CN101812046A - 1,4-oxa-compound, furan compound, synthetic method and applications - Google Patents
1,4-oxa-compound, furan compound, synthetic method and applications Download PDFInfo
- Publication number
- CN101812046A CN101812046A CN 201010114566 CN201010114566A CN101812046A CN 101812046 A CN101812046 A CN 101812046A CN 201010114566 CN201010114566 CN 201010114566 CN 201010114566 A CN201010114566 A CN 201010114566A CN 101812046 A CN101812046 A CN 101812046A
- Authority
- CN
- China
- Prior art keywords
- compound
- oxa
- plain
- reaction
- furan
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention relates to a chiral 1,4-oxa-compound and a furan compound which are synthesized in high efficiency and high enantioselectivity by an intramolecular oxa-Michael reaction of cyclohexadienone derivatives catalyzed by chiral phosphoric acid. The furan compound can be used for preparing a clerodendrum indicum extract natural product. The method has mild reaction conditions and simple operation. In addition, any metal salt compound is not added during the reaction, which is beneficial to producing and treating potential biological active compounds. The method has good reaction yield (71% to 93% generally) and high enantioselectivity (61% to >99% generally).
Description
Technical field
The present invention relates to a kind of chirality 1,4-oxa-compound and furan compound, system carries out intramolecularly oxa-Michael reaction high-level efficiency, high enantioselectivity ground synthesis of chiral 1 by the acid catalyzed cyclohexadiene ketone derivatives of chiral phosphorus, 4-oxa-compound and furan compound, this furan compound can be used to prepare the plain class natural product of Herba Clerodendri Indici.
Background technology
In recent years, organic molecule catalysis has caused extensive concern [(a) Seayad, the J. of academia and industry member in worldwide owing to advantages such as it are easily synthetic, and structural modification is convenient, and heavy metal free is residual; List, B.Org.Biomol.Chem.2005,3,719-724. (b) Dalko, P.I.; Moisan, L.Angew.Chem.Int.Ed.2004,43,5138-5175.], wherein the asymmetry catalysis of being realized as catalyzer by chirality phosphoric acid has been obtained development [(a) Akiyama, T. rapidly in recent years especially; Itoh, J.; Yokota, K.; Fuchibe, K.Angew.Chem.Int.Ed.2004,43,1566-1568. (b) Uraguchi, D.; Terada, M.J.Am.Chem.Soc.2004,126,5356-5357. (c) Uraguchi, D.; Sorimachi, K.; Terada, M.J.Am.Chem.Soc.2004,126,11804-11805.].In this field, we have developed the intramolecularly oxa-Michael reaction by the acid catalyzed cyclohexadiene ketone derivatives of chiral phosphorus, this reaction can high-level efficiency, the synthesis of chiral ring-type oxa-compound of high enantioselectivity, as 1, and 4-oxa-compound and furan compound.The oxa-ring compound is present in [(a) Tang, Y. in the natural product and drug molecule of a large amount of biologically actives; Oppenheimer, J.; Song, Z.-L.; You, L.-F.; Zhang, X.-J.; Hsung, R.P.Tetrahedron 2006,62,10785. (b) Shi, Y.-L.Shi, M.Org.Biomol.Chem.2007,5,1499.], but, hindered development [Nising, the C.F. of its asymmetric methodology aspect because often there is certain reversibility in oxa-Michael reaction;
S., Chem.Rev.2008,37,1218.].Thereby develop a kind of easy to operately, particularly the asymmetric oxa-Michael of high-level efficiency, high enantioselectivity reaction is the emphasis and the difficult point of this respect.Our this organic micromolecule catalyst of development utilization chirality phosphoric acid, oxa-Michael reaction in the catalytic molecular in several minutes to a few hours, as 1,4-oxa-compound and furan compound have great significance to synthesis of chiral oxa-ring compound.In addition, oxa-Michael product such as furan compound can synthesize the Herba Clerodendri Indici chlorins compound simply efficiently by further transforming, and this compounds can extract acquisition from the plant Herba Clerodendri Indici, this plant usually is used for treating malaria and rheumatosis [(a) Tian, J. in China; Zhao, Q.-S.; Zhang, H.-J.; Lin, Z.-W.; Sun, H.-D.J.Nat.Prod.1997,60,766. (b) Cheng, H.-H.; Wang, H.-K.; Ito, J.; Bastow, K.F.T.Y.; Nakanishi, Y.; Xu, Z.; Luo, T.-Y.; Lee, K.-H.J.Nat.Prod.2001,64,915.].But have only a spot of report, and step cumbersome [(a) Honzumi, M. about the asymmetric synthesis of Herba Clerodendri Indici chlorins compound; Kamikubo, T.; Ogasawara, K.Synlett 1998,1001. (b) Canto, M.; DeMarch, P.; Figueredo, M.; Font, J.; Rodriguez, S.; Alarez-Larena, A.; Piniella, J.F.Tetrahedron:Asymmetry 2002,13,455. (c) You, Z.; Hoveyda, A.H.; Snapper, M.L.Angew.Chem.Int.Ed.2009,48,547. (d) Wenderski, T.A.; Huang, S.-L.; Pettus, T.R.R.J.Org.Chem.2009,74,4104.].We apply to this methodology in synthesizing of these natural products, have synthesized simply efficiently to have the plain class compounds of optically active Herba Clerodendri Indici.
Summary of the invention
The purpose of this invention is to provide and a kind ofly contain 1,4-oxa-compound and furan compound;
Purpose of the present invention or provide a kind of effectively synthetic above-mentioned 1, the method for 4-oxa-compound and furan compound;
Another object of the present invention provides a kind of asymmetric synthesis Herba Clerodendri Indici chlorins compound method.
Method of the present invention a kind of 1,4-oxa-compound and furan compound have following structural formula:
R wherein
1Be selected from H arbitrarily, the alkyl of C1-C16; R wherein
2Be selected from OH, OOH, C arbitrarily
3-C
16Cycloalkyl, C
4-C
10The aryl that replaces of the heterocyclic radical that contains N, O or S, aryl, R; Described aryl is a phenyl or naphthyl; R is C
1-C
4Alkyl, C
1-C
4Perfluoroalkyl, halogen or C
1-C
4Alkoxyl group; Wherein X is selected from CH arbitrarily
2Or OCH
2
Of the present inventionly a kind ofly contain 1,4-oxa-compound and furan compound are to be raw material with the cyclohexadiene ketone derivatives, in the presence of organic solvent, are that catalyst reaction makes with chirality phosphoric acid, and available following reaction formula is represented:
The further description of this reaction is to be-78 ℃ to 100 ℃ at the organic solvent neutral temperature, the cyclohexadiene ketone derivatives is a raw material, with chirality phosphoric acid is catalyst reaction 5 minutes-48 hours, the mol ratio of described cyclohexadiene ketone derivatives and chirality phosphoric acid is 1: 0.01-0.5, the mol ratio of recommendation response is: the cyclohexadiene ketone derivatives: chirality phosphoric acid=1: 0.05-0.2. recommendation response temperature is :-60 ℃ to 25 ℃.The general structure of catalyzer is (be any optically pure structure, not limit by diagram):
R wherein
8, R
9, R
10,
R
11, R
12The aryl that alkyl, the triphenyl that is selected from H, C1-C16 arbitrarily is silica-based, aryl, R replace; Described aryl is phenyl, naphthyl, anthryl or phenanthryl; R is C
1-C
4Alkyl, C
1-C
4Perfluoroalkyl, halogen or C
1-C
4Alkoxyl group.
In the inventive method, described water is distilled water.Described organic solvent can be polarity or non-polar solvent, as benzene, tetracol phenixin, sherwood oil, tetrahydrofuran (THF), dimethyl formamide, ether, methylene dichloride, trichloromethane, toluene, dimethylbenzene, hexanaphthene, normal hexane, normal heptane, dioxane or acetonitrile etc.
Adopt the inventive method products therefrom can pass through recrystallization, thin-layer chromatography, the in addition separation and purification of methods such as column chromatography underpressure distillation.As the method with recrystallization, recommending solvent is the mixed solvent of polar solvent and non-polar solvent.Recommend solvent to can be methylene dichloride---normal hexane, Virahol---sherwood oil, ethyl acetate---sherwood oil, ethyl acetate---normal hexane, Virahol---ethyl acetate---mixed solvents such as sherwood oil.With thin-layer chromatography and column chromatography method, used developping agent is the mixed solvent of polar solvent and non-polar solvent.Recommend solvent to can be Virahol---sherwood oil, ethyl acetate---sherwood oil, ethyl acetate---normal hexane, Virahol---ethyl acetate---mixed solvents such as sherwood oil, its volume ratio can be respectively: polar solvent: non-polar solvent=1: 0.1-500. for example: ethyl acetate: sherwood oil=1: 0.1-50, Virahol: sherwood oil=1: 0.1-500.
Furan compound of the present invention can be used to prepare the Herba Clerodendri Indici chlorins compound, and its structural formula is as follows:
The plain F of Herba Clerodendri Indici, the plain C of Herba Clerodendri Indici or the plain D of Herba Clerodendri Indici.
It is as follows further to specifically describe method of the present invention: in organic solvent and under the room temperature, foregoing furan compound of the present invention and reductive agent reaction obtained the plain F compound of Herba Clerodendri Indici in 1-72 hour, and the mol ratio of described furan compound and reductive agent is 1: 1-5; Described reductive agent is S-WAT, Sulfothiorine, triphenyl phosphite or triphenyl phosphorus.
In organic solvent and under the room temperature, the plain F compound of aforesaid Herba Clerodendri Indici obtained the plain C compound of Herba Clerodendri Indici in 1-72 hour in the reaction of palladium hydrocarbonize, plain F compound of described Herba Clerodendri Indici and palladium carbon 1: 0.01-0.2.
In organic solvent and under the room temperature, foregoing furan compound and salt of wormwood, yellow soda ash or benzyltrimethylammonium hydroxide reacted 1-72 hour, followed and the plain D compound of reductive agent reaction acquisition in 1-72 hour Herba Clerodendri Indici; Described reductive agent is triethyl-boron aluminum hydride, aluminium amalgam or Lithium Aluminium Hydride; The mol ratio of described furan compound and salt of wormwood, yellow soda ash or benzyltrimethylammonium hydroxide is 1: 0.1-0.5; The mol ratio of described furan compound and reductive agent is 1: 1-10.
The invention provides a kind of effectively by chirality phosphoric acid as catalyzer, be the synthesis of chiral oxa-ring compound of raw material high-level efficiency, high enantioselectivity by the cyclohexadiene ketone derivatives, as 1, the method for 4-oxa-compound and furan compound; Wherein the furans product can efficient production Herba Clerodendri Indici chlorins compound through simple conversion.This synthetic method catalyzer is easy to get relatively, catalytic activity height, wide application range of substrates, product enantioselectivity height, and the reaction conditions gentleness is easy and simple to handle.In addition, need not in the reaction to add any metal salt compound, thereby help medicine production and processing.And the productive rate of reaction is better (being generally 71%-93%) also, enantioselectivity height (being generally 61%-99%).
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1: the preparation of chirality phosphoric acid
Under the room temperature argon shield, the derivative (0.5mmol) with BINOL in an exsiccant reaction tubes is dissolved in the 1mL exsiccant pyridine, under quick stirring condition, the phosphorus oxychloride of (1.0mmol) is added drop-wise in the system stirring at room 3 hours slowly.1mL water is added drop-wise in the system slowly, again stirring at room 30 minutes.Add the methylene dichloride dissolving, (decompression is revolved and is desolvated for 3 * 10mL) washings, organic layer anhydrous sodium sulfate drying, and the residue column chromatography for separation gets product with the 1N aqueous hydrochloric acid.
(S)-3,3 '-[3,5-two (trifluoromethyl) phenyl] 2-1,1 '-binaphthol phosphoric acid
(S)-3，3′-[3，5-Bis(trifluoromethyl)phenyl]2-1，1′-binaphthyl?phosphate
Solid, 89% productive rate (yield) .IR (CHCl
3) 1620,1501,1474,1379,1325,1281,1246,1178,1140,1109,1084,1024,988,964,891,870,867cm
-1.
1H NMR (400MHz, CDCl3) δ=8.01 (s, 8H), 7.61-7.58 (m, 4H), 7.42-7.39 (m, 4H).
31P NMR (189MHz, CDCl
3) δ=4.61.
13C NMR (100MHz, CDCl
3) δ=143.5 (d, J
P-C=9.3Hz), 138.6,132.3,132.0,131.4,131.4 (q, J
C-F=33.4Hz), 131.1 (d, J
P-C=3.1Hz), 129.9,128.7,127.6,127.1,126.8,123.1 (q, J
C-F=272.9Hz), 122.5 (d, J
P-C=1.9Hz), 121.5.
19F NMR (376MHz, CDCl
3) δ=96.3.
Embodiment 2: the acid catalyzed intramolecularly oxa-of chiral phosphorus Michael reaction
Under the argon shield, in an exsiccant reaction tubes, add cyclohexadiene ketone derivatives (0.3mmol), and the chiral phosphorus acid catalyst (22.8mg, 10mol%), activatory
Molecular sieve (150mg) and methylene dichloride (6mL).React under the room temperature to raw material disappearance (TLC detection).Reaction solution is through diatomite filtration, and solid washed with dichloromethane, filtrate decompression are revolved and desolvated, residue through plate layer chromatography separate product.
P1:(4aS, 8aR)-8a-methyl-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P1：(4aS，8aR)-8a-methyl-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
White solid, 91%yield, 94%ee[62%yield, 99%ee (ethyl acetate/petroleum ether, recrystallization)] .Analytical data for P1 (99%ee): [α]
D 20=+23.6 ° of (c=0.5, CHCl
3) .Mp=105-106 ℃.
1H NMR (300MHz, CDCl
3) δ 1.39 (s, 3H), 2.59 (dd, J=3.0,17.4Hz, 1H), 2.69 (dd, J=3.0,17.1Hz, 1H), and 3.63-3.73 (m, 3H), 3.80-3.83 (m, 1H), 3.89-3.91 (m, 1H), 6.11 (d, J=10.5Hz, 1H), 6.70 (dd, J=3.0,10.5Hz, 1H);
13C NMR (75MHz, CDCl
3) δ 24.5,42.0,62.9,66.2,71.9,78.2,130.5,152.3,195.7; IR (KBr) 2977,2914,2863,1674,1414,1386,1350,1287,1233,1124,1097,1023,953,946,791,697cm
-1HRMS (EI): high resolution mass spectrum calculating value C
9H
12O
3: 168.0786. measured value: 168.0786. chirality test condition: Daicel Chiralpak OB-H (25cm), normal hexane/Virahol=90/10,0.6mL/min
-1, λ=220nm, t
R(major)=and 22.04min, t
R(minor)=26.49min.
P2:(4aS, 8aR)-8a-ethyl-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P2：(4aS，8aR)-8a-ethyl-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
Semisolid, 91%yield, 78%ee.Analytical data for P2:[α]
D 20=+27.7 ° of (c=1.0, CHCl
3).
1H NMR (400MHz, CDCl
3) δ 1.04 (t, J=7.2Hz, 3H), 1.71-1.75 (m, 2H); 2.55-2.71 (m, 2H), 3.67-3.70 (m, 3H), 3.79-3.86 (m, 1H), 3.93-3.95 (m, 1H), 6.13 (dd, J=1.2,10.4Hz, 1H), 6.73 (dd, J=2.8,10.4Hz, 1H);
13C NMR (100MHz, CDCl
3) δ 7.2,31.4,41.8,62.8,66.2,73.8,76.9,130.9,152.3,195.8; IR (KBr) 2973,2920,2866,1686,1411,1382,1275,1126,1096,992,966,926,793,697cm
-1HRMS (EI): high resolution mass spectrum calculating value C
10H
14O
3: 182.0943. measured value: 182.0941 chirality test conditions: DaicelChiralpak OB-H (25cm), normal hexane/Virahol=90/10,0.6mL/min
-1, λ=220nm, t
R(major)=and 22.21min, t
R(minor)=26.78min.
P3:(4aS, 8aR)-8a-sec.-propyl-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P3:(4aS, 8aR)-8a-isopropyl-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
Faint yellow solid, 71%yield, 61%ee.Analytical data for P3:[α]
D 20=+1.6 ° of (c=0.6, CHCl
3) .Mp=65-67 ℃.
1H NMR (300MHz, CDCl
3) δ 1.03 (d, J=6.9Hz, 3H), 1.08 (d, J=6.9Hz, 3H), 1.95 (heptet, J=6.9Hz, 1H), and 2.52-2.73 (m, 2H), 3.64-3.71 (m, 3H), and 3.80-3.88 (m, 1H), 4.13-4.16 (m, 1H), 6.14 (d, J=10.5Hz, 1H), 6.82 (d, J=10.5Hz, 1H);
13C NMR (75MHz, CDCl
3) δ 16.8,17.2,35.6,41.3,62.6,66.2,75.0,75.5,130.6,153.8,195.8; IR (KBr) 2957,2918,2860,1683,1379,1279,1261,1222,1137,1101,998,922,802,774,690cm
-1HRMS (EI): high resolution mass spectrum calculating value C
11H
16O
3: 196.1099. measured value: 196.1097. chirality test condition: Daicel Chiralpak OB-H (25cm), normal hexane/Virahol=90/10,0.6mL/min
-1, λ=220nm, t
R(major)=and 18.93min, t
R(minor)=21.81min.
P4:(4aS, 8aS)-8a-phenyl-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P4：(4aS，8aS)-8a-phenyl-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
White solid, 92%yield, 91%ee[68%yield, 99%ee (ethyl acetate/petroleum ether, recrystallization)] .Analytical data for P4 (99%ee): [α]
D 20=+171.6 ° of (c=0.39, CHCl
3) .Mp=123-124 ℃.
1H NMR (300MHz, CDCl
3) δ 2.45 (d, J=3.0Hz, 2H), 3.84-3.91 (m, 3H), 4.03-4.07 (m, 2H), 6.48 (d, J=10.5Hz, 1H), 6.78 (dd, J=3.0,10.5Hz, 1H), 7.35-7.43 (m, 3H), 7.54-7.57 (m, 2H);
13C NMR (75MHz, CDCl
3) δ 41.2,62.8,66.3,76.9,79.3,126.7,128.6,128.7,132.9,138.4,148.7,196.4; IR (KBr) 2968,2916,2868,1685,1490,1446,1401,1263,1218,1120,1087,979,917,777,758,696cm
-1HRMS (EI): high resolution mass spectrum calculating value C
14H
14O
3: 230.0943. measured value: 230.0942. chirality test condition: Daicel ChiralpakAS-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 22.44min, t
R(minor)=34.19min.
P5:(4aS, 8aS)-8a-(4-fluorophenyl)-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P5：(4aS，8aS)-8a-(4-fluorophenyl)-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
White solid, 91%yield, 90%ee.Analytical data for P5:[α]
D 20=+137.1 ° of (c=0.5, CHCl
3) .Mp=159-160 ℃.
1H NMR (300MHz, CDCl
3) δ 2.53-2.37 (m, 2H), 3.84-3.89 (m, 3H), 3.99-4.10 (m, 2H), 6.48 (d, J=10.5Hz, 1H), 6.76 (dd, J=3.0,10.5Hz, 1H), 7.05-7.11 (m, 2H), 7.51-7.56 (m, 2H);
13C NMR (75MHz, CDCl
3) δ 41.1,62.9,66.3,76.5,79.3,115.5 (d, J=21.3Hz), 128.6 (d, J=8.2Hz), 133.1,134.3 (d, J=3.3Hz), 148.3,162.7 (d, J=246.6Hz), 196.15;
19F NMR (282MHz, CDCl
3) δ-113.42; IR (KBr) 3072,2970,2914,2865,1685,1604,1509,1491,1225,1161,1120,1102,1037,980,920,841,771,689cm
-1HRMS (EI): high resolution mass spectrum calculating value C
14H
13O
3F:248.0849. measured value: 248.0846. chirality test condition: Daicel Chiralpak AS-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 72.04min, t
R(minor)=102.38min.
P6:(4aS, 8aS)-8a-(4-chloro-phenyl-)-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P6：(4aS，8aS)-8a-(4-chlorophenyl)-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
White solid, 90%yield, 91%ee.Analytical data for P6:[α]
D 20=+162.7 ° of (c=0.4, CHCl
3) .Mp=135-136 ℃.
1H NMR (300MHz, CDCl
3) δ 2.37-2.47 (m, 2H), 3.84-3.89 (m, 3H), 3.96-4.07 (m, 2H), 6.48 (d, J=10.5Hz, 1H), 6.75 (dd, J=2.7,10.5Hz, 1H), 7.37 (d, J=8.7Hz, 2H), 7.49 (d, J=8.7Hz, 2H);
13C NMR (75MHz, CDCl
3) δ 41.1,62.8,66.3,76.6,79.2,128.2,128.8,133.2,134.8,137.1,148.1,196.1; IR (KBr) 2966,2916,2863,1692,1486,1402,1283,1262,1123,1094,1014,977,923,826,728; HRMS (EI): high resolution mass spectrum calculating value C
14H
13O
3Cl:264.0553. measured value: 264.0558. chirality test condition: Daicel Chiralpak AS-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 81.40min, t
R(minor)=105.82min.
P7:(4aS, 8aS)-8a-(4-bromophenyl)-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P7：(4aS，8aS)-8a-(4-bromophenyl)-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
White solid, 84%yield, 90%ee[64%yield, 99%ee (ethyl acetate/petroleum ether, recrystallization] .Analytical data for P7 (99%ee): [α]
D 20=+187.0 ° of (c=0.5, CHCl
3) .Mp=146-147 ℃.
1H NMR (300MHz, CDCl
3) δ 2.37-2.53 (m, 2H), 3,84-3.87 (m, 3H), 4.09-4.93 (m, 2H), 6.49 (d, J=10.5Hz, 1H), 6.74 (dd, J=3.0,10.5Hz, 1H), 7.42 (d, J=8.4Hz, 2H), 7.52 (d, J=8.4Hz, 2H);
13C NMR (75MHz, CDCl
3) δ 41.1,62.8,66.3,76.5,79.1,122.9,128.5,131.7,133.2,137.6,148.0,196.0; IR (KBr) 2916,2864,1695,1481,1398,1284,1263,1124,1115,1033,1002,977,824,677cm
-1HRMS (EI): high resolution mass spectrum calculating value C
14H
13O
3Br:308.0048. measured value: 308.0045. chirality test condition: Daicel Chiralpak AS-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 71.23min, t
R(minor)=98.27min.
P8:(4aS, 8aS)-8a-(4-aminomethyl phenyl)-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P8：(4aS，8aS)-8a-p-tolyl-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
White solid, 91%yield, 92%ee[72%yield, 99%ee (ethyl acetate/petroleum ether, recrystallization)] .Analytical data for P8 (99%ee): [α]
D 20=+212.6 ° of (c=1.1, CHCl
3) .Mp=164-165 ℃.
1H NMR (300MHz, CDCl
3) δ 2.36 (s, 3H), 2.45 (d, J=3.0Hz, 2H), 3.83-3.90 (m, 3H), 4.00-4.05 (m, 2H), 6.47 (d, J=10.5Hz, 1H), 6.77 (dd, J=2.7,10.5Hz, 1H), 7.20 (d, J=8.4Hz, 2H), 7.42 (d, J=8.4Hz, 2H);
13C NMR (75MHz, CDCl
3) δ 21.0,41.3,62.8,66.4,76.8,79.4,126.6,129.3,132.8,135.5,138.6,148.9,196.6; IR (KBr) 2974,2916,2864,1681,1517,1447,1404,1263,1106,1083,978,921,821,687cm
-1HRMS (EI): high resolution mass spectrum calculating value C
15H
16O
3: 244.1099. measured value: 244.1102; Chirality test condition: Daicel Chiralpak AS-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 24.12min, t
R(minor)=36.27min.
P9:(4aS, 8aS)-8a--(3-aminomethyl phenyl)-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P9：(4aS，8aS)-8a-m-tolyl-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
White solid, 91%yield, 91%ee[75%yield, 96%ee (ethyl acetate/petroleum ether, recrystallization)] .Analytical data for P9 (96%ee): [α]
D 20=+155.5 ° of (c=1.1, CHCl
3) .Mp=113-114 ℃.
1H NMR (300MHz, CDCl
3) δ 2.37 (s, 3H), 2.46 (d, J=3.0Hz, 2H), 3.83-3.91 (m, 3H), 4.01-4.06 (m, 2H), 6.48 (d, J=10.5Hz, 1H), 6.77 (dd, J=3.0,10.5Hz, 1H), 7.16 (d, J=6.9Hz, 1H), 7.25-7.37 (m, 3H); );
13C NMR (75MHz, CDCl
3) δ 21.5,41.3,62.8,66.3,76.9,79.3,123.8,127.3,128.4,129.5,132.8,138.3,138.4,148.9,196.6cm
-1IR (KBr) 2958,2921,2866,1689,1608,1404,1206,1121,1111,1002,791,706,691,661; HRMS (EI): high resolution mass spectrum calculating value C
15H
16O
3: 244.1099. measured value: 244.1101; Chirality test condition: Daicel Chiralpak AS-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 12.22min, t
R(minor)=19.61min.
P10:(4aS, 8aS)-8a-(2-aminomethyl phenyl)-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P10：(4aS，8aS)-8a-o-tolyl-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
White solid, 92%yield, 95%ee.Analytical data for P10:[α]
D 20=+66.6 ° of (c=1.0, CHCl
3) .Mp=107-108 ℃.
1H NMR (300MHz, CDCl
3) δ 2.34-2.52 (m, 2H), 2.75 (s, 3H), 3.79-3.88 (m, 2H), 3.97-4.06 (m, 2H), 4.49-4.51 (m, 1H), 6.49 (d, J=10.2Hz, 1H), 6.79 (dd, J=3.0,10.2Hz, 1H), 7.12-7.15 (m, 1H), 7.24-7.32 (m, 3H);
13C NMR (75MHz, CDCl
3) δ 22.8,41.6,62.4,65.6,75.0,78.5,125.70,128.0,128.8,132.7,133.8,135.3,137.8,149.7,196.7; IR (KBr) 2858,1690,1447,1402,1280,1263,1208,1109,1086,1001,977,921,752,725,687cm
-1HRMS (EI): high resolution mass spectrum calculating value C
15H
16O
3: 244.1099. measured value: 244.1102. chirality test condition: Daicel ChiralpakAS-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 19.98min, t
R(minor)=31.44min.
P11:(4aS, 8aS)-8a-(3, the 5-3,5-dimethylphenyl)-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P11：(4aS，8aS)-8a-(3，5-dimethylphenyl)-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
White solid, 81%yield, 90%ee.Analytical data for P11:[α]
D 20=+165.2 ° of (c=1.0, CHCl
3) .Mp=130-131 ℃.
1H NMR (300MHz, CDCl
3) δ 2.32 (s, 6H), 2.46 (d, J=2.1Hz, 2H), 3.82-3.91 (m, 3H), 4.04-4.06 (m, 2H), 6.47 (d, J=10.5Hz, 1H), 6.76 (dd, J=3.0,10.5Hz, 1H), 6.98 (s, 1H), 7.14 (s, 2H);
13C NMR (75MHz, CDCl
3) δ 21.4,41.4,62.8,66.3,76.9,79.3,124.4,130.4,132.7,138.2,138.4,149.0,196.7; IR (KBr) 2970,2918,2887,1689,1602,1454,1401,1277,1209,1174,1112,1095,1017,1001,925,854,807,703,679cm
-1HRMS (EI): high resolution mass spectrum calculating value C
16H
18O
3: 258.1256. measured value: 258.1254. chirality test condition: Daicel Chiralpak AS-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 8.94min, t
R(minor)=15.36min.
P12:(4aS, 8aS)-8a-(3, the 5-bis trifluoromethyl phenyl)-2,3,4a, 5-tetrahydro benzo [b] [1,4] two oxa-glutinous rehmannia-6 (8aH)-ketone
P12：(4aS，8aS)-8a-(3，5-bis(trifluoromethyl)phenyl)-2，3，4a，5-tetrahydrobenzo[b][1，4]dioxin-6(8aH)-one
Faint yellow oily thing, 93%yield, 88%ee.Analytical data for P12:[α]
D 20=+94.3 ° of (c=1.0, CHCl
3).
1H NMR (400MHz, CDCl
3) δ 2.39-2.58 (m, 2H), 3.91-3.98 (m, 4H), 4.08-4.12 (m, 1H); 6.58 (d, J=10.4Hz, 1H), 6.74 (dd, J=2.4,10.4Hz, 1H), 7.90 (s, 1H), 8.01 (s, 2H);
13C NMR (100MHz, CDCl
3) δ 40.9,62.8,66.3,76.3,78.9,122.8 (m), 123.0 (q, J=272.9), 127.2 (m), 132.1 (q, J=33.5Hz), 134.2,141.6,146.5,195.2;
19F NMR (282MHz, CDCl
3) δ-63.2; IR (KBr) 2965,2924,2869,1698,1625,1464m 1374,1279,1124,1001,897,844,798,706,682,673cm
-1HRMS (EI): high resolution mass spectrum calculating value: C
16H
12O
3F
6: 366.0691. measured value: 366.0694. chirality test condition: Daicel Chiralpak AS-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 7.15min, t
R(minor)=12.57min.
Embodiment 3: the conversion of oxa-Michael product P 4
P13:(4aS, 8aS)-8a-phenyl hexahydrobenzene [b] [1,4] two oxa-glutinous rehmannia-6 (7H)-ketone also
P13：(4aS，8aS)-8a-phenylhexahydrobenzo[b][1，4]dioxin-6(7H)-one
Under the argon shield, in an exsiccant reaction tubes, add Compound P 4 (23.0mg, 0.1mmol), methyl alcohol (2mL), 10% palladium carbon (2.3mg). through hydrogen exchange three times, room temperature reaction to raw material disappears under 1 normal atmosphere.Reaction solution is through diatomite filtration, and uses methanol wash.Decompression is revolved and is desolvated, residue through plate layer chromatography separate product P 13 (19.7mg, 85%yield, 99%ee).
Analytical data for P13:[α]
D 20=+68.5 ° of (c=0.5, CHCl
3) .Mp=90-91 ℃.
1HNMR (300MHz, CDCl
3) δ 1.95-1.98 (m, 1H), 2.29-2.36 (m, 1H), 2.59-2.71 (m, 3H), 3.08 (dd, J=7.2,14.4Hz, 1H), and 3.56-3.68 (m, 1H), 3.71-3.80 (m, 2H), 3.96-4.02 (m, 1H), 4.60 (t, J=6.0Hz, 1H), 7.35-7.46 (m, 3H), and 7.56-7.59 (m, 2H);
13C NMR (75MHz, CDCl
3) δ 32.1,37.2,42.3,60.6,61.9,74.6,74.8,126.4,128.0,128.8,141.2,208.6; IR (KBr) 2968,2920,2872,1725,1495,1445,1417,1280,1227,1099,1066,966,901,760,705,643,537cm
-1HRMS (EI): high resolution mass spectrum calculating value C
14H
16O
3: 232.1103. measured value: 232.1099. chirality test condition: Daicel ChiralpakAS-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 23.56min, t
R(minor)=36.30min.
P14:(4aS, 8aS)-8a-phenyl-2,3,4a, 5,6, the 8a-hexahydrobenzene is [b] [1,4] two oxa-glutinous rehmannias also
P14：(4aS，8aS)-8a-phenyl-2，3，4a，5，6，8a-hexahydrobenzo[b][1，4]dioxine
Adding Compound P 4 in an exsiccant reaction tubes (54.0mg, 0.235mmol), methyl alcohol (3mL) and cerous compounds (106.0mg 0.285mmol), is cooled to 0 ℃, and the adding sodium borohydride (18.0mg, 0.285mmol).After reacting 0.5 hour under 0 ℃, water cancellation, ethyl acetate extraction (3 * 10mL).Organic phase saturated common salt water washing, anhydrous sodium sulfate drying filters.The decompression revolve desolventize product alcohol, need not purifying and be directly used in next step reaction.
(18.0mg 0.75mmol) and tetrahydrofuran (THF) (3mL), at room temperature, drips tetrahydrofuran (THF) (3mL) solution of above-mentioned product alcohol in above-mentioned system to add compound sodium hydrogen in an exsiccant reaction tubes successively.After at room temperature reacting 30 minutes, adding dithiocarbonic anhydride (90.0mg 1.18mmol), continues reaction after 1 hour, and the adding methyl iodide (64 μ L, 1.04mmol).After at room temperature reacting 3 hours, the saturated sodium bicarbonate solution cancellation, ethyl acetate extraction merges organic phase, and anhydrous sodium sulfate drying concentrates.(ethyl acetate: sherwood oil=1: 5) separation obtains compound (50.3mg, two steps, 67% yield) to resistates through column chromatography.Above-mentioned product is dissolved in the dry toluene (4mL), reflux under argon shield, drip tributyl tin hydrogen (102 μ L, 0.37mmol) and Diisopropyl azodicarboxylate (5.0mg, toluene solution 0.03mmol) (3mL).After the back flow reaction 5 hours, be cooled to room temperature, decompression is revolved and is desolventized, resistates through column chromatography purification (ethyl acetate/petroleum ether, 1: 10) Compound P 14 (30.2mg, 87%yield, 99%ee).
Analytical data for P14:[α]
D 20=+127.3 ° of (c=1.0, CHCl
3).
1H NMR (400MHz, CDCl
3) δ 1.53-1.61 (m, 1H), 1.66-1.73 (m, 1H), 1.95-2.03 (m, 1H), 2.23-2.33 (m, 1H), 3.69-3.73 (m, 2H), 3.80-3.92 (m, 2H), 3.99-4.06 (m, 1H), 5.59-5.63 (m, 1H), 6.26-6.31 (m, 1H), 7.26-7.35 (m, 3H), and 7.55-7.58 (m, 2H);
13C NMR (75MHz, CDCl
3) δ 20.8,24.4,61.9,66.4,76.4,76.5,127.5,127.6,127.6,127.9,132.9,143.2; IR (KBr) 2955,2929,2858,1491,1447,1252,1123,1100,1026,946,908,757,700cm
-1HRMS (EI): high resolution mass spectrum calculating value C
14H
16O
3: 216.1157. measured value: 216.1150. chirality test condition: Daicel Chiralcel OJ-H (25cm), normal hexane/Virahol=70/30,1.0mL/min
-1, λ=220nm, t
R(major)=and 13.61min, t
R(minor)=34.86min.
Embodiment 4: Herba Clerodendri Indici element (C, D, asymmetric synthesis F)
In the 250mL reaction flask, add p-hydroxyphenylethanol 2 (276mg successively, 2mmol) and water (32mL), the stirring at room dissolving. slowly add potassium hydrogen persulfate (9.8g in batches, 16mmol) and sodium bicarbonate (4.2g, mixture 50mmol) at room temperature react to raw material and disappear. add shrend and go out, ethyl acetate extraction, merge organic phase, anhydrous sodium sulfate drying, filtering and concentrating.Resistates is through plate layer chromatography purifying (ethyl acetate: sherwood oil=2: 1) get Compound P 15 (130mg, 38% productive rate).
1H?NMR(300MHz，D
2O)δ1.98(t，J＝6.9Hz，2H)，3.55(t，J＝6.9Hz，2H)，6.34(d，J＝9.9Hz，2H)，7.09(d，J＝9.9Hz，2H)。
In the exsiccant reaction tubes, add successively above-mentioned product P 15 (51.0mg, 0.3mmol), CH
2Cl
2(6mL), and the chiral phosphorus acid catalyst (22.8mg, 10mol%) and activatory
Molecular sieve (150mg).At room temperature reacted 2 hours, through diatomite filtration, washed with dichloromethane.In above-mentioned methylene dichloride filtrate, add (triphenyl phosphite (140mg, 0.45mmol).At room temperature react 0.5h, decompression is revolved and is desolventized, and (ethyl acetate: (two steps are totally 57% productive rate, 80%ee) sherwood oil=2: 1) to get the plain F of Herba Clerodendri Indici through the plate layer chromatography purifying for resistates.
The plain F:[α of Analytical data for Herba Clerodendri Indici]
D 20=+29 ° of (c=0.2, CH
3OH), [document (Wenderski, T.A.; Huang, S.L.; Pettus, T.R.R.J.Org.Chem.2009,74,4104-4109): [α]
D 20=+59 ° of (c=1.0, CH
3OH)].
1H NMR (300MHz, CDCl
3) δ 2.10-2.31 (m, 2H), 2.48-2.74 (m, 2H), 3.80 (br, 1H), 3.85 (dd, J=8.4,15.0Hz, 1H), 3.99 (dd, J=8.4,15.0Hz, 1H), 4.15 (t, J=4.5Hz, 1H), 5.92 (d, J=9.9Hz, 1H), 6.71 (d, J=9.9Hz, 1H);
13C NMR (75MHz, CDCl
3) δ 39.3,39.9,66.2,75.1,81.2,128.3,148.7,197.6; Chirality test condition: Daicel Chiralpak IC (25cm), normal hexane/Virahol=70/30,0.8mL/min
-1, λ=220nm, t
R(minor)=and 8.64min, t
R(major)=9.63min.
Under argon shield, in the dry reaction pipe, add successively the plain F of Herba Clerodendri Indici (30.3mg, 0.2mmol), methyl alcohol (2mL), 10% palladium carbon (6.0mg).Through hydrogen exchange three times, room temperature reaction to raw material disappears under 1 normal atmosphere.Through diatomite filtration, and use methanol wash, decompression is revolved and is desolvated, residue through plate layer chromatography (ethyl acetate: sherwood oil=2: 1) purifying get the plain C of product Herba Clerodendri Indici (94% productive rate, 81%ee).
The plain C:[α of Analytical data for Herba Clerodendri Indici]
D 20=-50.0 ° of (c=1.0, CH
3OH), [document (Wenderski, T.A.; Huang, S.L.; Pettus, T.R.R.J.Org.Chem.2009,74,4104-4109): [α]
D 20=-79 ° of (c=0.1, CH
3OH)].
1H NMR (300MHz, CDCl
3) δ 2.09-2.13 (m, 4H), 2.22-2.32 (m, 1H), 2.45-2.61 (m, 3H), 2.71-2.78 (m, 1H), 3.87-3.99 (m, 3H);
13CNMR (75MHz, CDCl
3) δ 33.3,35.0,40.4,42.3,65.9,77.3,83.4,210.4; Chirality test condition: chiral GC analysis (Rt-β DEX 30m * 0.25mm * 0.25um) 60 ℃-180 ℃, 5 ℃/min, 12psi) t
R(major)=and 51.91min, t
R(minor)=54.49min.
The plain D of Herba Clerodendri Indici
In the exsiccant reaction tubes, add successively Compound P 15 (51.0mg, 0.3mmol), methylene dichloride (6mL), the chiral phosphorus acid catalyst (22.8mg, 10mol%) and activatory
Molecular sieve (150mg). after at room temperature reacting 2 hours, being added dropwise to the methanol solution (30 μ L) of benzyltrimethylammonium hydroxide (40%). reaction is after 30 minutes under the room temperature, through diatomite filtration, washed with dichloromethane, the decompression revolve desolventize epoxy compounds (containing the chiral phosphorus acid catalyst), need not purifying, be directly used in next step reaction.
In reaction tubes, add above-mentioned epoxy compounds successively, tetrahydrofuran (THF) (4mL), ethanol (1.6mL), water (1.6mL) and saturated sodium bicarbonate (0.4mL) at room temperature add freshly prepd aluminium amalgam.Vigorous stirring reaction disappears to raw material.Diatomite filtration, washing with alcohol, filtrate merges organic phase through ethyl acetate extraction.Anhydrous sodium sulfate drying filters, and under reduced pressure revolves to desolventize, and resistates gets the plain D of compound Herba Clerodendri Indici (13.8mg, three steps are totally 27% productive rate) through column chromatography purification (ethyl acetate).
Analytical data for compound P16 (80%ee):
1H NMR (300MHz, CDCl
3) δ 2.12-2.19 (m, 1H), 2.28-2.34 (m, 1H), 2.67-2.97 (m, 2H), 3.98-4.03 (m, 2H), 4.56 (t, J=5.1Hz, 1H), 6.17 (d, J=10.2Hz, 1H), 6.84 (d, J=10.2Hz, 1H), 8.56 (br, 1H);
13CNMR (100MHz, CDCl
3) δ 36.4,41.2,66.1,78.8,86.6,130.7,146.7,197.2; Chirality test condition: Daicel Chiralpak AD-H (25cm), normal hexane/Virahol=80/20,1.0mL/min
-1, λ=220nm, t
R(major)=and 6.08min, t
R(minor)=7.01min.
The plain D:[α of Analytical data for Herba Clerodendri Indici]
D 20=-63 ° of (c=0.2, CH
3OH), [document [α]
D 20=-38 ° of (c=0.5, CH
3OH); Wenderski, T.A.; Huang, S.L.; Pettus, T.R.R.J.Org.Chem.2009,74,4104-4109.].
1H NMR (400MHz, CDCl
3) δ 2.12-2.16 (m, 2H), 2.63-2.56 (m, 3H), 2.77 (br, 1H), 2.92 (dd, J=3.6,12.6Hz, 1H), 2.94 (br, 1H), 3.89-3.93 (m, 1H), 3.99-4.02 (m, 2H), 4.13 (br, 1H);
13C NMR (75MHz, CDCl
3) δ 38.7,41.6,42.2,66.1,70.9,78.6,82.7,207.4.
Claims (8)
1. 4-oxa-compound and furan compound have following structural formula:
R wherein
1Be selected from the alkyl of H or C1-C16 arbitrarily; R wherein
2Be selected from OH, OOH, C arbitrarily
3-C
16Cycloalkyl, C
4-C
10The aryl that replaces of the heterocyclic radical that contains N, O or S, aryl, R; Described aryl is a phenyl or naphthyl; R is C
1-C
4Alkyl, C
1-C
4Perfluoroalkyl, halogen or C
1-C
4Alkoxyl group; Wherein X is selected from CH arbitrarily
2Or OCH
2
2. one kind as claimed in claim 11, the synthetic method of 4-oxa-compound and furan compound, it is characterized in that in-78 ℃ to 100 ℃ and organic solvent, with the cyclohexadiene ketone derivatives is raw material, with chirality phosphoric acid is that catalyzer carries out intramolecularly oxa-Michael reaction 30 minutes-48 hours, and the mol ratio of described cyclohexadiene ketone derivatives and chirality phosphoric acid is 1: 0.01-0.5; Wherein, described cyclohexadiene ketone derivatives structural formula is as follows:
The structural formula of described catalyzer is
R wherein
1, R
2Or X according to claim 1; R
8, R
9, R
10, R
11Or R
12Be selected from alkyl, thriaryl-silicon, replacement or the unsubstituted aryl of H, C1-C16 arbitrarily; Described aryl is naphthyl, anthryl or phenanthryl.
3. as claimed in claim 2 synthetic 1, the method of 4-oxa-compound and furan compound is characterized in that described organic solvent is benzene, tetracol phenixin, sherwood oil, tetrahydrofuran (THF), dimethyl formamide, ether, methylene dichloride, trichloromethane, toluene, dimethylbenzene, hexanaphthene, normal hexane, normal heptane, dioxane or acetonitrile.
4. as claimed in claim 2 synthetic 1, the method for 4-oxa-compound and furan compound is characterized in that products therefrom is through in addition separation and purification of recrystallization, thin-layer chromatography, column chromatography or underpressure distillation.
5. the purposes of a furan compound as claimed in claim 1 is characterized in that being used to be prepared as follows structural formula
6. purposes as claimed in claim 5, it is characterized in that in organic solvent and room temperature under, furan compound as claimed in claim 1 and reductive agent reaction obtained the plain F compound of Herba Clerodendri Indici in 1-72 hour, and the mol ratio of described furan compound and reductive agent is 1: 1-5; Described reductive agent is S-WAT, Sulfothiorine, triphenyl phosphite or triphenyl phosphorus.
7. purposes as claimed in claim 5, it is characterized in that in organic solvent and room temperature under, the plain F compound of Herba Clerodendri Indici as claimed in claim 6 obtained the plain C compound of Herba Clerodendri Indici in 1-72 hour in the reaction of palladium hydrocarbonize, plain F compound of described Herba Clerodendri Indici and palladium carbon 1: 0.01-0.2.
8. purposes as claimed in claim 5, it is characterized in that in organic solvent and room temperature under, furan compound as claimed in claim 1 and salt of wormwood, yellow soda ash or benzyltrimethylammonium hydroxide reacted 1-72 hour, followed and the plain D compound of reductive agent reaction acquisition in 1-72 hour Herba Clerodendri Indici; Described reductive agent is triethyl-boron aluminum hydride, aluminium amalgam or Lithium Aluminium Hydride; The mol ratio of described furan compound and salt of wormwood, yellow soda ash or benzyltrimethylammonium hydroxide is 1: 0.1-0.5; The mol ratio of described furan compound and reductive agent is 1: 1-10.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010114566.9A CN101812046B (en) | 2010-02-26 | 2010-02-26 | Furan compound, synthetic method and applications |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201010114566.9A CN101812046B (en) | 2010-02-26 | 2010-02-26 | Furan compound, synthetic method and applications |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101812046A true CN101812046A (en) | 2010-08-25 |
| CN101812046B CN101812046B (en) | 2014-02-19 |
Family
ID=42619427
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201010114566.9A Expired - Fee Related CN101812046B (en) | 2010-02-26 | 2010-02-26 | Furan compound, synthetic method and applications |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101812046B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105111228A (en) * | 2015-08-28 | 2015-12-02 | 南京大学 | Chiral phosphoric acid with 5,5'-bitetralone skeleton and preparation method thereof |
| CN113248480A (en) * | 2021-05-12 | 2021-08-13 | 常州大学 | Method for inserting 2-pyridone or 3-pyridazinone N-H bond in furan carbene chemoselectivity and enantioselectivity |
-
2010
- 2010-02-26 CN CN201010114566.9A patent/CN101812046B/en not_active Expired - Fee Related
Non-Patent Citations (3)
| Title |
|---|
| 《Chinese Chemical Letters》 20011231 Jin CHEN，et al. First Total Synthesis of Cleroindicin B, ( ) Cleroindicin C and E 771-774 1-8 第12卷, 第9期 * |
| 《J. Nat. Prod.》 19971231 Jun Tian,et al. New Cleroindicins from Clerodendrum indicum 第766-769页 1-8 第60卷, 第8期 * |
| 《J. Org. Chem.》 20090507 Todd A. Wenderski, et al. Enantioselective Total Synthesis of All of the Known Chiral Cleroindicins (C-F): Clarification Among Optical Rotations and Assignments 第4104-4109页 1-8 第74卷, 第11期 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105111228A (en) * | 2015-08-28 | 2015-12-02 | 南京大学 | Chiral phosphoric acid with 5,5'-bitetralone skeleton and preparation method thereof |
| CN113248480A (en) * | 2021-05-12 | 2021-08-13 | 常州大学 | Method for inserting 2-pyridone or 3-pyridazinone N-H bond in furan carbene chemoselectivity and enantioselectivity |
| CN113248480B (en) * | 2021-05-12 | 2023-08-22 | 常州大学 | Method for chemically and enantioselectively inserting N-H bond of 2-pyridone or 3-pyridazinone into furan carbene |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101812046B (en) | 2014-02-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106365949B (en) | Chiral spiroindane skeleton compound and preparation method thereof | |
| JP2008239495A (en) | Method for producing optically active epoxy compound, complex to be used in the method and method for producing the same | |
| JP6487568B2 (en) | Kinetic resolution by catalytic asymmetric hydrogenation of racemic δ-hydroxy ester and its application | |
| CN102153501B (en) | Chiral nitrogen-containing heterocyclic compound, and synthesis method and application thereof | |
| KR20160101055A (en) | Synthesis of isohexide ethers and carbonates | |
| CN101812046B (en) | Furan compound, synthetic method and applications | |
| CN111718372B (en) | Axial chiral phosphine-alkene ligand and preparation method and application thereof | |
| Tsou et al. | Enantioselective organocatalytic vinylogous aldol-cyclization cascade reaction of 3-alkylidene oxindoles with o-quinones | |
| CN103073590B (en) | Chirality fragrance Spiroketals skeleton biphosphine ligand and its preparation method and application | |
| CN109810125A (en) | The preparation method of chiral copper complex and preparation method thereof, chiral unsaturated beta-nitro alpha-hydroxy esters | |
| CN102344431A (en) | Method for preparing nebivolol hydrochloride | |
| Sakai et al. | Biomimetic Construction of a syn-2, 7-Dimethyloxepane Ring via 7-Endo Cyclization | |
| CN113004296A (en) | General synthetic method for preparing chiral oxygen heterocyclic compound by novel [4+1] and [5+1] cyclization strategies | |
| CN115850304A (en) | Method for stereoselectively preparing 2-alkyl-4-boron-based heterocyclic compound | |
| CN110317170B (en) | Green synthesis method of 3-phenanthridinyl propyl formate compound | |
| CN109265385B (en) | Synthesis process of chiral catalyst | |
| Martinková et al. | A stereoselective total synthesis of the HCl salts of mycestericins F, G and ent-F | |
| CN109776610B (en) | Chiral P, N, N ligand compound based on phenylethylamine skeleton, preparation method and application | |
| CN114835694B (en) | Method for synthesizing chiral 3, 4-dihydro-2H-pyran compounds in aqueous medium | |
| CN100371334C (en) | Method for preparing (S)-3-hydroxy group-gamma-butyrolactone | |
| KR20130041792A (en) | Method for producing acyloxypyranone compound, method for producing alkyne compound, and method for producing dihydrofuran compound | |
| CN112939830B (en) | Nucleophilic reaction method of alkenyl thioether to o-methylene benzoquinone | |
| CN114835694A (en) | Method for synthesizing chiral 3, 4-dihydro-2H-pyran compound in aqueous medium | |
| CN113912575A (en) | Chiral polysubstituted tetrahydrofuran acetal, preparation method thereof and preparation method of lignans natural product | |
| Liu et al. | A new approach for the asymmetric total synthesis of umbelactone |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20140219 Termination date: 20190226 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |