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Sesquiterpenoids from Dysoxylum schiffneri
Ph, rochrmrir~~~. Vol. 47. No. 7. pp. 1421 ,422. ,998 ( 19YX Elsrvw Saence Ltd. All nghtr reserved Prmtcd ,n Great Brilam 00319422.98 s19.00+0.00
Pergamon PII: SOO31-9422(97)00705-X
SESQUITERPENOIDS
FROM
DULCIE A. MULHOLLAND,* Natural
Products
Research
Key Word xycalamenene;
Group.
Department
DYSOXYLUM
SCHIFFNERI
SERGE IOURINE and DAVID A. H. TAYLOR of Chemistry,
Index-D~so.~$um schifjkeri; schiffnerone A; schiffnerone B.
University
Meliaceae;
of Natal,
Durban
sesquiterpenoids;
4041, South Africa
(+)-S-hydro-
(Meliaceae) has yielded the known (+)-S-hydroxycalamenene, Abstract-The wood of D~w.~yhtm sch@neri the novel sesquiterpenoid, schiffnerone A (I ,5-dihydroxy- I ,3,5_bisabolatrienI O-one) and the novel trisnorsesquiterpenoid, schiffnerone B (2-hydroxy- 1I, 12,13-trinor-7-calamenone). 0 1998 Elsevier Science Ltd. All rights reserved
INTRODUCTION
member of the D~.so.~~/urn sch(f;r)leri is an Australian Meliaceae family. The genus Dysoxylum is noted for the range of classes of compounds produced including diterpenoids, sesquiterpenoids, alkaloids, limonoids and other triterpenoids. The hexane, chloroform and methanol extracts of D. .sch[fj?neri were examined. All three extracts yielded (+)-S-hydroxycalamenene (1) which has been isolated previously from Dwo.~~lutn wutungulum [I]. This compound has been shown to exhibit fish toxicity against Or~~zius lutipes at 5 ppm concentration and to have moderate anti-bacterial activity against Gram-positive bacteria at 5-20 ppm. The chloroform extract also yielded the novel sesschiffnerone A (2) and the trisquiterpenoid, norsesquiterpenoid, schiffnerone B (3). RESULTS AND DISCUSSION
(+)-8-Hydroxycalamenene (1) was identified by comparison of NMR, mass spectral and optical rotation data with literature values. High resolution mass spectroscopy of schiffnerone A (2), indicated a molecular formula of CliHZZ03. A peak at m/z 207 indicated the loss of an isopropyl group. The IR spectrum showed a broad band at 3440 cm-’ (OH stretching) and a band at 1705 cm-’ (C=O stretching). A singlet at 6 6.18 (2H) was assigned to two equivalent protons in a symmetrically-substituted benzene ring. A broad singlet at 6 5.31 (2H) disappeared on addition of DZO, indicating two equivalent hydroxy groups on
*Author to whom correspondence
should be addressed.
the benzene ring instead of only one as in compound I. Coupling was noted between the aromatic proton signal at S 6.18 and a three proton singlet at (r 2.16. From this it was deduced that a 2,6-dihydroxy-4methylbenzene ring was present in the molecule. A six proton doublet at 6 1.01 was seen to be coupled to a multiplet integrating to 1H at 6 2.55. This resonance was not further coupled, thus the keto group was placed here giving a partial structure of (CH,),CHCO. A three proton doublet at 6 1.32 was coupled to a multiplet at 6 3.19 (IH). This resonance was coupled to two multiplets at 6 1.70(I H) and 6 2.26 (1 H). These two multiplets were further coupled to a multiplet at 6 2.41 (2H) which was not further coupled. This indicated the partial structure CH,.CH.CH2.CH2. Assembling the partial structures gave compound 2. Schiffnerone B was isolated in very small amounts. The mass spectrum indicated a molecular formula of C,zH,40, indicating that the molecule had lost three carbon atoms. The IR spectrum also showed OH and C=O stretching (3418 and 1654 cm-‘, respectively). The ‘H NMR spectrum contained resonances ascribable to two aromatic protons (6 6.77 and 7.43). These were both coupled to a three proton methyl group singlet at 6 2.29. A sharp singlet at fi 4.87 (1H) disappeared on addition of D,O indicating a hydroxy group. This was placed at C-S as in 1 and 2. A methyl proton doublet at S 1.31 (H1-14) was coupled to a multiplet at 6 3.32 (H-l) which was further coupled to a multiplet at 6 2.25 (H-2a). Coupling was observed between this multiplet at 6 2.25 and three one proton multiplets at 6 I .99 (H-2b), 2.55 (H-3a) and 2.80 (H3b). No resonances ascribable to an isopropyl group were present indicating that this group had been lost. The keto group indicated in the IR spectrum was 1421
1422
0
1
placed at C-4. Thus structure 3 is proposed for schiffnerone B. The “C NMR spectrum was unfortunately too weak to confirm the presence of the keto group.
Table 2. “C’ NMR data for compounds
I 3
EXPERIMENTAL .sch~f~kv?
was
collected and identified in Australia by Prof D. A. H. Taylor and Dr Tony Irvine. Voucher specimens are retained in the Forest Herbarium. Oxford (DAHT 329). Dried, milled wood (200 g) was extracted SLICcessively with hexane, CHCI, and MeOH. The extracts were separated using CC over silica gel (Merck 93X5) using MeC&/EtOAc in varying proportions. All three extracts yielded X-hydroxycalamenene (I). Compounds 2 and 3 were isolated from the CHCI, extract. NMR spectra were recorded on a Varian Gemini 300 NMR spectrometer and NMR data is given in Tables 1 and 2. 8-H~~~o_~~c~u/u111zp11o1(’ (1). I ,2,3,4-tetrahydro-4-isopropyl- I ,6_dimethylnaphthalene, (2.9 g), H RMS 777;:
Table
I. ‘H NMR
data for compounds
l-3
(300 MHz.
CDCI,)
H-l H-2 % H-3 a b H-4 H-5 H-7 H-l I H-12 H-13 H-14 3H-I5 8-OH IO-OH
1
2
3
3.07 111
3.19 111
3.32 111
1.81 1.51 171 111
I .70 W 2.26 n?
’ 35 11, _.-_ I .99 111
I .78 111
2.41 ,?I
2.55 11, 2.80 111
hs
6.18 hs
hs
6.18 hs
7.43 h\ 6.77 II.\
2.46 6.57 6.39 I .98 0.81 0.97
177
&I d(7.0) r/ (7.0) 1.20d (7.0) 2.21 s 5.30 hs --
2.55 171
I .Ol t/(7.0) 1.01 d(7.0)
1.32t/(7.0) 2.16 s 5.31 h.c 5.3 I 11s
I.31 r/(6.8) 2.29 .\ 4.87 IL\
l-3 (75 MHz. CDCI,)
2
2
D~w.\-?hu~7
3.
2.
4 s 6 7 8 9 10
II 12 I3 14 15
26.8 27.3 19.3 43.3 123.1 135.1 113.6 153.1 126.4 141.3 33.4 19.8 21.2 22.3 21.4
rl t
I tl rl .F tl s s s cl yil/iq q
29.0d 29.2 f 38.5 / 217.5 s 155.2 s 115.l.v 109.8 (I 155.2 s 137.3 s 109.x .Y 40. I d 18.3 qi 18.1 yt 19.1 q 20.9 q
3 26.1 d 29.1 t 33.x I *
I20.1tit * 121.0 (f.I 151.1 .s * *
14.0 q 18.4 q
* Sample too weak for detection of these resonances. t Value\ in the same column may be interchanged.
218.1652 (C,5H,,0 req. 218.1670), [xl;; = +36.5’(c, 0.050 in CHCI,) (lit. +3X [I]). Sd7iffi7cmw A (2). I .5-dihydroxy-I ,3,5-bisabolatrien-IO-one (47 mg), mp 128-130 , [cx];’= +80”’ (CHCI,: (’0.060). HRMS m/I 250.1579 (C,2H210~ req. 250.1659). IR: ;E$’ cm-‘: 3439, 2968, 2926, 2877, 3705, 1618, 1467, 1425, 1361, 1263. UV LcF nm: 228 (< = 13925), 264 (< = 7485) Sd7iffircw77r B (3). 2-hydroxy-I I, 12, I3-trinor-7-calamenonc (2.9 mg). HRMS m/z 190.1066 (C,?H,,O? requires 190.0994). IR $::y’ cm-.‘: 3418, 2930, 2895. 2098 3 I653 >1579 3 1470. uv i”““. m.ir 229 (t = 8527) 265 (< = 5284). 3 I5 (5 = 1855) Ac,l\tto,~,/l,~~~!ypn?mt.r-We are extremely grateful to Dr Tony Irvine for assistance in collection and identification of plant material. We thank Professor Joe Connolly for his helpful discussions regarding these compounds. S.I. thanks the Foundation for Research and Development and the SA Council of Jewry for bursaries. This research was funded by the University of Natal Research Fund. REFERENCES
I. Nishizawa. M.. Inoue, A., Sastrapradja. S. and Hayashi, V., P/l?,toc/lr,mist~~, 1983, 22. 2083.
Pergamon PII: SOO31-9422(97)00705-X
SESQUITERPENOIDS
FROM
DULCIE A. MULHOLLAND,* Natural
Products
Research
Key Word xycalamenene;
Group.
Department
DYSOXYLUM
SCHIFFNERI
SERGE IOURINE and DAVID A. H. TAYLOR of Chemistry,
Index-D~so.~$um schifjkeri; schiffnerone A; schiffnerone B.
University
Meliaceae;
of Natal,
Durban
sesquiterpenoids;
4041, South Africa
(+)-S-hydro-
(Meliaceae) has yielded the known (+)-S-hydroxycalamenene, Abstract-The wood of D~w.~yhtm sch@neri the novel sesquiterpenoid, schiffnerone A (I ,5-dihydroxy- I ,3,5_bisabolatrienI O-one) and the novel trisnorsesquiterpenoid, schiffnerone B (2-hydroxy- 1I, 12,13-trinor-7-calamenone). 0 1998 Elsevier Science Ltd. All rights reserved
INTRODUCTION
member of the D~.so.~~/urn sch(f;r)leri is an Australian Meliaceae family. The genus Dysoxylum is noted for the range of classes of compounds produced including diterpenoids, sesquiterpenoids, alkaloids, limonoids and other triterpenoids. The hexane, chloroform and methanol extracts of D. .sch[fj?neri were examined. All three extracts yielded (+)-S-hydroxycalamenene (1) which has been isolated previously from Dwo.~~lutn wutungulum [I]. This compound has been shown to exhibit fish toxicity against Or~~zius lutipes at 5 ppm concentration and to have moderate anti-bacterial activity against Gram-positive bacteria at 5-20 ppm. The chloroform extract also yielded the novel sesschiffnerone A (2) and the trisquiterpenoid, norsesquiterpenoid, schiffnerone B (3). RESULTS AND DISCUSSION
(+)-8-Hydroxycalamenene (1) was identified by comparison of NMR, mass spectral and optical rotation data with literature values. High resolution mass spectroscopy of schiffnerone A (2), indicated a molecular formula of CliHZZ03. A peak at m/z 207 indicated the loss of an isopropyl group. The IR spectrum showed a broad band at 3440 cm-’ (OH stretching) and a band at 1705 cm-’ (C=O stretching). A singlet at 6 6.18 (2H) was assigned to two equivalent protons in a symmetrically-substituted benzene ring. A broad singlet at 6 5.31 (2H) disappeared on addition of DZO, indicating two equivalent hydroxy groups on
*Author to whom correspondence
should be addressed.
the benzene ring instead of only one as in compound I. Coupling was noted between the aromatic proton signal at S 6.18 and a three proton singlet at (r 2.16. From this it was deduced that a 2,6-dihydroxy-4methylbenzene ring was present in the molecule. A six proton doublet at 6 1.01 was seen to be coupled to a multiplet integrating to 1H at 6 2.55. This resonance was not further coupled, thus the keto group was placed here giving a partial structure of (CH,),CHCO. A three proton doublet at 6 1.32 was coupled to a multiplet at 6 3.19 (IH). This resonance was coupled to two multiplets at 6 1.70(I H) and 6 2.26 (1 H). These two multiplets were further coupled to a multiplet at 6 2.41 (2H) which was not further coupled. This indicated the partial structure CH,.CH.CH2.CH2. Assembling the partial structures gave compound 2. Schiffnerone B was isolated in very small amounts. The mass spectrum indicated a molecular formula of C,zH,40, indicating that the molecule had lost three carbon atoms. The IR spectrum also showed OH and C=O stretching (3418 and 1654 cm-‘, respectively). The ‘H NMR spectrum contained resonances ascribable to two aromatic protons (6 6.77 and 7.43). These were both coupled to a three proton methyl group singlet at 6 2.29. A sharp singlet at fi 4.87 (1H) disappeared on addition of D,O indicating a hydroxy group. This was placed at C-S as in 1 and 2. A methyl proton doublet at S 1.31 (H1-14) was coupled to a multiplet at 6 3.32 (H-l) which was further coupled to a multiplet at 6 2.25 (H-2a). Coupling was observed between this multiplet at 6 2.25 and three one proton multiplets at 6 I .99 (H-2b), 2.55 (H-3a) and 2.80 (H3b). No resonances ascribable to an isopropyl group were present indicating that this group had been lost. The keto group indicated in the IR spectrum was 1421
1422
0
1
placed at C-4. Thus structure 3 is proposed for schiffnerone B. The “C NMR spectrum was unfortunately too weak to confirm the presence of the keto group.
Table 2. “C’ NMR data for compounds
I 3
EXPERIMENTAL .sch~f~kv?
was
collected and identified in Australia by Prof D. A. H. Taylor and Dr Tony Irvine. Voucher specimens are retained in the Forest Herbarium. Oxford (DAHT 329). Dried, milled wood (200 g) was extracted SLICcessively with hexane, CHCI, and MeOH. The extracts were separated using CC over silica gel (Merck 93X5) using MeC&/EtOAc in varying proportions. All three extracts yielded X-hydroxycalamenene (I). Compounds 2 and 3 were isolated from the CHCI, extract. NMR spectra were recorded on a Varian Gemini 300 NMR spectrometer and NMR data is given in Tables 1 and 2. 8-H~~~o_~~c~u/u111zp11o1(’ (1). I ,2,3,4-tetrahydro-4-isopropyl- I ,6_dimethylnaphthalene, (2.9 g), H RMS 777;:
Table
I. ‘H NMR
data for compounds
l-3
(300 MHz.
CDCI,)
H-l H-2 % H-3 a b H-4 H-5 H-7 H-l I H-12 H-13 H-14 3H-I5 8-OH IO-OH
1
2
3
3.07 111
3.19 111
3.32 111
1.81 1.51 171 111
I .70 W 2.26 n?
’ 35 11, _.-_ I .99 111
I .78 111
2.41 ,?I
2.55 11, 2.80 111
hs
6.18 hs
hs
6.18 hs
7.43 h\ 6.77 II.\
2.46 6.57 6.39 I .98 0.81 0.97
177
&I d(7.0) r/ (7.0) 1.20d (7.0) 2.21 s 5.30 hs --
2.55 171
I .Ol t/(7.0) 1.01 d(7.0)
1.32t/(7.0) 2.16 s 5.31 h.c 5.3 I 11s
I.31 r/(6.8) 2.29 .\ 4.87 IL\
l-3 (75 MHz. CDCI,)
2
2
D~w.\-?hu~7
3.
2.
4 s 6 7 8 9 10
II 12 I3 14 15
26.8 27.3 19.3 43.3 123.1 135.1 113.6 153.1 126.4 141.3 33.4 19.8 21.2 22.3 21.4
rl t
I tl rl .F tl s s s cl yil/iq q
29.0d 29.2 f 38.5 / 217.5 s 155.2 s 115.l.v 109.8 (I 155.2 s 137.3 s 109.x .Y 40. I d 18.3 qi 18.1 yt 19.1 q 20.9 q
3 26.1 d 29.1 t 33.x I *
I20.1tit * 121.0 (f.I 151.1 .s * *
14.0 q 18.4 q
* Sample too weak for detection of these resonances. t Value\ in the same column may be interchanged.
218.1652 (C,5H,,0 req. 218.1670), [xl;; = +36.5’(c, 0.050 in CHCI,) (lit. +3X [I]). Sd7iffi7cmw A (2). I .5-dihydroxy-I ,3,5-bisabolatrien-IO-one (47 mg), mp 128-130 , [cx];’= +80”’ (CHCI,: (’0.060). HRMS m/I 250.1579 (C,2H210~ req. 250.1659). IR: ;E$’ cm-‘: 3439, 2968, 2926, 2877, 3705, 1618, 1467, 1425, 1361, 1263. UV LcF nm: 228 (< = 13925), 264 (< = 7485) Sd7iffircw77r B (3). 2-hydroxy-I I, 12, I3-trinor-7-calamenonc (2.9 mg). HRMS m/z 190.1066 (C,?H,,O? requires 190.0994). IR $::y’ cm-.‘: 3418, 2930, 2895. 2098 3 I653 >1579 3 1470. uv i”““. m.ir 229 (t = 8527) 265 (< = 5284). 3 I5 (5 = 1855) Ac,l\tto,~,/l,~~~!ypn?mt.r-We are extremely grateful to Dr Tony Irvine for assistance in collection and identification of plant material. We thank Professor Joe Connolly for his helpful discussions regarding these compounds. S.I. thanks the Foundation for Research and Development and the SA Council of Jewry for bursaries. This research was funded by the University of Natal Research Fund. REFERENCES
I. Nishizawa. M.. Inoue, A., Sastrapradja. S. and Hayashi, V., P/l?,toc/lr,mist~~, 1983, 22. 2083.