CN103012360B - Snail dinaphthalene compound, preparation method and application thereof - Google Patents
Snail dinaphthalene compound, preparation method and application thereof Download PDFInfo
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- CN103012360B CN103012360B CN201210586862.8A CN201210586862A CN103012360B CN 103012360 B CN103012360 B CN 103012360B CN 201210586862 A CN201210586862 A CN 201210586862A CN 103012360 B CN103012360 B CN 103012360B
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- 0 C*CCC1C*CC1 Chemical compound C*CCC1C*CC1 0.000 description 3
- RILSFTHCVOMUNG-UHFFFAOYSA-N COc(cc1)c(C(CCC2=O)(O3)OC4=CC=CC5=CCCC3=C45)c2c1O Chemical compound COc(cc1)c(C(CCC2=O)(O3)OC4=CC=CC5=CCCC3=C45)c2c1O RILSFTHCVOMUNG-UHFFFAOYSA-N 0.000 description 1
- OEKIHDOSZSACCB-UHFFFAOYSA-N C[IH]COc1cc(C(CCC2)(O3)Oc4cccc5c4c3ccc5)c2cc1OCCN Chemical compound C[IH]COc1cc(C(CCC2)(O3)Oc4cccc5c4c3ccc5)c2cc1OCCN OEKIHDOSZSACCB-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention provides a snail dinaphthalene compound with a structure general formula WM. In the formula, R1 and R2 independently represent H, methyl or acetyl. The invention also provides a preparation method of the compound and an application as an agricultural fungicide. The result shows that the compound provided by the invention has good bactericidal effects on seven plant pathogenic bacterium comprising rice rhizoctonia solani, macrophoma kawatsukai, botrytis cinerea, fusarium vasinfectum, phomopasis asparagi, fusarium graminearum schw and peanut mycosphaerella arachidicola.
Description
Technical field
The present invention relates to a kind of spiral shell two naphthalene compounds, preparation method and application thereof, belong to agrochemical field.
Background technology
Spiral shell dinaphthyl Palmarumycin CP17 and Palmarumycin CP18 be Martinez-Luis in 2008 etc. from Panama a kind of endophyte of plant Edenia sp. fermented liquid, be separated to there is the graceful worm activity of good anti-Li Shi and the extremely low natural organic-compound of cytotoxicity, Palmarumycin CP17 and Palmarumycin CP18 are respectively 1.34 and 0.62 μ M to the IC50 value of the graceful worm of Li Shi, there is wide application prospect [1,2] in medical research field.2009 Nian Ben seminars also report the strain endophyte Dzf12 fermented liquid being separated to from China medicinal plant Rhizome of Peltate Yam Dioscorea zingiberensis and separate and obtain Palmarumycin CP17 and diepoxin κ, η, κ, ζ, γ, and finding the mixture of Diepoxin η and Diepoxin ζ, Diepoxin κ is to intestinal bacteria, Agrobacterium tumefaciems, tomato Streptomyces scabies, avenae subsp.citrull, subtilis etc. have certain inhibition activity [3,4].
Bibliographical information some natural spiral shell dinaphthyl Palmarumycins complete synthesis, as Palmarumycin CP1, CP2, C2, C11, C12, diepoxin σ, CJ12371, CJ12372 etc., but about the synthesizing of non-natural product of spiral shell dinaphthyl Palmarumycins only seen Wipf synthetic and their anti-tumor activities [5-7] to the cancer cells such as MCF-7 and MDA-MF-231 to Palmarumycin CP1 analogue, and Krohn is to the synthetic of Palmarumycin CP1 and CP2 analogue and they are to intestinal bacteria, the inhibition activity [8] of genus bacillus and Sarcodon fuligineo-violaceum, but at present also not about Palmarumycin CP17 and analogue is synthetic and the research report of agricultural bactericidal activity.Therefore the applicant has carried out the research of the synthetic and agricultural bactericidal activity of the complete synthesis and analogue of Palmarumycin CP17.
Summary of the invention
The object of this invention is to provide the spiro-dinaphthyl compound that a kind of general structure is WM.
Another object of the present invention is to provide the preparation method of spiro-dinaphthyl compound.
Still a further object of the present invention is to provide the application of spiro-dinaphthyl compound in disinfectant use in agriculture.
In order to realize the object of the invention, the invention provides a kind of spiro-dinaphthyl compound with general structure WM and be:
R in formula
1and R
2represent independently of one another H, methyl or ethanoyl.
Preferably R
1during for H, R
2for H or methyl; R
1during for methyl, R
2be all methyl; R
1during for ethanoyl, R
2for methyl or ethanoyl; Further preferred R
1with R
2be all methyl; R
1during for ethanoyl, R
2for methyl.
The present invention also provides the preparation method of spiro-dinaphthyl compound WM, comprises the steps:
1)
with Succinic anhydried at anhydrous AlCl
3the lower reaction of effect, generates
2)
under alkaline condition, oil bath heating generates with hydrazine hydrate
3)
cyclization reagent PPA reacts with pass, generates
4)
with pyridine tosilate, 1, the reaction of 8-dihydroxy naphthlene generates
5)
obtain through oxidizing reaction the spiro-dinaphthyl compound that general formula is WM
R in formula
1and R
2define the same.
Described step 1) is under ice-water bath condition, to add anhydrous AlCl in batches
3;
Described step 2) be that reaction refluxes 4 ~ 5 hours under 135 ~ 145 DEG C of conditions, continue to be warming up to 200 ~ 220 DEG C to steam except unnecessary hydrazine hydrate, then be cooled to 190 ~ 200 DEG C of reactions 4 ~ 5 hours; Described hydrazine hydrate concentration is 85%;
Described step 3) is to react 0.5 ~ 1 hour under 70 ~ 80 DEG C of conditions.
In described step 5)
under the effect of dichromic acid pyridinium, carry out oxidizing reaction with peroxy tert-butyl alcohol, generate
Described
demethylation obtains compound
In described step 5), when
while being 5,8-dimethoxy-1-tetralone Spiroketals, with (CH
3)
3siI in molar ratio 1:10 ~ 11 hybrid reaction, again through the oxidation of phenolic hydroxyl group esterification, benzyl position, generate
When
while being 5,8-dimethoxy-1-tetralone Spiroketals with (CH
3)
3siI in molar ratio 1:5 ~ 6 hybrid reaction, again through the oxidation of phenolic hydroxyl group esterification, benzyl position, generate
Described
under alkaline condition, hydrolysis generates
Described
under alkaline condition, hydrolysis generates
Spiro-dinaphthyl compound prepared by the present invention can also be served as disinfectant use in agriculture.
The compound that is WM by general formula is dissolved in and in solvent, is mixed with certain density solution or preparation carries out biological activity test, result shows that general formula is that the compound of WM is to rice wilt pathogens, Botryosphaeria berengeriana f. sp, botrytis cinerea, cotton-wilt fusarium, asparagus stem is withered, and fusarium graminearum and peanut Cercospora bacteria seven kind of plant pathogenic bacterias have good germicidal action.
Embodiment
Following examples are used for illustrating the present invention, but are not used for limiting the scope of the invention.
Embodiment 14-(2,5-Dimethoxyphenyl)-4-ketobutyric acid (1a)
and 4-(3,4-Dimethoxyphenyl)-4-ketobutyric acid (1b)
synthetic
In the there-necked flask of 500mL, add 20g(0.15mol) Isosorbide-5-Nitrae-dimethoxy benzene, 15g(0.15mol) Succinic anhydried, 200mL CH
2clCH
2cl with each 10g, adds common 40g(0.3mol under the condition of ice-water bath in batches) pulverous anhydrous AlCl
3; Then remove ice-water bath, room temperature reaction 24h under mechanical stirring condition.After completion of the reaction, reaction solution is poured in the acid of 200mL cryosel and fully stirred rear stratification, separate organic phase, and be extracted with ethyl acetate water, will after organic phase merging, use anhydrous MgSO
4after dry, be spin-dried for solvent, obtain the crude product of faint yellow solid, then use respectively 1mol/L HCl and petroleum ether crude product, obtain the compound 1a that 26g is pure, yield 76% after washing away raw material.
After testing, m.p.98-99 DEG C.
1H?NMR(CDCl
3)δ:2.75(t,J=6.5Hz,2H),3.47(t,J=6.5Hz,2H),3.79(s,3H),3.88(s,3H),6.92(d,J=9.0Hz,1H),7.05(dd,J=3.2Hz,9.0Hz,1H),7.35(d,J=3.2Hz,1H);ESI-MS(+)m/z:261.1。
Adopting same procedure is that raw material obtains compound 1b with 1,2-dimethoxy benzene, yield 79%.
After testing, m.p.160-162 DEG C.
1H?NMR(CDCl
3)δ:2.80(t,J=6.0Hz,2H),3.29(t,J=6.0Hz,2H),3.94(s,3H),3.95(s,3H),6.90(d,J=8.5Hz,1H),7.54(d,J=2.4Hz,1H),7.62(dd,J=2.4Hz,8.5Hz,1H);ESI-MS(+)m/z:261.1。
Embodiment 24-(2,5-Dimethoxyphenyl)-butyric acid (2a)
and 4-(3,4-Dimethoxyphenyl)-butyric acid (2b)
synthetic
In 500mL there-necked flask, add 12.5g(52mmol) 4-(2,5-Dimethoxyphenyl)-4-ketobutyric acid 1a, 8g (200mmol) NaOH, 8mL(160mmol) 85% hydrazine hydrate and 200mL dimerization triethylene glycol; Add air set pipe, after the device such as fluid-tight and thermometer, stir and oil bath heating, under 140 DEG C of conditions, react backflow 4h, then remove prolong, oil bath temperature is risen to 210 DEG C to steam except unnecessary hydrazine hydrate, add prolong, continue to add slowly a small amount of water to make temperature be down to 195 DEG C in the backward system of reaction 1h, and under this temperature condition, continue to stop heating after reaction 4h.In the time that temperature is down to room temperature, reaction solution is poured into after regulating its pH to 4～5 in 200mL water and with HCl and used extracted with diethyl ether.Merge ether and use afterwards mutually anhydrous Na
2sO
4after dry, filter, obtain to suction filtration after adding in filtrate 4g NaOH vigorous stirring to make in liquid phase TLC detect there is no product point in batches the sodium salt that solid is product, then solid being neutralized to pH with 5M HCl is that 4～5 rear leaving standstill are separated out product, after suction filtration is dry, obtain 8.4g compound 2a, yield 72%.
After testing, m.p.64-65 DEG C.
1H?NMR(CDCl
3)δ:1.93(m,2H),2.37(t,J=7.6Hz,2H),2.65(t,J=7.6Hz,2H),3.76(s,3H),3.77(s,3H),6.69-6.75(m,3H);ESI-MS(+)m/z:247.1[M+Na]+。
Adopt same procedure to obtain compound 2b, yield 75% taking 1b as raw material.
After testing, m.p.45-47 DEG C.
1H?NMR(CDCl
3)δ:1.90-1.99(m,2H),2.33-2.40(m,2H),2.56-2.65(m,2H),3.69(s,1H),3.85(s,3H),3.87(s,3H),6.66-6.81(m,3H);ESI-MS(+)m/z:247.1[M+Na]+。
Embodiment 35,8-dimethoxy-1-tetralone (3a)
with 6,7-dimethoxy-1-tetralone (3b)
synthetic
In 150mL there-necked flask, add 30mL85%H
3pO
4, 46g P
2o
5fully stirring lower oil bath is heated to 80 DEG C of about half hours and it is generated close cyclization reagent PPA, then in bottle, add 3.9g(17mmol) 4-(2,5-Dimethoxyphenyl) butyric acid 2a, reaction solution becomes scarlet at once, and stopped reaction after 80 DEG C of reaction 0.5h, pours reaction solution in frozen water into and stir, then use extracted with diethyl ether, collect ether and use respectively afterwards mutually saturated Na
2cO
3then the each washing of solution and water uses anhydrous Na three times
2sO
4after dry, be spin-dried for and obtain 2.9g compound 3a, yield 77%.
After testing, m.p.57-58 DEG C.
1H?NMR(CDCl
3)δ:2.01-2.10(m,2H),2.59-2.64(m,2H),2.88(t,J=6.2Hz,2H),3.82(s,3H),3.86(s,3H),6.80(d,J=9.0Hz,1H),6.99(d,J=9.0Hz,1H);ESI-MS(+):m/z207.1[M+H]
+。
Adopt same procedure to obtain compound 3b, yield 75% taking 2b as raw material.
After testing, m.p.94-95 DEG C.
1H?NMR(CDCl
3);δ:2.08-2.17(m,2H),2.60(t,J=6.5Hz,2H),2.90(t,J=6.3Hz,2H),3.92(s,3H),3.94(s,3H),6.68(s,1H),7.52(s,1H)。
Embodiment 4 spiral shell dinaphthyl framework compounds 5,8-dimethoxy-1-tetralone Spiroketals (4a)
with 6,7-dimethoxy-1-tetralone Spiroketals (4b)
synthetic
In 250mL there-necked flask; add 100mL anhydrous methanol; 25mL trimethyl orthoformate; 1.1g(5.3mmol) 5; 8-dimethoxy-1 tetralone 3a and 270mg(0.98mmol) pyridine tosilate (PPTS), after then system being vacuumized, pass into nitrogen protection, stirring reaction under room temperature; after 24h, add 12mL trimethyl orthoformate, continue to add 0.22mL triethylamine stopped reaction in the backward reaction solution of room temperature reaction 16h.Then solvent was concentrated to neutral alumina column, elutriant is ethyl acetate: sherwood oil=1:1, separates and obtains 1.08g product Isosorbide-5-Nitrae, 5-trimethoxy-7,8-dihydronaphthalene, yield 92.3%, white solid.
After testing,
1h NMR (CDCl
3) δ: 2.17 (m, 2H), 2.67 (t, J=8Hz, 2H), 3.64 (s, 3H), 3.79 (s, 6H), 5.13 (t, J=5Hz, 1H), 6.76 (d, J=9Hz, 1H), 6.79 (d, J=9Hz, 1H).
In 500mL there-necked flask; add 7.0g(32mmol) 1; 4; 5-trimethoxy-7; 8-dihydronaphthalene; 5.6g (35mmol) 1; 8-dihydroxy naphthlene; 700mg (4mmol) p-methyl benzenesulfonic acid and 350mL toluene, and the apparatus,Soxhlet's and the return line that fill up 4A molecular sieve are installed, then system is vacuumized and passes into nitrogen protection; heating makes the stable backflow of toluene; reaction stops heating after 42h, when question response liquid is cooled to room temperature, is diluted with ether, then uses anhydrous Na with after saturated sodium bicarbonate solution washing 2 times
2sO
4-dry, separated concentrating neutral alumina column after dried solution filter, elutriant is ethyl acetate: sherwood oil=1:8, separates and obtains 7.0g compound 4a, yield 63%.
After testing, m.p.163-164 DEG C of .IR υ (cm
-1): 3054,3004,2946,2827,1601,1580,1484,1466,1411,1378,1305.
1h NMR (CDCl
3) δ: 1.79-1.87 (m, 2H), 2.13-2.17 (m, 2H), 2.77 (t; J=6.5Hz, 2H), 3.71 (s, 3H), 3.82 (s; 3H), 6.87-6.91 (m, 4H), 7.38-7.47 (m, 4H);
13c NMR (CDCl
3) δ: 18.93,24.12,32.86,55.87,57.28,101.03,108.77,111.43,111.99,113.02,119.62,124.75,127.28,129.78,134.17,148.04,150.87,153.68; ESI-MS (+) m/z:349[M+H]
+.
Adopt same procedure to obtain compound 4b, yield 27% taking 3b as raw material.
After testing, m.p.143-145 DEG C.
1H?NMR(CDCl
3),δ:1.90-1.96(m,2H),2.12-2.16(m,2H),2.84(t,J=6.0Hz,2H),3.89(s,3H),3.91(s,3H),6.67(s,1H),6.92-6.95(m,1H),7.29(d,J=6.0Hz,1H),7.41-7.51(m,4H);
13C?NMR(CDCl
3):δ:19.96,29.06,31.01,55.94,55.95,100.82,109.34,109.52,110.71,113.90,120.23,127.13,127.28,130.99,134.20,146.02,148.38,150.08;ESI-MS(+)m/z:349[M+H]
+。
Embodiment 5 spiral shell dinaphthyl target compounds 5,8-dimethoxy-2,3-naphthalene-Isosorbide-5-Nitrae-diketone Spiroketals (WM1)
with 6,7-dimethoxy-2,3-naphthalene-Isosorbide-5-Nitrae-diketone Spiroketals (WM2)
synthetic
In 100mL single port bottle, add 1.5g(4.3mmol) 4a, 4.5g dichromic acid pyridinium (PDC), 8.6g diatomite and 40mL benzene, under ice-water bath condition, in reaction system, slowly drip 3mL5-6mol/L peroxy tert-butyl alcohol (t-BuOOH) with syringe, about 15min dropwises the water-bath of recession deicing, under agitation condition, after room temperature reaction 24h, add 1mL5-6mol/Lt-BuOOH, stopped reaction after continuation reaction 24h, by decompress filter after ethyl acetate dilution for reaction solution, filtrate is used respectively to 1mol/L HCl and the each washed twice of water, then use anhydrous Na
2sO4 is dry, concentrates and crosses silicagel column and separate, ethyl acetate: sherwood oil=1:5 wash-out, reclaim raw material 4a0.12g, and separate to obtain 0.59g compound WM1, yield 38%.
After testing, m.p.174-176 DEG C.IRυ(cm
-1):3060,2964,2936,2837,1695,1606,1578,1479,1410,1378,1279,1154,1037;
1H?NMR(CDCl
3)δ:2.48-2.53(m,2H),2.72-2.77(m,2H),3.75(s,3H),3.91(s,3H),6.94(d,J=7.2Hz,2H),7.12(d,J=9.2Hz,1H),7.28(d,J=9.2Hz,1H),7.40-7.50(m,4H);
13C?NMR(75MHz,CDCl3)δ:31.37,36.90,56.91,57.88,99.98,109.02,112.74,115.57,120.26,121.59,122.76,127.41,129.50,134.25,147.38,152.72,153.43,196.07;ESI-MS(+)m/z:385.1[M+Na]
+。
Adopt same procedure to obtain compound WM2, yield 49% taking 4b as raw material.
After testing, m.p.143-145 DEG C.
1H?NMR(CDCl
3):δ:2.49-2.53(m,2H),2.77(t,J=6.9Hz,2H),3.99(s,3H),4.00(s,3H),6.99(dd,J=0.9Hz,7.4Hz,2H),7.41-7.59(m,6H);
13C?NMR(CDCl
3):δ:30.03,34.12,56.23,56.32,98.88,107.84,108.29,109.49,113.46,120.83,125.48,127.52,134.25,135.06,147.70,150.43,154.21;ESI-MS(+)m/z:385.1[M+Na]
+。
Embodiment 6 spiral shell dinaphthyl target compound 5-hydroxyl-8-methoxyl group-2,3-naphthalene-Isosorbide-5-Nitrae-diketone Spiroketals (WM3,8-methyl Palmarumycin CP
17)
synthetic
In 25mL single port bottle, by 60mg(0.2mmol) WM1 is dissolved in 10mLCHCl
3in, add 0.3mL Iodotrimethylsilane (CH
3)
3siI is in room temperature reaction 12h, and with reconcentration after a small amount of methyl alcohol dilution, resistates separates through silicagel column, ethyl acetate: sherwood oil=1:4 wash-out, separates and obtain compound WM342mg, yield 73%.
After testing, m.p.206-207 DEG C.IRυ(cm-1):3427,3062,2959,2920,2851,1693,1611,1588,1474,1409,1378,1295,1266,1057;
1H?NMR(CDCl3)δ:2.49-2.53(m,2H),2.67-2.71(m,2H),3.92(s,3H),7.06(dd,J=0.7Hz,7.5Hz,2H),7.13(d,J=9.2Hz,1H),7.24(d,J=9.4Hz,1H),7.47(t,J=8.4Hz,2H),7.59(dd,J=0.7Hz,8.4Hz,2H),7.64(s,1H);
13C?NMR(CDCl3)δ:29.46,35.60,56.98,102.45,110.50,113.59,116.93,121.50,121.77,123.67,124.81,127.57,134.18,146.34,148.92,153.71,194.94.HRMS:calcdfor?C
21H
17O
5,349.10705,found:[M+H]
+,349.10709。
Embodiment 7 spiral shell dinaphthyl target compounds 5,8-diacetoxy-2,3-naphthalene-Isosorbide-5-Nitrae-diketone Spiroketals (WM4)
with 5-acetoxyl group-8-methoxyl group-2,3-naphthalene-Isosorbide-5-Nitrae-diketone Spiroketals (WM5)
synthetic
1) spiral shell dinaphthyl intermediate 5,8-dihydroxyl-1-tetralone Spiroketals (5a) and 5-hydroxyl-8-methoxyl group-1-tetralone Spiroketals (5b) synthetic
In 250mL there-necked flask, add 1.0g(2.9mmol) 4a, 4.3mL(30.1mmol) Iodotrimethylsilane and 125mL CHCl
3, under 50 DEG C of conditions of oil bath heating, react stopped reaction after 72h, in system, add 10mL anhydrous methanol and stir 0.5h, then use 50mL CHCl
3by after reaction solution dilution, use respectively 5%Na
2s
2o
3after twice of solution and water washing, use again anhydrous Na
2sO
4dry, then, by the concentrated solvent rear silicagel column of crossing, elutriant is ethyl acetate: sherwood oil=1:5, crosses post and separates to obtain 0.79g compound 5a, yield 86%.
After testing, m.p.170-171 DEG C.IRυ(cm
-1):3057,2928,1610,1579,1466,1409,1388,1346.
1H?NMR(300MHz,CDCl
3)δ:1.87-1.94(m,2H),2.15-2.19(m,2H),2.77(t,J=3.1Hz,2H),4.44(s,1H),6.80(dd,J=8.7Hz,11.0Hz,2H),6.99(d,J＝0.9Hz,2H),7.02(s,1H),7.45(dd,J=7.5Hz,8.4Hz,2H),7.55(dd,J=0.8Hz,8.4Hz,2H);
13C?NMR(75MHz?CDCl3)δ:18.72,23.55,30.79,103.29,110.39,113.91,115.70,117.56,120.33,121.22,125.78,127.47,134.14,146.02,147.05,150.38。
In 250mL there-necked flask, add 1.7g(4.9mmol) 4a, 3.5mL(24mmol) Iodotrimethylsilane and 125mL CHCl
3, under 50 DEG C of conditions of oil bath heating, react stopped reaction after 72h, in system, add 10mL anhydrous methanol and stir 0.5h, then use 50mL CHCl
3by after reaction solution dilution, use respectively 5%Na
2s
2o
3after twice of solution and water washing, use anhydrous Na
2sO
4dry, then, by the concentrated solvent rear silicagel column of crossing, elutriant is ethyl acetate: sherwood oil=1:10, crosses post and separates to obtain 0.92g compound 5b, productive rate 58%.
After testing, m.p.164-166 DEG C of .IR υ (cm-1): 3440,3060,2998,2983,2944,2927,2864,2831,1606,1582,1477,1466,1410,1378,1263,1509;
1h NMR (CDCl3) δ: 1.83-1.89 (m, 2H), 2.13-2.17 (m, 2H), 2.78 (t; J=6.1Hz, 2H), 3.82 (s, 3H); 6.88 (dd, J=8.9Hz, 10.8Hz, 2H); 6.99 (dd, J=1.2,7.1Hz, 3H); 7.45 (dd, J=7.6,8.4Hz, 2H); 7.55 (dd, J=0.8,8.4Hz, 2H); HRMS:calcdfor C
21h
19o
4, 335.12779, found:[M+H]
+, 335.12778.
2) spiral shell dinaphthyl intermediate 5,8-diacetoxy-1-tetralone Spiroketals (6a) and 5-acetoxyl group-8-methoxyl group-1-tetralone Spiroketals (6b) synthetic
In 150mL flask, add 1.95g (6.1mmol) compound 5a, 1.8mL(12.9mmol) triethylamine and 50mL methylene dichloride, to under room temperature condition after bottle sealing, slowly inject 1.8mL(19.0mmol with syringe with the speed of 0.1mL/5min with moccasin plug) diacetyl oxide, after injection, continue after room temperature reaction 0.5h, react complete with TLC detection display raw material, there is new dot generation, stopped reaction, reaction solution was concentrated to silicagel column to be separated, using ethyl acetate: sherwood oil=1:6 is as eluent, separation obtains 1.65g compound 6a, yield 68%.
After testing, m.p.151-153 DEG C.IRυ(cm
-1):2943,2878,1763,1693,1640,1469,1375,1195;
1H?NMR(300MHz,CDCl
3)δ:1.75(s,3H),1.84-1.88(m,2H),2.14-2.18(m,2H),2.34(s,3H),2.69(t,J=12.2Hz,2H),6.92(dd,J=1.0Hz,7.2Hz,2H),7.04(d,J=8.7Hz,1H),7.17(d,J=8.7Hz,1H),7.40-7.51(m,4H);
13C?NMR(75MHz?CDCl
3)δ:18.62,20.59,20.74,24.15,31.92,100.10,109.14,112.68,120.28,123.25,123.56,127.44,128.17,133.09,134.17,145.98,147.28,147.70,168.74,169.61;HRMS:calcdfor?C
24H
21O
6,405.13326,found:[M+H]
+,405.13323。
Adopt same procedure to prepare compound 6b, yield 95% taking 5b as raw material.
After testing, m.p.148-150 DEG C.IRυ(cm
-1):3055,2952,2936,2837,1760,1603,1583,1477,1438,1413,1380,1276,1209,1065,1021;1HNMR(300MHz,CDCl
3)δ:1.56(s,3H),1.81-1.89(m,2H),2.12-2.16(m,2H),2.77(t,J=6.3Hz,2H),3.86(s,3H),6.90-6.93(m,3H),6.99(d,J=5.8Hz,1H),7.39-7.49(m,4H);
13C?NMR(75MHz,CDCl
3)δ:18.77,20.62,23.75,31.97,55.78,100.49,109.08,110.83,112.77,120.14,122.58,127.41,129.67,134.18,142.89,147.48,154.53,170.23；HRMS:calcdfor?C
23H
21O
5,377.13835,found:[M+H]
+,377.13840。
3) spiral shell dinaphthyl target compound 5,8-diacetoxy-2,3-naphthalene-Isosorbide-5-Nitrae-diketone Spiroketals (WM4) and 5-acetoxyl group-8-methoxyl group-2,3-naphthalene-Isosorbide-5-Nitrae-diketone Spiroketals (WM5) synthetic
In 50mL single port bottle, add 210mg(0.56mmol) 6b, 0.4g PDC, 1.2g diatomite and 6mL benzene, under ice-water bath condition, slowly drip 1mL5-6M t-BuOOH with syringe to it, about 15min dropwises the water-bath of recession deicing, under agitation condition, after room temperature reaction 24h, add 0.5mL5-6M t-BuOOH, stopped reaction after continuation reaction 24h, by decompress filter after ethyl acetate dilution for reaction solution, filtrate is used respectively to 1M HCl and the each washed twice of water, then use anhydrous magnesium sulfate drying, concentrate and cross post and separate; Fill out post, ethyl acetate with silica gel: sherwood oil=1:5 wash-out, separates to obtain 152mg compound WM5, yield 69%.
After testing, m.p.148-150 DEG C.IRυ(cm
-1):2925,2853,1748,1583,1478,1412,1379,1310,1276,1113;1H?NMR(CDCl3)δ:1.83(s,3H),2.48-2.52(m,2H),2.72-2.77(m,2H),3.97(s,3H),6.96(dd,J=1.0Hz,7.4Hz,2H),7.18(d,J=9.3Hz,1H),7.35(d,J=9.1Hz,1H),7.45(dd,J=7.4Hz,8.3Hz,2H),7.53(dd,J=1.0Hz,8.5Hz,2H);
13C?NMR(75MHz,CDCl
3)δ:20.51,30.50,36.40,56.71,99.41,109.33,112.49,114.70,120.78,122.24,127.54,131.30,132.59,134.19,141.78,146.76,157.28,169.92,194.86.HRMS:calcdfor?C
23H
19O
6,391.11761,found:[M+H]
+,391.11774。
Adopt same procedure to prepare compound WM4, yield 55% taking 6a as raw material.
After testing, m.p.136-137 DEG C.IRυ(cm
-1):2945,2859,1750,1585,1482,1408,1375,1304,1278,1115;
1H?NMR(CDCl3)δ:1.81(s,3H),2.28(s,3H),2.49-2.53(m,2H),2.71-2.77(m,2H),6.95(dd,J=1.0Hz,7.4Hz,2H),7.18(d,J=9.3Hz,1H),7.36(d,J=9.1Hz,1H),7.47(dd,J=7.4Hz,8.3Hz,2H),7.55(dd,J=1.0Hz,8.5Hz,2H);
13C?NMR(75MHz,CDCl
3)δ:20.50,21.81,30.61,36.52,99.52,109.43,112.51,114.68,120.76,122.25,127.54,131.35,132.64,134.22,141.83,146.79,157.26,169.95,194.88.HRMS:calcd?for?C
24H
19O
7,419.11308,found:[M+H]
+,419.11315。
Embodiment 8 spiral shell dinaphthyl target compounds 5,8-dihydroxy oxygen base-2,3-naphthalene-Isosorbide-5-Nitrae-diketone Spiroketals (WM6)
with 5-hydroxyl-8-methoxyl group-2,3-naphthalene-Isosorbide-5-Nitrae-diketone Spiroketals (WM3)
synthetic
In 25mL single port bottle, by 168mg(0.40mmol) WM4 is dissolved in 5mL methyl alcohol, under stirring at room temperature condition, add the sodium hydroxide solution of 9mL1% to it, room temperature reaction 30min, with the conversion completely of TLC monitoring demonstration raw material, stopped reaction, regulate pH with 1MHCl, there are a large amount of Precipitations therebetween, in the time that pH regulator is 5-6, stop dripping HCl, after being spin-dried for, methyl alcohol in system adds ethyl acetate extraction, collect organic phase and with anhydrous magnesium sulfate drying, dried organic phase is spin-dried for to obtain to 122mg compound WM6, yield 91%.
After testing, m.p.173-174 DEG C.IRυ(cm
-1):3435,3064,2969,2924,2856,1695,1610,1585,1473,1407,1376,1290,1264,1058;
1H?NMR(CDCl
3)δ:2.49-2.53(m,2H),2.74-2.78(m,2H),7.04-7.07(m,3H),7.24-7.27(m,1H),7.48(t,J=7.4Hz,2H),7.59(d,J=7.5Hz,2H),7.65(s,1H),12.36(s,1H);
13C?NMR(CDCl
3)δ:28.98,33.85,102.06,110.46,113.53,114.49,119.49,121.85,127.61,128.87,134.22,146.29,147.68,157.20,202.41.HRMS:calcd?for?C
21H
17O
5,333.07685,found:[M-H]
-,333.07689。
Adopt same procedure to prepare compound WM3, yield 93% taking WM5 as raw material.Its m.p., IR,
1h NMR and
13c NMR is shown in example 6.
The preparation of embodiment 9 compound WM series solution
The preparation of compound WM series and control sample mother liquor: take respectively new compound (WM1, WM3, WM5,4a, 5a, 5b, 6a, 6b), the each 25 ± 1mg of m-tetrachlorophthalodinitrile with ten thousand/electronic balance, dissolve with 5mL DMSO the mother liquor that is prepared into 5000 μ g/mL respectively.
The setting of concentration: under aseptic technique, the 5000 μ g/mL that prepare for mother liquor potato dextrose agar (PDA substratum) be diluted to the toxic culture medium flat plate of 50 μ g/mL, the not blank containing chemicals treatment is established in test, and each processing repeated 3 times.The toxic culture medium flat plate that the good inhibiting rate of activity is greater than 70% compound resampling PDA substratum and is diluted to five different concns, carries out further accurate toxicity test.
The biological activity determination of embodiment 10WM series compound
This test, according to People's Republic of China's agricultural industry criteria (NY/T1156.2-2006), adopts mycelial growth rate method to measure.By cultured various pathogenic bacterias, under aseptic technique, with the sterilizing punch tool of diameter 5mm, cut bacterium cake from colony edge, with inoculator, pure culture biscuits involvng inoculation is dull and stereotyped central in pastille, mycelia faces down, and covers ware lid, is placed in 25 DEG C of incubators and cultivates.
According to the growing state investigation pathogenic bacteria mycelial growth situation of bacterium colony in blank culture dish, after the bacterium colony in blank is fully grown, measure the colony diameter of each processing with right-angled intersection method, adopt formula below to calculate bacterium colony growth diameter, get its mean value.Measurement result is calculated by following method, and the bacterium colony that increases diameter and chemicals treatment with blank bacterium colony increases diameter and calculates the mycelial growth inhibition rate of each chemicals treatment to various pathogenic bacterias, the results are shown in Table 1.
Table 1 compound WM1, WM3, WM5 and intermediate 4a, 5a, 5b, 6a, 6b
Fungicidal activity primary dcreening operation (inhibiting rate, %) to phytopathogen
The result demonstration of table 1, it is active that all compounds demonstrate good inhibition to botrytis cinerea, but to cotton-wilt fusarium, asparagus stem is withered, and the inhibition activity of fusarium graminearum and peanut Cercospora bacteria is poor.Compound WM5 is 71.3% to the inhibiting rate of rice wilt pathogens, and compound WM1 and 5b are respectively 73.7% and 75.0% to the inhibiting rate of Botryosphaeria berengeriana f. sp.
2 compound WM1, the multiple sieve result of 5b to Botryosphaeria berengeriana f. sp
Table 4 compound WM1,5b, WM5 sieve result and EC50 value again
The presentation of results of table 2, table 3, table 4, compound WM1 and 5b have good inhibition activity to Botryosphaeria berengeriana f. sp, and compound WM5 has showed good inhibition activity to rice wilt pathogens.
Although above the present invention is described in detail with a general description of the specific embodiments, on basis of the present invention, can make some modifications or improvements it, this will be apparent to those skilled in the art.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, all belong to the scope of protection of present invention.
Reference:
1.Martinez-Luis?S,Della-Togna?G,Coley?P,Kursar?T,Gerwick?W,Cubilla-Rios?L.Antileishmanial?constituents?of?the?Panamanian?Endophytic?fungus?Edenia?sp.J.?Nat.Prod.,2008,71:2011-2014。
2.Martinez-Luis?S,Della-Togna?G,Coley?P,Kursar?T,Gerwick?W,Cubilla-Rios?L.Additional?anti-leishmanial?constituents?of?the?panamanian?endophytic?fungus?Edenia?sp.Revista?Latinoamericana?de?Quimica.2009,37:104-114。
3. Zhou Ligang, Peng Youliang, Jiang Weibo, Wang Mingan, Zhao Wensheng, Cai Xiaoyue, Huang Yongfu, Xu Lijian.The preparation of peltate yam endophytic fungi spiro-dinaphthyl compound and as the application of sterilant, CN101525578,2009.
4.Cai?Xiaoyue,Shan?Tijiang,Li?Peiqin,Huang?Yongfu,Xu?Lijian,Zhou?Ligang,Wang?Mingan,Jiang?Weibo.Spirobisnaphthalenes?from?the?endophytic?fungus?Dzf12?of?Dioscorea?zingiberensis?and?their?antimicrobial?activities.Nat.Prod.?Commun.,2009,4:1469-1472。
5.Wipf?P，Jung?JK,Rodriguez?S,Lazo?JS.Synthesis?and?biological?evaluation?of?deoxypreussomerin?A?and?palmarumycin?CP1?and?related?naphthoquinone?spiroketals.Tetrahedron,2001,57:283-296。
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8.Aslan?A,Altun?S,Ahmed?I,Florke?U,Schulz?B,Krohn?k.Synthesis?of?biologically?active?nonnatural?Palmarumycin?derivatives.Eur?J.?Org.Chem.,2011,1176-1188。
Claims (5)
1. a spiro-dinaphthyl compound, is characterized in that, is selected from following structural compounds:
,
,
.
2. compound according to claim 1, is characterized in that, is selected from following structural compounds:
,
.
3. the method for the spiro-dinaphthyl compound described in preparation claim 1 or 2, is characterized in that, comprises the steps:
1)
with Succinic anhydried at anhydrous AlCl
3the lower reaction of effect, generates
;
2)
under alkaline condition, oil bath heating generates with hydrazine hydrate
;
3)
cyclization reagent PPA reacts with pass, generates
;
4)
with pyridine tosilate, 1, the reaction of 8-dihydroxy naphthlene generates
;
5)
obtain the spiro-dinaphthyl compound described in claim 1 or 2 through oxidizing reaction;
In described step 5)
under the effect of dichromic acid pyridinium, carry out oxidizing reaction with peroxy tert-butyl alcohol, generate
;
Described
demethylation obtains compound
;
When
while being 5,8-dimethoxy-1-tetralone Spiroketals with (CH
3)
3siI in molar ratio 1:5 ~ 6 hybrid reaction, again through the oxidation of phenolic hydroxyl group esterification, benzyl position, generate
;
Described
under alkaline condition, hydrolysis generates
.
4. the method for spiro-dinaphthyl compound according to claim 3, is characterized in that, described step 1) is under ice-water bath condition, to add anhydrous AlCl in batches
3;
Described step 2) be that reaction refluxes 4 ~ 5 hours under 135 ~ 145 DEG C of conditions, continue to be warming up to 200 ~ 220 DEG C to steam except unnecessary hydrazine hydrate, then be down to 190 ~ 200 DEG C of reactions 4 ~ 5 hours; Described hydrazine hydrate concentration is 85%;
Described step 3) is to react 0.5 ~ 1 hour under 70 ~ 80 DEG C of conditions.
5. the spiro-dinaphthyl compound described in claim 1 or 2 is in the application of preparing in disinfectant use in agriculture.
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|---|---|---|---|---|
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|---|---|---|---|---|
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Non-Patent Citations (6)
| Title |
|---|
| 12-N-Methylated 5,6-dihydrobenzo[c]acridine derivatives: A new class of highly selective ligands for c-myc G-quadruplex DNA;Sheng-Rong Liao, et al.;《European Journal of Medicinal Chemistry》;20120330;第53卷;52-63 * |
| A NOVEL ROUTE TO 1,8-DIHYDROXYNAPHTHALENE-DERIVED NATURAL PRODUCTS. SYNTHESIS OF (±)-CJ-12,372;Masayuki Inoue, et al.,;《HETEROCYCLES》;20020729;第59卷(第1期);87-92 * |
| AnthonyG.M.Barrett et al..Total syntheses of palmarumycins CP1 and CP2 and CJ-12 |
| Masayuki Inoue, et al.,.A NOVEL ROUTE TO 1,8-DIHYDROXYNAPHTHALENE-DERIVED NATURAL PRODUCTS. SYNTHESIS OF (±)-CJ-12,372.《HETEROCYCLES》.2002,第59卷(第1期),87-92. |
| Sheng-RongLiao et al..12-N-Methylated 5 |
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