CN101265212B - Antineoplastic alkanna tinctoria ketoximes derivatives - Google Patents
Antineoplastic alkanna tinctoria ketoximes derivatives Download PDFInfo
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Abstract
The invention discloses lithospermum ketoxime derivant which can be used for resisting tumour in the technology field of medicine. The lithospermum ketoxime derivant is 5, 8-dimethoxy-1, 4-naphthoquinone derivant which is replaced by 6-, and has the following structural formula, wherein, R is alkyl and aralkyl. The lithospermum ketoxime derivant is synthesized, and the antitumor activity thereof is measured; alkannin is structurally modified and reorganized, so that an antitumor compound with lowered toxicity and increased water-solubility is obtained.
Description
Technical field
The present invention relates to the derivative of class medicine technical field, specifically is that a class can be used for antineoplastic Asian puccoon ketoximes derivatives.
Background technology
Many antitumor drugs of using clinically all are natural products or derive from natural product at present, as camptothecine, vinealeucoblastine(VLB), vincristine(VCR) etc.The Shikonin compounds is the class natural product that occurring in nature extensively exists, have and studies show that much this compounds has notable antitumor activity, be applied to clinically but also there is not this compounds to be used as antitumor drug up to now, this mainly is because the toxicity of this compounds and water-soluble relatively poor and limited their application.The toxicity of Shikonin may derive from two aspects: (1) naphthoquinones is left away by pendant hydroxyl group and the alkylating that produces causes cytotoxicity widely.(2) complexing action of naphthazarin structure and metal ion, the toxic side effect that causes the ion imbalance of organism to cause.Therefore if can adopt appropriate means to improve its toxicity and increase water-solublely, will lay a good foundation for the Shikonin series antineoplastic medicament that successful exploitation can be used clinically.The polarity of oxime is stronger, introduces the wetting ability that the strong group of polarity will improve compound greatly in compound.
Find by prior art documents, it mainly is the modification that hydroxy esterification on its side chain is carried out that the Shikonin compounds is carried out structure of modification, as: Chinese patent, publication number: CN1420111, title: naphthalene alizarin derivatives and its production and use, Chinese patent and for example, publication number: CN1112363, title: preparation 5, the method of 8-dihydronaphthalene quinone derivative, new 5,8-dihydronaphthalene quinone derivative and they are as the purposes of anticarcinogen, and these two technology are not put down in writing pendant hydroxyl group is oxidized to carbonyl is introduced oxime then in the Shikonin structure content.
Summary of the invention
The present invention is directed to the deficiency that prior art exists, provide a class to can be used for antineoplastic Asian puccoon ketoximes derivatives, and measured its anti-tumor activity,, obtain toxicity and reduce and water-soluble enhanced antineoplastic compound by Shikonin is carried out structural modification and transformation.
The present invention is achieved by the following technical solutions, describedly can be used for antineoplastic Asian puccoon ketoximes derivatives, promptly 6-replace 5,8-dimethoxy-1, the 4-naphthoquinone derivatives has following general structure:
R is an alkyl, aralkyl.
More specifically, R is a hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, n-pentyl, 3-methyl-2-butene base, n-hexyl, phenmethyl, cinnamyl.
The above-mentioned Asian puccoon ketoximes derivatives of the present invention is with 1,4,5,8-tetramethoxy naphthaldehyde is a raw material, through reacting with the isopentene zinc bromide, introduces Shikonin six carbon side chains, again pendant hydroxyl group is carried out oxidation and get carbonyl compound, then with oxammonium hydrochloride reaction, again with the oxime that generates with different haloalkane etherificates, 2-replacement-1,4,5,8-tetramethoxy naphthalene is after cerous ammonium nitrate (CAN) oxidation demethylation gets target compound.Use above method to synthesize 11 target compounds altogether, the structure of target compound sees Table 1.
The structure (spectral data is seen embodiment) of table 1 Asian puccoon ketoximes derivatives
Measuring the growth-inhibiting effect of different concns lower section compound to human lung cancer cell A549 and human leukemia cell HL-60, the results are shown in table 2 and the table 3.Experimental result shows that all tested Asian puccoon ketoximes derivatives all have certain tumour cell restraining effect in the concentration range of experiment.
Table 2 Asian puccoon ketoximes derivatives is to the inhibiting rate (%) of A549 human lung carcinoma cell growth
Table 3 Asian puccoon ketoximes derivatives is to the inhibiting rate (%) of HL-60 human leukemia cell growth
The present invention is oxidized to the side chain alcoholic extract hydroxyl group of Shikonin ketone and makes oxime ether, and on the one hand, the hydroxyl of side chain in the original Shikonin structure is sheltered in the introducing of carbonyl oxime; On the other hand, the polarity of oxime is stronger, can improve the wetting ability of compound.In addition, methylating of naphthazarin parent nucleus hydroxyl can be sheltered the toxic side effect that causes with complexing of metal ion.The pharmacological results of the present invention shows that institute's synthetic compound all has the effect of certain inhibition growth of tumour cell, compares with the parent compound Shikonin, may make its cytotoxicity reduction widely, water-soluble improving.
Description of drawings
Fig. 1 is The compounds of this invention synthetic line figure
Embodiment
Below embodiments of the invention are elaborated: present embodiment is being to implement under the prerequisite with the technical solution of the present invention, provided detailed embodiment and concrete operating process, but protection scope of the present invention is not limited to following embodiment.
As shown in Figure 1, Asian puccoon ketoximes derivatives of the present invention is with 1,4,5,8-tetramethoxy naphthaldehyde 1 is a raw material, through reacting with the isopentene zinc bromide, introduce Shikonin six carbon side chains, again pendant hydroxyl group is carried out oxidation and get carbonyl compound 3, react with oxammonium hydrochloride then, again with the different haloalkane etherificate of oxime 4 usefulness that generates, get 2-and replace-1,4,5,8-tetramethoxy naphthalene 5-14 is after cerous ammonium nitrate (CAN) oxidation demethylation gets target compound 15-24.
Embodiment 1
2-(1-hydroxy-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 2
Under the nitrogen protection, activated zinc powder (5g 0.077mol) places exsiccant tetrahydrofuran (THF) (100ml), dripping bromine for isopentene (4ml, 0.035mol), reaction solution stirring at room 1 hour, the elimination zinc powder is standby.
1,4,5,8-tetramethoxy naphthalene-2-formaldehyde (1.38g, 0.005mol) be dissolved in (50ml) in the exsiccant tetrahydrofuran (THF), add the above-mentioned isopentene zinc bromide for preparing, stirring at room is after 1 hour, add HMPA (10ml), steam tetrahydrofuran (THF), reacted 10 hours down at 130 ℃.After the reaction solution cooling, add saturated aqueous ammonium chloride, with ethyl acetate (30ml * 3) extraction, the saturated common salt water washing, anhydrous magnesium sulfate drying steams solvent, get crude product, column chromatography for separation (ether: normal hexane=1: 2) get 1.42g yellow oil, yield 82%.
1H?NMR(CDCl
3)δ：7.02(s，1H)，6.82(d，2H)，5.24(m，2H)，3.99(s，3H)，3.93(s，3H)，3.91(s，3H)，3.76(s，3H)，2.53(m，2H)，1.72(s，3H)，1.66(s，3H).
2-(1-oxo-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 3
2-(1-hydroxy-4-methyl-3-pentenyl)-1,4,5, (3.46g 0.01mol) is dissolved in the methylene dichloride (100ml) 8-tetramethoxy naphthalene 2, and (4.66g, 0.011mol), stirring at room is after 4 hours, stopped reaction to add the Dess-Martin oxygenant.Add saturated sodium bicarbonate solution (80ml), stir after 10 minutes, tell organic layer, water layer merges organic layer with dichloromethane extraction (50ml * 3), the saturated common salt water washing, anhydrous magnesium sulfate drying steams solvent, gets crude product, column chromatography for separation (ether: normal hexane=2: 1) get glassy yellow oily matter 2.66g, yield 77%.
1H?NMR(CDCl
3)δ：6.93(m，3H)，5.48(t，J＝7.2Hz，1H)，3.98(s，3H)，3.95(s，3H)，3.90(s，3H)，3.85(d，J＝6.9Hz，2H)，3.78(s，3H)，1.76(s，3H)，1.65(s，3H).ESI-MS?m/z?399.05(M+CH
3OH+Na)
+.
2-(1-oxyimino-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 4
2-(1-oxo-4-methyl-3-pentenyl)-1,4,5, (1.72g 0.005mol) is dissolved in the ethanol (70ml) 8-tetramethoxy naphthalene 3, and (0.70g 0.01mol) and pyridine (2ml), refluxes after 0.5 hour stopped reaction to add oxammonium hydrochloride.Be chilled to room temperature, boil off ethanol, add methylene dichloride (30ml) and water (30ml) in the residue, jolting, tell organic layer, water layer merges organic layer with dichloromethane extraction (30ml * 2), the saturated common salt water washing, anhydrous magnesium sulfate drying steams solvent, gets crude product, column chromatography for separation (ether: normal hexane=1: 1) get nearly colorless oil 1.45g, yield 81%.
1H NMR (CDCl
3) δ: 6.85 (s, 2H), 6.72
a, 6.58
b(s, 1H), 5.25
a, 5.16
b(t, J=7.2Hz, 1H), 3.96 (s, 3H), 3.93 (s, 3H), 3.91 (s, 3H), 3.80
a, 3.77
b(s, 3H), 3.60
a, 3.33
b(d, J=7.2Hz, 2H), 1.67
a, 1.60
b(s, 3H), 1.52 (s, 3H). (a represents E-isomer, and b represents Z type isomer)
2-(1-alkoxyimino-4-methyl-3-pentenyl)-1,4,5, the synthetic logical method of 8-tetramethoxy naphthalene 5-14
2-(1-oxyimino-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene (0.5mmol) is dissolved in the methylene dichloride (7ml), the potassium hydroxide solution (7ml), Tetrabutyl amonium bromide (0.05g) and the haloalkane (1.5mmol) that add 1M after 5 hours, are chilled to room temperature in 40 ℃ of reactions, add suitable quantity of water, organic layer is told in jolting, water layer dichloromethane extraction (5ml * 2), merge organic layer, the saturated common salt water washing, anhydrous magnesium sulfate drying steams solvent, get crude product, column chromatography for separation gets faint yellow oily thing.
2-(1-methoxyimino-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 5
Yield 71%.
1H NMR (CDCl
3) δ: 6.85 (s, 2H), 6.72
a, 6.58
b(s, 1H), 5.21
a, 5.15
b(t, J=7.2Hz, 1H), 4.01 (s, 3H), 3.95 (s, 3H), 3.94 (s, 3H), 3.90 (s, 3H), 3.84
a, 3.77
b(s, 3H), 3.55
a, 3.32
b(d, J=7.2Hz, 2H), 1.64
a, 1.60
b(s, 3H), 1.50
a, 1.45
b(s, 3H). (a represents E-isomer, and b represents Z type isomer)
2-(1-ethoxy imino-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 6
Yield 68%.
1H NMR (CDCl
3) δ: 6.84 (s, 2H), 6.72
a, 6.53
b(s, 1H), 5.17
a, 5.15
b(t, J=7.2Hz, 1H), 4.26
a, 4.10
b(q, J=6.9Hz, 2H), 3.94 (s, 3H), 3.93 (s, 3H), 3.89 (s, 3H), 3.77 (s, 3H), 3.56
a, 3.33
b(d, J=7.2Hz, 2H), 1.63
a, 1.61
b(s, 3H), 1.51
a, 1.45
b(s, 3H), 1.35
a, 1.21
b(t, J=7.2Hz, 2H). (a represents E-isomer, and b represents Z type isomer)
2-(1-third oxyimino group-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 7
Yield 67%.
1H NMR (CDCl
3) δ: 6.84 (s, 2H), 6.71
a, 6.53
b(s, 1H), 5.15
a, 5.14
b(t, J=7.2Hz, 1H), 4.16
a, 3.99
b(t, J=6.6Hz, 2H), 3.94 (s, 3H), 3.92 (s, 3H), 3.90 (s, 3H), 3.76 (s, 3H), 3.55
a, 3.32
b(d, J=7.5Hz, 2H), 1.75 (m, 2H), 1.62
a, 1.60
b(s, 3H), 1.50
a, 1.45
b(s, 3H), 1.00
a, 0.84
b(d, J=7.5Hz, 2H). (a represents E-isomer, and b represents Z type isomer)
2-(1-isopropyl oxygen imino-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 8
Yield 64%.
1H NMR (CDCl
3) δ: 6.82 (s, 2H), 6.70
a, 6.53
b(s, 1H), 5.15
a, 5.13
b(t, J=7.2Hz, 1H), 4.47
a, 4.33
b(m, 1H), 3.93 (s, 3H), 3.91 (s, 3H), 3.88 (s, 3H), 3.75 (s, 3H), 3.52
a, 3.32
b(d, J=7.2Hz, 2H), 1.60
a, 1.58
b(s, 3H), 1.50
a, 1.44
b(s, 3H), 1.31
a, 1.15
b(d, J=6.6Hz, 6H). (a represents E-isomer, and b represents Z type isomer)
2-(1-fourth oxyimino group-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 9
Yield 69%.
1H NMR (CDCl
3) δ: 6.84 (s, 2H), 6.71
a, 6.53
b(s, 1H), 5.17
a, 5.14
b(t, J=7.2Hz, 1H), 4.20
a, 4.03
b(t, J=6.9Hz, 2H), 3.94 (s, 3H), 3.92 (s, 3H), 3.90 (s, 3H), 3.76 (s, 3H), 3.54
a, 3.32
b(d, J=6.9Hz, 2H), 1.72 (m, 2H), 1.62
a, 1.60
b(s, 3H), 1.50
a, 1.45
b(s, 3H), 1.27 (m, 2H), 0.97
a, 0.85
b(d, J=7.2Hz, 2H). (a represents E-isomer, and b represents Z type isomer)
2-(1-penta oxyimino group-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 10
Yield 70%.
1H NMR (CDCl
3) δ: 6.84 (s, 2H), 6.71
a, 6.53
b(s, 1H), 5.19
a, 5.17
b(t, J=7.2Hz, 1H), 4.21
a, 4.04
b(t, J=6.6Hz, 2H), 3.95 (s, 3H), 3.93 (s, 3H), 3.91 (s, 3H), 3.77 (s, 3H), 3.55
a, 3.33
b(d, J=7.2Hz, 2H), 1.75 (m, 2H), 1.63
a, 1.60
b(s, 3H), 1.51
a, 1.46
b(s, 3H), 1.27 (m, 4H), 0.97
a, 0.85
b(d, J=7.2Hz, 2H). (a represents E-isomer, and b represents Z type isomer)
2-(1-(3-methyl-pentenyl) oxyimino group-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 11
Yield 64%.
1H NMR (CDCl
3) δ: 6.84 (s, 2H), 6.73
a, 6.54
b(s, 1H), 5.52
a, 5.33
b(t, J=7.5Hz, 1H), 5.20
a, 5.14
b(t, J=7.2Hz, 1H), 4.72
a, 4.55
b(t, J=6.9Hz, 2H), 3.94 (s, 3H), 3.93 (s, 3H), 3.90 (s, 3H), 3.77 (s, 3H), 3.56
a, 3.33
b(d, J=7.2Hz, 2H), 1.79
a, 1.75
b(s, 3H), 1.69
a, 1.66
b(s, 3H), 1.64
a, 1.60
b(s, 3H), 1.50
a, 1.46
b(s, 3H). (a represents E-isomer, and b represents Z type isomer)
2-(the own oxyimino group of 1--4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 12
Yield 65%.
1H NMR (CDCl
3) δ: 6.84 (s, 2H), 6.72
a, 6.52
b(s, 1H), 5.18
a, 5.15
b(t, J=7.2Hz, 1H), 4.21
a, 4.03
b(t, J=6.6Hz, 2H), 3.95 (s, 3H), 3.93 (s, 3H), 3.90 (s, 3H), 3.77 (s, 3H), 3.55
a, 3.32
b(d, J=7.5Hz, 2H), 1.74 (m, 2H), 1.63
a, 1.61
b(s, 3H), 1.51
a, 1.45
b(s, 3H), 1.22 (m, 6H), 0.92
a, 0.84
b(d, J=6.6Hz, 2H). (a represents E-isomer, and b represents Z type isomer)
2-(1-benzene methoxyimino-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 13
Yield 63%.
1H NMR (CDCl
3) δ: 7.42-7.28 (m, 5H), 6.82 (s, 2H), 6.66
a, 6.44
b(s, 1H), 5.26
a, 5.09
b(s, 2H), 5.17
a, 5.15
b(t, J=7.2Hz, 1H), 3.92 (s, 3H), 3.89 (s, 3H), 3.82 (s, 3H), 3.69
a, 3.63
b(s, 3H), 3.57
a, 3.31
b(d, J=7.2Hz, 2H), 1.61
a, 1.59
b(s, 3H), 1.46
a, 1.43
b(s, 3H). (a represents E-isomer, and b represents Z type isomer)
2-(1-Chinese cassia tree oxyimino group-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene 14
Yield 67%.
1H NMR (CDCl
3) δ: 7.42-7.29 (m, 5H), 6.83 (s, 2H), 6.71
a, 6.55
b(s, 1H), 6.68
a, 6.52
b(d, J=15.9Hz, 1H), 6.45
a, 6.35
b(t, J=15.9Hz, J=7.2Hz, 1H), 5.19
a, 5.17
b(t, J=7.2Hz, 1H), 4.88
a, 4.71
b(d, J=5.7Hz, 2H), 3.93 (s, 3H), 3.89 (s, 3H), 3.87 (s, 3H), 3.77
a, 3.75
b(s, 3H), 3.60
a, 3.32
b(d, J=7.5Hz, 2H), 1.63
a, 1.61
b(s, 3H), 1.51
a, 1.45
b(s, 3H). (a represents E-isomer, and b represents Z type isomer)
Embodiment 5
6-(1-alkoxyimino-4-methyl-3-pentenyl)-5,8-dimethoxy-1, the synthetic logical method of 4-naphthoquinones 15-24
2-(1-alkoxyimino-4-methyl-3-pentenyl)-1,4,5,8-tetramethoxy naphthalene (0.20mmol) is dissolved in the acetonitrile (3ml), drips the aqueous solution (2ml) of ceric ammonium nitrate (0.50mmol).Reaction solution is in stirring at room after 10 minutes, dilute with water, and dichloromethane extraction, the saturated common salt washing, anhydrous magnesium sulfate drying steams solvent, and the preparation Thin-layer separation gets yellow oil.
6-(1-methoxyimino-4-methyl-3-pentenyl)-5,8-dimethoxy-1,4-naphthoquinones 15
Yield 68%.
1H NMR (CDCl
3) δ: 7.23
a, 6.99
b(s, 1H), 6.85 (s, 2H), 5.20
a, 5.10
b(t, J=7.2Hz, 1H), 4.05
a, 4.03
b(s, 3H), 3.99 (s, 3H), 3.88
a, 3.84
b(s, 3H), 3.53
a, 3.28
b(d, J=7.2Hz, 2H), 1.72
a, 1.66
b(s, 3H), 1.56
a, 1.52
b(s, 3H). (a represents E-isomer, and b represents Z type isomer) .ESI-MS m/z398.05 (M+CH
3OH+Na)
+.
6-(1-ethoxy imino-4-methyl-3-pentenyl)-5,8-dimethoxy-1,4-naphthoquinones 16
Yield 74%.
1H NMR (CDCl
3) δ: 7.24
a, 7.01
b(s, 1H), 6.87 (s, 2H), 5.21
a, 5.12
b(t, J=7.2Hz, 1H), 4.32
a, 4.16
b(q, J=7.2Hz, 2H), 4.04
a, 4.01
b(s, 3H), 3.86 (s, 3H), 3.55
a, 3.30
b(d, J=7.2Hz, 2H), 1.72
a, 1.68
b(s, 3H), 1.59
a, 1.53
b(s, 3H), 1.40
a, 1.25
b(t, J=7.2Hz, 3H) (a represents E-isomer, and b represents Z type isomer) .ESI-MS m/z 412.10 (M+CH
3OH+Na)
+.
6-(1-third oxyimino group-4-methyl-3-pentenyl)-5,8-dimethoxy-1,4-naphthoquinones 17
Yield 62%.
1H NMR (CDCl
3) δ: 7.19
a, 6.96
b(s, 1H), 6.81 (s, 2H), 5.15
a, 5.08
b(t, J=7.2Hz, 1H), 4.17
a, 4.02
b(q, J=6.6Hz, 2H), 3.99
a, 3.95
b(s, 3H), 3.78 (s, 3H), 3.50
a, 3.25
b(d, J=7.2Hz, 2H), 1.75
a, 1.67
b(m, 2H), 1.63
a, 1.60
b(s, 3H), 1.54
a, 1.48
b(s, 3H), 1.01
a, 0.86
b(t, J=7.5Hz, 3H) (a represents E-isomer, and b represents Z type isomer)
6-(1-isopropyl oxygen imino-4-methyl-3-pentenyl)-5,8-dimethoxy-1,4-naphthoquinones 18
Yield 61%.
1H NMR (CDCl
3) δ: 7.17
a, 6.96
b(s, 1H), 6.82 (s, 2H), 5.14
a, 5.10
b(t, J=7.2Hz, 1H), 4.47
a, 4.36
b(m, 1H), 3.99
a, 3.95
b(s, 3H), 3.80 (s, 3H), 3.48
a, 3.25
b(d, J=7.5Hz, 2H), 1.66
a, 1.62
b(s, 3H), 1.54
a, 1.48
b(s, 3H), 1.32
a, 1.16
b(d, J=6.6Hz, 6H) (a represents E-isomer, and b represents Z type isomer) .ESI-MS m/z 394.15 (M+Na)
+.
6-(1-fourth oxyimino group-4-methyl-3-pentenyl)-5,8-dimethoxy-1,4-naphthoquinones 19
Yield 68%.
1H NMR (CDCl
3) δ: 7.17
a, 6.99
b(s, 1H), 6.81 (s, 2H), 5.13
a, 5.07
b(t, J=7.5Hz, 1H), 4.20
a, 4.04
b(q, J=6.6Hz, 2H), 3.98
a, 3.93
b(s, 3H), 3.79 (s, 3H), 3.48
a, 3.24
b(d, J=7.2Hz, 2H), 1.68 (m, 4H), 1.66
a, 1.61
b(s, 3H), 1.52
a, 1.46
b(s, 3H), 0.96
a, 0.87
b(t, J=7.2Hz, 3H) (a represents E-isomer, and b represents Z type isomer) .ESI-MS m/z 408.10 (M+Na)
+.
6-(1-penta oxyimino group-4-methyl-3-pentenyl)-5,8-dimethoxy-1,4-naphthoquinones 20
Yield 72%.
1H NMR (CDCl
3) δ: 7.17
a, 6.94
b(s, 1H), 6.81 (s, 2H), 5.13
a, 5.06
b(t, J=7.5Hz, 1H), 4.19
a, 4.02
b(t, J=6.6Hz, 2H), 3.98
a, 3.93
b(s, 3H), 3.79
a, 3.78
b(s, 3H), 3.48
a, 3.23
b(d, J=7.2Hz, 2H), 1.72
a, 1.58
b(m, 2H), 1.65
a, 1.61
b(s, 3H), 1.52
a, 1.46
b(s, 3H), 1.39
a, 1.27
b(m, 4H), 0.92
a, 0.84
b(t, J=7.2Hz, 3H). (a represents E-isomer, and b represents Z type isomer) .ESI-MS m/z 454.10 (M+CH
3OH+Na)
+.
6-(1-(3-methyl-pentenyl) oxyimino group-4-methyl-3-pentenyl)-5,8-dimethoxy-1,4-naphthoquinones 21
Yield 69%.
1H NMR (CDCl
3) δ: δ: 7.17
a, 6.94
b(s, 1H), 6.80 (s, 2H), 5.46
a, 5.29
b(t, J=7.5Hz, 1H), 5.14
a, 5.07
b(t, J=7.2Hz, 1H), 4.69
a, 4.53
b(d, J=7.2Hz, 2H), 3.97
a, 3.93
b(s, 3H), 3.79
a, 3.78
b(s, 3H), 3.48
a, 3.23
b(d, J=7.2Hz, 2H), 1.77
a, 1.73
b(s, 3H), 1.69
a, 1.65
b(s, 3H), 1.63
a, 1.60
b(s, 3H), 1.50
a, 1.45
b(s, 3H). (a represents E-isomer, and b represents Z type isomer) .ESI-MS m/z 420.05 (M+Na)
+.
6-(the own oxyimino group of 1--4-methyl-3-pentenyl)-5,8-dimethoxy-1,4-naphthoquinones 22
Yield 67%.
1H NMR (CDCl
3) δ: 7.17
a, 6.94
b(s, 1H), 6.80 (s, 2H), 5.13
a, 5.07
b(t, J=7.2Hz, 1H), 4.19
a, 4.02
b(t, J=6.9Hz, 2H), 3.98
a, 3.93
b(s, 3H), 3.79 (s, 3H), 3.48
a, 3.23
b(d, J=7.2Hz, 2H), 1.71 (m, 2H), 1.66
a, 1.61
b(s, 3H), 1.52
a, 1.46
b(s, 3H), 1.33 (m, 4H), 1.25 (m, 2H), 0.90
a, 0.84
b(t, J=7.2Hz, 3H). (a represents E-isomer, and b represents Z type isomer) .ESI-MS m/z 436.10 (M+Na)
+.
6-(1-benzene methoxyimino-4-methyl-3-pentenyl)-5,8-dimethoxy-1,4-naphthoquinones 23
Yield 61%.
1H NMR (CDCl
3) δ: 7.43-7.30 (m, 5H), 7.12
a, 6.86
b(s, 1H), 6.80 (s, 2H), 5.26
a, 5.08
b(s, 2H), 5.12 (t, J=7.2Hz, 1H), 3.95
a, 3.87
b(s, 3H), 3.70
a, 3.68
b(s, 3H), 3.52
a, 3.25
b(d, J=7.5Hz, 2H), 1.66
a, 1.62
b(s, 3H), 1.50
a, 1.46
b(s, 3H). (a represents E-isomer, and b represents Z type isomer) .ESI-MS m/z 442.10 (M+Na)
+.
6-(1-Chinese cassia tree oxyimino group-4-methyl-3-pentenyl)-5,8-dimethoxy-1,4-naphthoquinones 24
Yield 61%.
1H NMR (CDCl
3) δ: 7.40-7.29 (m, 5H), 7.18
a, 6.98
b(s, 1H), 6.80 (s, 2H), 6.70
a, 6.57
b(d, J=16.2Hz, 1H), 6.42
a, 6.30
b(t, J=16.2Hz, J=7.2Hz, 1H), 5.16
a, 5.13
b(t, J=7.2Hz, 1H), 4.88
a, 4.71
b(d, J=6.3Hz, 2H), 3.95
a, 3.93
b(s, 3H), 3.82
a, 3.79
b(s, 3H), 3.54
a, 3.26
b(d, J=7.2Hz, 2H), 1.67
a, 1.63
b(s, 3H), 1.54
a, 1.48
b(s, 3H). (a represents E-isomer, and b represents Z type isomer) .ESI-MS m/z 468.10 (M+Na)
+
Claims (1)
1. one kind can be used for antineoplastic Asian puccoon ketoximes derivatives, it is characterized in that, is 5 of 6-replacement, 8-dimethoxy-1, and the 4-naphthoquinone derivatives, general structure is as follows:
R is a hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, n-pentyl, 3-methyl-2-butene base, n-hexyl, phenmethyl, cinnamyl.
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| CN1374288A (en) * | 2002-03-19 | 2002-10-16 | 中山大学 | Gronwell naphthaquinone derivative and its application in preparing anticancer medicine |
| CN1690044A (en) * | 2004-04-23 | 2005-11-02 | 中国科学院上海药物研究所 | 5,8-menadiol diacetate derivatives and their preparing process and use |
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| CN1690044A (en) * | 2004-04-23 | 2005-11-02 | 中国科学院上海药物研究所 | 5,8-menadiol diacetate derivatives and their preparing process and use |
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