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Anthraquinones from Knoxia valerianoides
Znu ZnoU et al.
766
0
1:
OH
5: R,=CH,,
R= CH,OCH,CH,
R,=OH
R,=CHO.
2: R-CHO
9: R,=H,
3: R=CH,OH
7: R, = H, 4 = CH,OCH,CH,.
4: RICH,
8: R,=H,
R,=CHO,
R,=OH,
9: R, =CH,,
Table
1. ‘HNMR
R,=OH R, = OH
R,=CH,
R,=CH,OH.
\=OH
data of l-9* Compound
Proton
I
I-OH I-OMe 2-OH 2-CHO
13.52 -..
2-CH, 2-Me
4.47 .._
3-OH 3-Me 4-H S-H+ S-OH 6-H: 6-OMe 7-HS(j 8-H+(j OCHJ MelI
10.48
2 14.17
3 13.39
4 13.48 ._
5
6 14.10
7 13.25
II
9
13.14
3.97
3.88 11.30
10.37 --
10.37
10.50
4.52 2.1 I 11.38 7.29
Il.27
7.31
10.40 7.24
12.70
12.45
12.71
12.77
3.95 7.44 7.79 3.49 1.10
3.97 1.49 7.77 -
3.95 7.45 7.77
3.95 1.44 7.87
7.3 I
._ 4.48
12.12
12.68
4.56
11.48
11.20
7.49 8.65-8.85
7.40 8.30
7.29 8.19
2.09 7.30 8.17-8.22
7.90
7.80
7.9 I
7.92
7.89
7.80 8 30
7.91 8.19 3.50
7.92 8.17-8.22
7.89 8.14-8.17
_
1.10
7.90 8.65-
8.85
7.52 8.14.-8.17
*Compounds 1-5 and 7-9 were recorded in DMSO-d,, and 6 was recorded in CDCI,. chemical shift values are reported as d values (ppm) from TMS at 400 MHz unless indicated in +$I, the signals are singlets. t:For 5-9, the H-5 and H-8, and H-6 and H-7 signals overlapped, respectively. $For 1-4, H-7 and H-8 are doublets, with J = 8 Hz for I, 8.4 Hz for 2. 8.5 Hz for 3 and 8.6 Hz for 4, respectively. 11 For the OCH,Me group, the CH, signal is a quartet with J = 7.0 Hz, and the Me signal is a triplet with J = 7.0 Hz.
supported that this proton was located on the opposite side to H-8, i.e. the C-4 position of the other ring. Irradiation of this proton also enhanced C-2 and C-l 1, irradiation of the hydroxyl signal at 613.52 enhanced C-l, C-2 and C-11, and irradiation of the aromatic methylene signal (64.47) enhanced C-l, C-2, C-3 and the carbon signal of the methylene of the ethoxyl group. The latter group was also enhanced by the irradiation of the methyl signal of the ethoxyl group. Thus, the ethoxymethyl function should be at the C-2 position, and the two phenolic groups should be at the C-l and C-3 positions; even though no enhancements were observed when the C-3-OH at 6 11.48 was irradiated with J = 8, 6 and 4 Hz. These conclusions are consistent with those from ‘H, ROESY, NOE difference and HMQC spectra. Therefore, this compound should be 2ethoxymethyL6-
methoxy-1,3,5-trihydroxy-9,1O_anthraquinone, which we have named 2-ethoxymethylknoxiavaledin. The two remaining signals at 6 163.5 and 133.6 could be assigned to the hydroxylated aromatic carbons C-3 and C-12, an aromatic carbon, respectively, thereby completing the unambiguous assignments. Comparison with the data of 4 and another similar compound, ibericin (7), which has the same substitution ring as 1, showed that the corresponding ‘H NMR data are very close (Table 1). Ibericin was considered to be an artifact, arising from its parent compound during the extraction of the plant with ethanol [3,4]. Similarly, I may arise from 2-hydroxymethylknoxiavaledin (3) during the course of extraction and separation with a trace of ethanol in the chloroform, ethyl acetate and methanol solvents, which were used in these treatments.
768
ZHU
THOU
National Cancer Institute, Bethesda, MD, U.S.A. We thank Dr X.-F. Wang for identification of the plant, Dr R. R. Gil for on-line structure searching in the STN International database. Mr R. Dvorak and Dr B.-L. Liu for mass spectra, Dr G. Doss (formerly A. N. AbdelSayed) for the original establishment of the selective INEPT pulse program on the NMC-360 spectrometer at UIC [12], and the Research Resources Center, University of Illinois at Chicago for the provision of NMR spectroscopic facilities.
er a/.
Stikhin, V. A., Bank’kovskii, A. I. and Perel’son, M. E. (1966) Khim. Prirodn. Soedin. 2, 12. Venkateshwar Rao. G. and Rao, P. S. (1983) J. Ind. Chem. Sot. 60, 585.
Burnett,
A. R. and Thomson,
chemistry
R. H. (1968) Phyto-
7, 1421.
Bothner-By, A. A., Stephens, R. L., Lee, J., Warren, C. D. and Jeanloz, R. W. (1984) J. Am. Chem. Sot. 106, 811.
7. Summers,
M. F., Marzilli,
L. G. and Bax, A. (1986)
J. Am. Chem. Sot. 108, 4285.
REFEREKCES 1.
Wang, X.-F., Chen, J.-Y., Wen, T. and Lu, J.-L. (1985) Acta Pharmac.
Sin. 20, 615.
in Naturally Occurring Quinones (Thomson, R. H., ed.), 2nd Edn, pp. 376, 382. Scientific Press, London.
2. (1971)
8. Griesinger, C. and Ernst, R. R. (1987) J. Map. Reson. 75, 261. 9. Bax, A. (1984) J. Magn. Reson. 57, 3 14. 10. Cordell, G. A. (1991) Phytochem. Anulyt. 2, 49. 1I. Cordell, G. A. and Kinghorn, A. D. (1991) Tetrahedron 47, 3521.
12. Abdel-Sayed, Letters
A. N. and Bauer, L. (1986) Tetrahedron
27, 1003.
766
0
1:
OH
5: R,=CH,,
R= CH,OCH,CH,
R,=OH
R,=CHO.
2: R-CHO
9: R,=H,
3: R=CH,OH
7: R, = H, 4 = CH,OCH,CH,.
4: RICH,
8: R,=H,
R,=CHO,
R,=OH,
9: R, =CH,,
Table
1. ‘HNMR
R,=OH R, = OH
R,=CH,
R,=CH,OH.
\=OH
data of l-9* Compound
Proton
I
I-OH I-OMe 2-OH 2-CHO
13.52 -..
2-CH, 2-Me
4.47 .._
3-OH 3-Me 4-H S-H+ S-OH 6-H: 6-OMe 7-HS(j 8-H+(j OCHJ MelI
10.48
2 14.17
3 13.39
4 13.48 ._
5
6 14.10
7 13.25
II
9
13.14
3.97
3.88 11.30
10.37 --
10.37
10.50
4.52 2.1 I 11.38 7.29
Il.27
7.31
10.40 7.24
12.70
12.45
12.71
12.77
3.95 7.44 7.79 3.49 1.10
3.97 1.49 7.77 -
3.95 7.45 7.77
3.95 1.44 7.87
7.3 I
._ 4.48
12.12
12.68
4.56
11.48
11.20
7.49 8.65-8.85
7.40 8.30
7.29 8.19
2.09 7.30 8.17-8.22
7.90
7.80
7.9 I
7.92
7.89
7.80 8 30
7.91 8.19 3.50
7.92 8.17-8.22
7.89 8.14-8.17
_
1.10
7.90 8.65-
8.85
7.52 8.14.-8.17
*Compounds 1-5 and 7-9 were recorded in DMSO-d,, and 6 was recorded in CDCI,. chemical shift values are reported as d values (ppm) from TMS at 400 MHz unless indicated in +$I, the signals are singlets. t:For 5-9, the H-5 and H-8, and H-6 and H-7 signals overlapped, respectively. $For 1-4, H-7 and H-8 are doublets, with J = 8 Hz for I, 8.4 Hz for 2. 8.5 Hz for 3 and 8.6 Hz for 4, respectively. 11 For the OCH,Me group, the CH, signal is a quartet with J = 7.0 Hz, and the Me signal is a triplet with J = 7.0 Hz.
supported that this proton was located on the opposite side to H-8, i.e. the C-4 position of the other ring. Irradiation of this proton also enhanced C-2 and C-l 1, irradiation of the hydroxyl signal at 613.52 enhanced C-l, C-2 and C-11, and irradiation of the aromatic methylene signal (64.47) enhanced C-l, C-2, C-3 and the carbon signal of the methylene of the ethoxyl group. The latter group was also enhanced by the irradiation of the methyl signal of the ethoxyl group. Thus, the ethoxymethyl function should be at the C-2 position, and the two phenolic groups should be at the C-l and C-3 positions; even though no enhancements were observed when the C-3-OH at 6 11.48 was irradiated with J = 8, 6 and 4 Hz. These conclusions are consistent with those from ‘H, ROESY, NOE difference and HMQC spectra. Therefore, this compound should be 2ethoxymethyL6-
methoxy-1,3,5-trihydroxy-9,1O_anthraquinone, which we have named 2-ethoxymethylknoxiavaledin. The two remaining signals at 6 163.5 and 133.6 could be assigned to the hydroxylated aromatic carbons C-3 and C-12, an aromatic carbon, respectively, thereby completing the unambiguous assignments. Comparison with the data of 4 and another similar compound, ibericin (7), which has the same substitution ring as 1, showed that the corresponding ‘H NMR data are very close (Table 1). Ibericin was considered to be an artifact, arising from its parent compound during the extraction of the plant with ethanol [3,4]. Similarly, I may arise from 2-hydroxymethylknoxiavaledin (3) during the course of extraction and separation with a trace of ethanol in the chloroform, ethyl acetate and methanol solvents, which were used in these treatments.
768
ZHU
THOU
National Cancer Institute, Bethesda, MD, U.S.A. We thank Dr X.-F. Wang for identification of the plant, Dr R. R. Gil for on-line structure searching in the STN International database. Mr R. Dvorak and Dr B.-L. Liu for mass spectra, Dr G. Doss (formerly A. N. AbdelSayed) for the original establishment of the selective INEPT pulse program on the NMC-360 spectrometer at UIC [12], and the Research Resources Center, University of Illinois at Chicago for the provision of NMR spectroscopic facilities.
er a/.
Stikhin, V. A., Bank’kovskii, A. I. and Perel’son, M. E. (1966) Khim. Prirodn. Soedin. 2, 12. Venkateshwar Rao. G. and Rao, P. S. (1983) J. Ind. Chem. Sot. 60, 585.
Burnett,
A. R. and Thomson,
chemistry
R. H. (1968) Phyto-
7, 1421.
Bothner-By, A. A., Stephens, R. L., Lee, J., Warren, C. D. and Jeanloz, R. W. (1984) J. Am. Chem. Sot. 106, 811.
7. Summers,
M. F., Marzilli,
L. G. and Bax, A. (1986)
J. Am. Chem. Sot. 108, 4285.
REFEREKCES 1.
Wang, X.-F., Chen, J.-Y., Wen, T. and Lu, J.-L. (1985) Acta Pharmac.
Sin. 20, 615.
in Naturally Occurring Quinones (Thomson, R. H., ed.), 2nd Edn, pp. 376, 382. Scientific Press, London.
2. (1971)
8. Griesinger, C. and Ernst, R. R. (1987) J. Map. Reson. 75, 261. 9. Bax, A. (1984) J. Magn. Reson. 57, 3 14. 10. Cordell, G. A. (1991) Phytochem. Anulyt. 2, 49. 1I. Cordell, G. A. and Kinghorn, A. D. (1991) Tetrahedron 47, 3521.
12. Abdel-Sayed, Letters
A. N. and Bauer, L. (1986) Tetrahedron
27, 1003.