64.1 56.3 65.3
56.2 148.2 148.8 110.8 133.5 119.7 116.5 88.7 54.7 64.2 55.8
from
EXPERIMENTAL General. Mp: uncorr. ‘HNMR (400 MHz) and *sCNMR (100 MHz) were measured in pyiidine-d, and those of 4 also in methanol-d,, TMS as int. standard. Silica gel CC was carried out on Wakogel C-200 at amounts equivalent to 100 times those of the sample. Each final purification was done with MPLC and HPLC. Plant material. Wood of E. longifolia was collected in Indonesia in May 1990. Identification was made by Dr Kosasih Padmawinata, Natural Sciences, Bandung Institute of Technology, Indonesia. Extraction and isolation. Wood (4.5 kg) was crushed and extracted with hot MeOH. The coned extract was partitioned
between H,O and CH,Cl,. The CH,Cl,-sol. fr. was subjected to silica gel CC using CH,Cl,-MeOH stepwise elution. The fr. eluted with CH,Cl,-MeOH (3: 7) was purified by silica gelMPLC with n-hexane-EtOAc-MeOH (11: 9:2), ODS-MPLC with MeCN-Ha0 (11:29), then finally ODS-HPLC with MeCN-H,O (3 : 7 and 1: 3) to obtain compounds 1 (27 mg), 2 (25 mg), 3 (13 mg) and 4 (37 mg). Compound 1. Yellow needles, mp 56-58”. [n]u + 1.3” (MeOH; c 1.6). EI-MS m/z (rel. int.): 376 ([M] ‘, 10, calcd for C 20H 240 7: 376.1522, found: 376.1504). 206 (loo), 180 (62), 163 (21), 153 (32), 137 (73), 124 (51). 91 (39), 78 (25). 65 (34). UV 22:” (1OgE): 228
Biphenyls
from Eurycoma
(4.40), 259 (4.36), 267 (4.33). IR $$ cm- i: 3450,1520, 1270, 1130, 1030, 860. Compound 2. Yellow needles, mp 60-62”. [alo -2.5” (MeOH; c 1.6). EI-MS m/z (rel. int.): 376 ([Ml’, 8, calcd for C2,,Hz407: 376.1522, found: 376.1507), 358 (4), 206 (27), 180(63), 152 (42), 137 (lOO), 124 (52), 91(98), 78 (51), 65 (SO). UV 2::” (logs): 208 (4.20), 265 (3.92). IR vfi; cm-‘: 3450, 1510, 1270, 1130, 1030,860. Compound 3. Yellow needles, mp 68-70”. [a]n - 2.6” (MeOH; c 0.8). EI-MS m/z (rel. int.): 388 ([Ml +, 100, calcd for C,, H,,O,: 388.1522, found: 388.1558) 370 (96), 356 (32), 339 (32), 222 (64), E’oH (log E): 211 (4.48) 274 (4.04). 167 (76), 115 (36), 92 (60). UV &,,.. IR vz’ cm-‘: 3450. Compound 4. Yellow needles, mp 65-66”. [alo - 9.7” (MeOH; ~0.7). EI-MS m/z (rel. int.): 358 ([Ml’, 82, calcd for C 20H 220 6: 358.1416, found: 358.1744), 340 (lOO), 137 (57), 115 (21), 91 (27). UV 1::” (logs): 222 (4.42) 277 (4.29). IR v=; cm-‘: 3450. ‘HNMR (CD,OD) 6: 6.94 (br s, H-4), 6.96 (br s, H-6), 6.53 (d, J =15.8Hz,H-7),6.22(dt,5=15.8,5.9Hz,H-8),4.19(dd,5=1.3, 5.8 Hz, H-9), 3.86 (s, OMe-3), 6.95 (d, .I= 1.9 Hz, H-3’), 6.82 (dd, J =1.9, 8.1 Hz, H-S), 6.77 (d, 5=8.1 Hz, H-6’), 5.52(d, J=6.3 Hz, H-7’), 3.49 (br ddd, J=6.4, 6.4, 6.4 Hz, H-8’), 3.79 (m, H-9’), 3.85 (m, H-9’), 3.80 (s, OMe-2’). “CNMR (CD,OD) 6: 130.4 (C-l), 149.1 (C-2), 145.5 (C-3), 112.2 (C-4), 132.6 (C-5), 116.2 (C-6), 132.0 (C-7), 127.6 (C-8), 63.9 (C-9), 56.8 (OMe-3), 147.6 (C-l’), 149.3 (C2’), 110.6 (C-3’). 134.5 (C-4’) 119.8 (C-S), 116.5 (C-6’), 89.3 (C-7’) 55.1 (C-8’) 64.9 (C-9’), 56.4 (OMe-2’). REFERENCES
1. Cassady, J. M. and Suffness, M. (1980) in Arqicancer Agents Based ORNatural Product Models, p. 254. Academic Press, New York.
longifolia
3995
2. Chan, K. L., G’Neill, M. J., Phillipson, J. D. and Warhurst, D. C. (1986) PIanta Med. 105. 3. Morita, H., Kishi, E., Takeya, K., Itokawa, H. and Tanaka, 0. (1990) Chem. Letters 749. 4. Itokawa, H., Kishi, E., Morita, H., Takeya, K. and Iitaka, Y. (1991) Tetrahedron Letters 32, 1803. 5. Itokawa, H., Kishi, E., Morita, H., Takeya, K. and Iitaka, Y. (1991) Chem. Letters 2221. Itokawa, H., Kishi, E., Morita, H. and Takeya, K. (1992) Chem. Pharm. Bull. 40, 1053. Bax, A. and Summers, M. F. (1986) J. Am. Chem. Sot. 108, 2094. Sugii, Y. (1930) Yakugaku Zasshi 50, 183. Fujita, M., Itokawa, H. and Sashida, Y. (1972) Chem. Pharm. Bull. 20, 212. 10. Fujita, M., Itokawa, H. and Sashida, Y. (1973) Yakugaku Zasshi 93. 422. 11. El-Feraly, F. S. and Li, W.-S. (1978) Lloydia 41,442. 12. Ito, K., Iida, T., Ichino, K., Tsunezuka, M., Hattori, M. and Namba, T. (1982) Chem. Pharm. Bull. 30, 3347. 13. Holloway, D. M. and Scheinmann, F. (1973) Phytochemistry 12, 1503. 14. De Diaz, A. M. P., Gottlieb, H. E. and Gottlieb, 0. R. (1980) Phytochemistry 19, 681. 15. El-Feraly, F. S., Cheathum, S. F. and Breedlove, R. L. (1983) Lloydia 46, 493. 16. Suarez, M., Bonilla, J., De Diaz, A. M. P. and Achenbach, H. (1983) Phytochemistry 22,609. 17. Chen, F.-C., Lee, J.-S. and Lin, Y.-M. (1983) Phytochemistry 22, 616. 18. El-Feraly, F. S. (1984) Phytochemistry 23, 2329.
BIPHENYLNEOLIGNANS
003 l-9422/92 $5.00 + 0.00
G?J 1992PergamonPress Ltd
FROM WOOD OF EUR YCOMA
HIROSHI MORITA, ETSUKO KISHI,
KOICHI
LONGIFOLIA
TAKEYA and HIDEJI ITOKAWA*
Department of Pharmacognosy, Tokyo College of Pharmacy, Horinouchi 1432-1, Hachioji, Tokyo 192-03, Japan (Receiued in revised form
16 April 1992)
Key Word Index--Eurycoma Ion&o&; Simaroubaceae; wood, biphenylneolignan; biphenyl ether; biphenyl.
Abstract-Two novel isomeric 2,2’-dimethoxy-4-(3-hydroxy-l-propenyl)-4’-(1,2,3-trihydroxypropyl) diphenyl ethers, and two novel biphenyls, 2-hydroxy-3,2’,6’-trimethoxy-4’-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-l-propenyl)biphenyl and 2-hydroxy-3,2’-dimethoxy-4’-(2,3-epoxy-1-hydroxypropyl)-5-(3-hydroxy-1-propenyl)biphenyl, were isolated from the wood of Eurycomn Zongifo2ia and their structures characterized by spectroscopic means.
INTRODUCTION
H”%,“Qo*oH
A number of simaroubaceous plants have been extensively examined for quassinoids possessing cytotoxic, antitumour and antimalarial activities [1, 21. During a survey of bioactive components of Eurycoma longifolia (Simaroubaceae), which is one of the famous folk medicines of south east Asia, we have already reported the structures and cytotoxic activities of various quassinoids [3], squalene-type triterpene ethers [4, 51, and tirucallane-type triterpenes 16-J.Further research on the chemical constituents of this species led us to the isolation of four novel biphenylneolignans 1-4. Herein, we describe their isolation and structural elucidation.
Mcb
dhle
1 and2
HO
RESULTSAND DISCUSSION
The methanol extract of the wood of E. longifoEia was fractionated by partitioning between methylene chloride and water. The methylene chloride fraction was purified by successive silica gel, medium pressure LC and high pressure LC to give four biphenylneolignans (l-4). Compounds 1 and 2, possessing the same molecular formulae, &H,,O,, were obtained as yellow needles. Their physical data were different from each other (I: mp 56-58”, [crlD + 1.3”; 2: mp W-62”, [crlr, - 2.5”), but they had similar spectroscopic properties. The ‘H NMR spectrum of 1 suggested the presence of two 1,2,4&substituted benzene rings, two methoxyl groups attached to the aromatic rings, a trans-olefin and four hydroxyl groups, two of which were primary, the others secondary. The 13CNMR spectrum of 1 also indicated the presence of these groups. Furthermore, three hydroxyl groups were revealed to be located successively from C-7’ to C-9’ and another primary one was an allylic alcohol by means of proton coupling sequences in the ‘H-‘H COSY spectrum. Another oxygen atom must be sited between the two aromatic rings because of the molecular formula and 13C chemical shifts at C-l and Cl’. These substituted aromatic ring systems were determined by the COLOC spectrum monitoring/ ‘H-13C *Author to whom correspondence should be addressed.
3: R=OMe 4. R=H
long range couplings and the presence of NOES between H-3 and OMe-2, and between H-3’ and OMe-2’. The NMR data of 2 were quite similar to those of 1. However, the chemical shifts of H-9’ and C-8’ were slightly different from one another. This difference was considered to be due to the different configuration at C-8’. Therefore, the structures of compounds I and 2 were elucidated to be 2,2’-dimethoxy+(3-hydroxyl-propenyl)-4’-(1,2,3-trihydroxypropyI)biphenyl ethers, which were stereoisomeric. Compounds 3 and 4 were obtained as yellow needles (mp 3: 68-70”, 4: 65-66”) and the molecular formulae C,,H,,O, (3) and CaoH,,O, (4) were determined by HRmass spectra. The ‘H NMR spectrum of 3 suggested the presence of two sets of four substituted benzene rings, one of which was symmetrical, three methoxyl groups and an allylic alcohol similar to 1 and 2. The 13C signals at 6 54.7 (d) and 64.1 (6) indicated the presence of an epoxide as a terminal moiety. A hydroxyl group was deduced to be substituted at C-7’ by the proton coupling sequence.
3993
3994
H. MORITAet al. Table
1. ‘HNMR
spectral
data of l-4
from Eurycoma
H
1
2
3 4 5
7.59 (d. J = 2.0)
7.59 (d. J = 1.7)
7.38 (dd, J = 8.0, 2.0)
7.42 (dd, J = 7.8, 1.7)
6 7 8 9 OMe-2 OMe-3 3’ 5’ 6 7 8’
7.24 6.85 6.55 4.56 3.74 -7.14 7.04 7.37 5.60 5.03
9’
4.41 (dd, J = 11.8, 3.8) 4.55 (dd, J = 11.8, 5.4) 3.72 (s) -
OMe-2’ OMe-6’
(d. J = 8.0) (d, J = 15.9) (dt, J = 15.9, 5.3) (d, J = 5.3) (s)
7.27 6.89 6.58 4.58 3.75
(d, J = 7.8) (d, J = 15.8) (dt, J = 15.8, 5.2) (d, J = 5.2) (s)
(d, J= 1.9) (dd, J = 8.3, 1.9) (d, J = 8.3) (d, J=5.1) (br ddd, J=4.9, 4.9, 4.9)
7.19 7.07 7.50 5.60 4.98
(d, J= 1.2) (dd, J = 8.3, 1.2) (d, J = 8.3) (d, J = 5.7) (br ddd, J=5.6, 5.6, 5.6)
3
4
7.15 (s)
7.14 (s) ._
7.33 6.91 6.57 4.59
7.32 6.91 6.57 4.59
(s) (d, J= 15.9) (dt, J= 15.9, 5.3) (d, J= 5.3)
3.58 7.32 7.22 1.22 6.08 3.97 6.2) 4.22 4.27 3.66 _-.
(s) (s) (s) (s) (d, J=6.7) (br ddd, J=6.2,
(s) (d, J = 15.9) (dt, J= 15.9, 5.3) (d. J= 5.3)
3.86 (s) 7.10 (s) 7.10 (s) 6.11 (d, J=7.0) 4.08 (br ddd, J=6.2,
4.11 (dd, J=11.8, 5.7) 4.40 (dd. J = 11.8, 3.6) 3.78 (s) __
The aromatic substitution pattern was determined by HMBC [7] correlations and the hydroxyl group was found to be at C-2. This structure was corroborated by the NOES between OMe-3 and H-4 and between OMe-2, OMe-6’ and H-3’, H-5’, and characterized the compound as 2-hydroxy-3,2’,6’-trimethoxy-4’-(2,3-epoxy-l-hydroxypropyl)-5-(3-hydroxyI-propenyl)biphenyl. Comparison of the rH NMR spectrum of 4 with that of 3 showed an aromatic proton in place of a methoxyl group with the disappearance of a symmetrical aromatic ring. The ‘H signals of H-3’, H-5’ and H-6’ characteristic of an ABXtype pattern were observed in methanol-d, (H-3’: 6 6.95, d, J = 1.9 Hz; H-5’: 6 6.82, dd, J = 1.9, 8.1 Hz; H-6’: 6 6.77, d, .I = 8.1 Hz). These results and HMBC correlations enabled the elucidation of the structure of 4 as 2-hydroxy-3,2’dimethoxy-4’-(2,3-epoxy-l-hydroxypropyl)-5-(3-hydroxyl-propenyl)biphenyl. A combination of 2-D NMR techniques, such as ‘H-‘H COSY, 13C-lH COSY, COLOC and HMBC spectra enabled us to make complete ‘H and 13C assignments of l-4 (Tables 1 and 2). The constituents of the families of the Magnoliales, especially the Magnoliaceae [8-121 and Lauraceae [13-181, are characterized by the presence of a series of unusual biphenylneolignans. However, this is the first isolation of biphenylneolignans from the Simaroubaceae.
longifolia (400 MHz, pyridine-d,)
4.26 4.31 3.73 3.73
Table
6.2, 6.2)
(dd, J = 10.8, 6.6) (dd, J= 10.8, 5.3) (s) (s)
(dd, J = 10.7, 6.7) (dd, J= 10.7, 5.5) (s)
2. 13CNMR spectral data of l-4 Eurycoma longifolia (100 MHz, pyridine-d,)
c 1 3 3 4 5 6 7 8 9 OMe-2 OMe-3 1’ 2’ 3’ 4’ 5’ 6’ 7’ 8’ 9 OMe-2 OMe-6’
6.2,
1
2
3
4
147.4 148.4 112.0 134.5 120.6 116.0 129.4 129.7 62.9 55.8
147.5 148.4 111.9 134.0 120.6 116.0 129.4 129.8 62.9 55.8
130.6 148.8 144.9 111.7 131.9 115.9 129.9 129.0 63.0
130.6 148.8 144.9 111.7 131.8 115.9 130.0 128.9 63.0 -
148.7 151.2 110.9 131.9 119.9 117.8 73.6 86.2 61.7 55.9 -
149.2 151.1 110.8 132.0 120.0 117.9 73.4 87.3 61.7 55.9
56.2 137.7 149.3 104.8 132.5 104.8 149.3 88.9 54.7 64.1 56.3 65.3
56.2 148.2 148.8 110.8 133.5 119.7 116.5 88.7 54.7 64.2 55.8
from
EXPERIMENTAL General. Mp: uncorr. ‘HNMR (400 MHz) and *sCNMR (100 MHz) were measured in pyiidine-d, and those of 4 also in methanol-d,, TMS as int. standard. Silica gel CC was carried out on Wakogel C-200 at amounts equivalent to 100 times those of the sample. Each final purification was done with MPLC and HPLC. Plant material. Wood of E. longifolia was collected in Indonesia in May 1990. Identification was made by Dr Kosasih Padmawinata, Natural Sciences, Bandung Institute of Technology, Indonesia. Extraction and isolation. Wood (4.5 kg) was crushed and extracted with hot MeOH. The coned extract was partitioned
between H,O and CH,Cl,. The CH,Cl,-sol. fr. was subjected to silica gel CC using CH,Cl,-MeOH stepwise elution. The fr. eluted with CH,Cl,-MeOH (3: 7) was purified by silica gelMPLC with n-hexane-EtOAc-MeOH (11: 9:2), ODS-MPLC with MeCN-Ha0 (11:29), then finally ODS-HPLC with MeCN-H,O (3 : 7 and 1: 3) to obtain compounds 1 (27 mg), 2 (25 mg), 3 (13 mg) and 4 (37 mg). Compound 1. Yellow needles, mp 56-58”. [n]u + 1.3” (MeOH; c 1.6). EI-MS m/z (rel. int.): 376 ([M] ‘, 10, calcd for C 20H 240 7: 376.1522, found: 376.1504). 206 (loo), 180 (62), 163 (21), 153 (32), 137 (73), 124 (51). 91 (39), 78 (25). 65 (34). UV 22:” (1OgE): 228
Biphenyls
from Eurycoma
(4.40), 259 (4.36), 267 (4.33). IR $$ cm- i: 3450,1520, 1270, 1130, 1030, 860. Compound 2. Yellow needles, mp 60-62”. [alo -2.5” (MeOH; c 1.6). EI-MS m/z (rel. int.): 376 ([Ml’, 8, calcd for C2,,Hz407: 376.1522, found: 376.1507), 358 (4), 206 (27), 180(63), 152 (42), 137 (lOO), 124 (52), 91(98), 78 (51), 65 (SO). UV 2::” (logs): 208 (4.20), 265 (3.92). IR vfi; cm-‘: 3450, 1510, 1270, 1130, 1030,860. Compound 3. Yellow needles, mp 68-70”. [a]n - 2.6” (MeOH; c 0.8). EI-MS m/z (rel. int.): 388 ([Ml +, 100, calcd for C,, H,,O,: 388.1522, found: 388.1558) 370 (96), 356 (32), 339 (32), 222 (64), E’oH (log E): 211 (4.48) 274 (4.04). 167 (76), 115 (36), 92 (60). UV &,,.. IR vz’ cm-‘: 3450. Compound 4. Yellow needles, mp 65-66”. [alo - 9.7” (MeOH; ~0.7). EI-MS m/z (rel. int.): 358 ([Ml’, 82, calcd for C 20H 220 6: 358.1416, found: 358.1744), 340 (lOO), 137 (57), 115 (21), 91 (27). UV 1::” (logs): 222 (4.42) 277 (4.29). IR v=; cm-‘: 3450. ‘HNMR (CD,OD) 6: 6.94 (br s, H-4), 6.96 (br s, H-6), 6.53 (d, J =15.8Hz,H-7),6.22(dt,5=15.8,5.9Hz,H-8),4.19(dd,5=1.3, 5.8 Hz, H-9), 3.86 (s, OMe-3), 6.95 (d, .I= 1.9 Hz, H-3’), 6.82 (dd, J =1.9, 8.1 Hz, H-S), 6.77 (d, 5=8.1 Hz, H-6’), 5.52(d, J=6.3 Hz, H-7’), 3.49 (br ddd, J=6.4, 6.4, 6.4 Hz, H-8’), 3.79 (m, H-9’), 3.85 (m, H-9’), 3.80 (s, OMe-2’). “CNMR (CD,OD) 6: 130.4 (C-l), 149.1 (C-2), 145.5 (C-3), 112.2 (C-4), 132.6 (C-5), 116.2 (C-6), 132.0 (C-7), 127.6 (C-8), 63.9 (C-9), 56.8 (OMe-3), 147.6 (C-l’), 149.3 (C2’), 110.6 (C-3’). 134.5 (C-4’) 119.8 (C-S), 116.5 (C-6’), 89.3 (C-7’) 55.1 (C-8’) 64.9 (C-9’), 56.4 (OMe-2’). REFERENCES
1. Cassady, J. M. and Suffness, M. (1980) in Arqicancer Agents Based ORNatural Product Models, p. 254. Academic Press, New York.
longifolia
3995
2. Chan, K. L., G’Neill, M. J., Phillipson, J. D. and Warhurst, D. C. (1986) PIanta Med. 105. 3. Morita, H., Kishi, E., Takeya, K., Itokawa, H. and Tanaka, 0. (1990) Chem. Letters 749. 4. Itokawa, H., Kishi, E., Morita, H., Takeya, K. and Iitaka, Y. (1991) Tetrahedron Letters 32, 1803. 5. Itokawa, H., Kishi, E., Morita, H., Takeya, K. and Iitaka, Y. (1991) Chem. Letters 2221. Itokawa, H., Kishi, E., Morita, H. and Takeya, K. (1992) Chem. Pharm. Bull. 40, 1053. Bax, A. and Summers, M. F. (1986) J. Am. Chem. Sot. 108, 2094. Sugii, Y. (1930) Yakugaku Zasshi 50, 183. Fujita, M., Itokawa, H. and Sashida, Y. (1972) Chem. Pharm. Bull. 20, 212. 10. Fujita, M., Itokawa, H. and Sashida, Y. (1973) Yakugaku Zasshi 93. 422. 11. El-Feraly, F. S. and Li, W.-S. (1978) Lloydia 41,442. 12. Ito, K., Iida, T., Ichino, K., Tsunezuka, M., Hattori, M. and Namba, T. (1982) Chem. Pharm. Bull. 30, 3347. 13. Holloway, D. M. and Scheinmann, F. (1973) Phytochemistry 12, 1503. 14. De Diaz, A. M. P., Gottlieb, H. E. and Gottlieb, 0. R. (1980) Phytochemistry 19, 681. 15. El-Feraly, F. S., Cheathum, S. F. and Breedlove, R. L. (1983) Lloydia 46, 493. 16. Suarez, M., Bonilla, J., De Diaz, A. M. P. and Achenbach, H. (1983) Phytochemistry 22,609. 17. Chen, F.-C., Lee, J.-S. and Lin, Y.-M. (1983) Phytochemistry 22, 616. 18. El-Feraly, F. S. (1984) Phytochemistry 23, 2329.