CN1216023C - Method for preparing trans-(+)-hydrated pinanol - Google Patents
Method for preparing trans-(+)-hydrated pinanol Download PDFInfo
- Publication number
- CN1216023C CN1216023C CN 03118136 CN03118136A CN1216023C CN 1216023 C CN1216023 C CN 1216023C CN 03118136 CN03118136 CN 03118136 CN 03118136 A CN03118136 A CN 03118136A CN 1216023 C CN1216023 C CN 1216023C
- Authority
- CN
- China
- Prior art keywords
- methyl
- hours
- acyl group
- room temperature
- methoxy acyl
- 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.)
- Expired - Fee Related
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a method for preparing inverse-(+)-hydrate pinol. The present invention takes 3, 5-dihydroxy-4-methylbenzoic acid methyl ester as raw materials, and synthesizes inverse-(+)-hydrate pinol by the procedure of catalytic hydrogenation, lipase catalyzed asymmetrical acylation, Mistunobu configuration conversion, etc. The total yield of the inverse-(+)-hydrate pinol prepared by the present invention reaches 26%, and the optical purity is greater than 99%. The present invention has little side reaction and easy reaction operation, and is suitable for developing medicine to cure disease, such as bronchitis, asthma, etc.
Description
Technical field: the present invention relates to the preparation of terpinum compounds, be specifically related to the preparation of trans-(+)-sobrerol.
Background technology: trans-sobrerol (trans-sobrerol), have another name called trans-Sobrerol, belong to the terpinum compounds, it is a kind of mucolysis medicine, has the eliminating phlegm and relieving asthma effect, is mainly used in diseases such as treatment bronchitis and asthma.This compound of discovering in recent years has the pharmacological action of inducing apoptosis of tumour cell, is expected to become new cancer therapy drug.In addition, this compound also can be used as a kind of important chiral source reagent in the organic synthesis field.
Trans-(±)-sobrerol of racemic modification some chemistry and drugmaker (as Aldrich-Sigma) abroad is on sale, and it is by α-Pai Xi oxidation and generating in the presence of light or daylight.Yet studies show that have pharmacological action be optically pure trans-(+)-sobrerol, synthetic for this compound, existing reported method has: α-Pai Xi is at Cu (Pyridine)
2Cl
2Deng being oxidized to (+)-2 under the ligand transition metal catalysis, 3-epoxy-suitable-pinane, then at aqueous phase through acid catalysis or RuCl
3The catalysis open loop can get (Rothemberg G., Yatziv Y., Sasson Y., Tetrahedron, 1998,54:593), the deficiency of this method is that side reaction is many, chemical yield not high (<15%), and the product optical purity is low.Another kind method be adopt the catalytic kinetic resolution of racemic body of lipase get the optical purity product (Bovara R., CarraraG., Ferrara L., Tetrahedron Asymmetry, 1991,2:931), this method is not suitable for the technical scale preparation.
Summary of the invention: the objective of the invention is to study a kind of efficient, be fit to the mass preparation optical purity trans-novel method of (+)-sobrerol, to remedy above-mentioned deficiency, be applicable to drug development and synthetic high-optical-purity chiral source reagent simultaneously.
The technical scheme that realizes the object of the invention is as follows: raw material is 3, and 5-dihydroxyl-methyl 4 methylbenzoate (2) is at Rh/Al
2O
3Following and the H of catalysis
2It is suitable that effect got the catalytic hydrogenation product in 20 hours through the high pressure-temperature reaction; suitable; suitable-3; 5-dihydroxyl-4-methyl isophthalic acid-(methoxy acyl group) hexanaphthene (3); (3) under Pseudomonas fluorescens lipase (Ps.fluorescens) catalysis with vinyl-acetic ester room temperature reaction 60~80 hours; asymmetric acetyl glycosylation reaction takes place get high optically pure (1R; 3S; 4S; 5R)-5-acetoxy-3-hydroxy-4-methyl-1-(methoxy acyl group) hexanaphthene (4); (4) behind tert-butyl diphenyl chlorosilane (TBDPSCl) protection hydroxyl, use anhydrous K
2CO
3/ MeOH room temperature reaction got deacetylation product (5) in 6~8 hours; (5) in the presence of diethylazodicarboxylate (DIAD) and triphenylphosphine through Mitsunobu eliminate react substituted cyclohexene alcohol (6); (6) in the tetrahydrofuran solution of tetrabutylammonium (TBAF) under the room temperature through 12~18 hours the deprotection base (TBDPS) compound (7); (7) in the presence of diethylazodicarboxylate (DIAD) and triphenylphosphine, at room temperature reacted 8~12 hours with p-nitrobenzoic acid; get p-nitrobenzoic acid ester (8) through the Mitsunobu configuration conversion, (8) are in anhydrous K
2CO
3Took off the substituted cyclohexene alcohol (9) that the p-nitrophenyl formyl radical gets configuration conversion in 6~9 hours with reacting under the room temperature in the dry methyl alcohol, (9) through with Grignard reagent MeMgBr under cold condition, react 5~9 hours optically pure trans-(+)-sobrerol (1).
The present invention relates to compound trans-(+)-sobrerol, its available following formula characterizes.
It is a kind of eliminating phlegm and relieving asthma medicine, can be used for treating diseases such as bronchitis, asthma.
Trans-(+)-sobrerol can be by following reactions steps preparation.
In above reactions steps, raw material 3,5-dihydroxyl-methyl 4 methylbenzoate (2) is at 5%Rh/Al
2O
3Following and the H of catalysis
2Effect is through high pressure-temperature (110~140atm; 90~110 ℃) reacted 20 hours to such an extent that the catalytic hydrogenation product is suitable; suitable; suitable-3; 5-dihydroxyl-4-methyl isophthalic acid-(methoxy acyl group) hexanaphthene (3); (3) under 30~60% Pseudomonas fluorescens lipase (Ps.fluorescens) catalysis of substrate weight with vinyl-acetic ester room temperature reaction 60~80 hours; asymmetric acetyl glycosylation reaction takes place get high optically pure (1R; 3S; 4S; 5R)-and 5-acetoxy-3-hydroxy-4-methyl-1-(methoxy acyl group) hexanaphthene (4), (4) are behind 1.0~1.5 equivalent tert-butyl diphenyl chlorosilanes (TBDPSCl) protection hydroxyl, with 1.0~3.0 equivalent anhydrous K
2CO
3/ MeOH room temperature reaction got deacetylation product (5) in 6~8 hours; (5) in the presence of 3.0~5.0 equivalent diethylazodicarboxylates (DIAD) and 3.0~5.0 equivalent triphenylphosphines through Mitsunobu eliminate react substituted cyclohexene alcohol (6); (6) in the tetrahydrofuran solution of 1.0~2.0 equivalent tetrabutylammonium (TBAF) under the room temperature through 12~18 hours the deprotection base (TBDPS) compound (7); (7) at room temperature get p-nitrobenzoic acid ester (8) through reaction in 8~12 hours through the Mitsunobu configuration conversion with 1.1~1.5 equivalent p-nitrobenzoic acids in the presence of 1.0~3.0 equivalent diethylazodicarboxylates (DIAD) and 1.0~3.0 equivalent triphenylphosphines, (8) are in 1.0~2.0 equivalent anhydrous K
2CO
3Took off the substituted cyclohexene alcohol (9) that the p-nitrophenyl formyl radical gets configuration conversion in 6~9 hours with reacting under the room temperature in the dry methyl alcohol, (9) are through reacting trans-(+)-sobrerol (1) compound that got optical purity (ee>99%) in 5~9 hours with 4.0~6.0 equivalent Grignard reagent MeMgBr under-50~-78 ℃ of temperature.Measure by analysis, the physicochemical property parameter of trans-(+)-sobrerol is as follows: m.p.130-132 ℃, [α]
D R.t=+133.4 (c 0.31, CHCl
3), ee>99%.IR (film): n=3274,2973,1629,1468,1425,1376,1294,1251,1156,1052,984,920,824,761,662,611,468cm
-1.
1HNMR (500MHz, CDCl
3): δ=5.58 (q, J=1.4Hz, 1H), 4.05 (s, 1H), 2.13 (m, 1H), 2.01 (dd, J=13.4,1.4Hz, 1H), 1.80 (s, 3H), 1.78-1.70 (m, 1H), 1.54 (br s, 2H), 1.45~1.30 (m, 2H), 1.22 (s, 2H), 1.19 (s, 3H) ppm.
13CNMR (50MHz, CDCl
3): δ=134.5,125.5,72.4,68.8 39.0,32.9,27.7,27.2,27.0,21.0ppm.MS m/z (%): 152 (M
+-18,6), 149 (7), 137 (10), 119 (5), 109 (55), 97 (8), 95 (15), 79 (50), 69 (25), 59 (90), 55 (35), 43 (100). ultimate analysis C
10H
18O
2(170.25): calculated value (%): C, 70.55; H, 10.66. experimental value (%): C, 70.61; H, 10.85.
We are with easy acquisition 3, and 5-dihydroxyl-methyl 4 methylbenzoate is a raw material, through 8 step reactions (overall yield is 26%) prepare optically pure trans-(+)-water contains pinol (ee>99%).This method side reaction is few, and operation is easy, and the chemical yield height, and the optical purity of product is high, has the very strong market competitiveness.
Embodiment:
1, suitable, suitable, suitable-3, the making of 5-dihydroxyl-4-methyl isophthalic acid-(methoxy acyl group) hexanaphthene 3
With 3,5-dihydroxyl-methyl 4 methylbenzoate (90g), 5%Rh/Al
2O
3(9g, 10%), methyl alcohol (750ml) and acetate (2ml) add in the stainless steel high-pressure reaction pot of 1L after mixing, and use H
2(from 130 to 40 normal atmosphere) purges high-pressure reaction pot 2 times, with H
2Pressure is raised to 130 normal atmosphere, and 105 ℃ of temperature were reacted 20 hours with this understanding, reaction mixture is through diatomite filtration, catalyst recovery, filtrate concentrates, and residue recrystallization in ethyl acetate-iso-pentane (4: 1) mixed solvent gets 55g crystalloid title compound (productive rate 62%).m.p.127-128℃.IR(KBr)n=3380,2915,1730,1438,1362,1268,1198,1022,740cm
-1,
1HNMR(500MHz,CDCl
3,δppm):3.85(br.s.2H),3.31(s,3H),2.60(t,J=5.3Hz,1H),2.22(br.s,2H),1.84-1.80(m,4H),1.11(d,J=7.1Hz,3H),MS?m/z(%):189(M
++1,2),170(15),152(18),127(85),111(95),95(58),87(100),67(70),55(80)。
2, (1R, 3S, 4S, 5R)-the making of 5-acetoxy-3-hydroxy-4-methyl-1-(methoxy acyl group) hexanaphthene 4
In flask, add suitable; suitable; suitable-3; 5-dihydroxyl-4-methyl isophthalic acid-(methoxy acyl group) hexanaphthene (10.0g; 55.0mmol); Pseudomonas fluorescens lipase Lipase (Ps.fluorescens) (6.5g; 42.5U/mg) and vinyl-acetic ester (250ml); mixture reacted 72 hours under room temperature lucifuge condition; reaction mixture is by diatomite filtration, and filtrate concentrates, residue flash silica gel column purifying; iso-pentane-ethyl acetate (7: 3) wash-out gets 11.8g oily title compound (productive rate: 93%).[α]
D r.t=-21.9(C0.81,CHCl
3),ee>99%。IR (film): n=3437,2953,1730,1472,1439,1365,1242,1197,1178,1078,1026,981,875cm
-1.
1HNMR (500MHz, CDCl
3), δ=4.81 (m, 1H), 3.81 (m, 1H), 3.69 (s, 3H), 2.45 (m, 1H), 2.30 (d, J=6.4Hz, 1H), 2.05 (s, 3H), 1.92 (m, 2H), 1.77 (m, 3H), 0.96 (d, J=7.0Hz, 3H) ppm.
13CNMR (50MHz, CDCl
3), δ=174.6,170.3,72.1,69.6,52.0,38.0 37.6,30.5,27.3,21.2,6.21ppm.MS:m/z=(%): 231 (M
++ 1,1), 213 (2), 199 (4), 186 (5), 170 (15), 152 (21), 127 (60), 111 (70), 93 (75), 87 (25), 82 (20), 43 (100). ultimate analysis C
11H
18O
5, calculated value (%): C, 57.38; H, 7.88. experimental value (%): C, 57.21; H, 7.95.
3, (1S, 3R, 4R, 5S)-the making of 5-tert-butyl diphenyl siloxy-3-hydroxy-4-methyl-1-(methoxy acyl group) hexanaphthene 5
In flask, put into (1R, 3S, 4S; 5R)-5-acetoxy-3-hydroxy-4-methyl-1-(methoxy acyl group) hexanaphthene (8.1g; 35.2mmol), imidazoles (7.2g, 105.7mmol), dimethylamine pyridine (DMAP) (200mg) and exsiccant methane amide (DMF) (120ml).Under constantly stirring, drip tert-butyl diphenyl chlorosilane (TBDPSCl) (18ml, 70.4mmol, 98%).Reaction mixture at room temperature stirred 20 hours, toppled over then in entry-ethyl acetate (600ml, V/V, 5: 5), and organic layer separates, and water layer merges organic layer saturated aqueous common salt (150ml * 3) washing, anhydrous MgSO with ethyl acetate (200ml * 3) extraction
4Drying concentrates to such an extent that slightly produce, and this crude product is dissolved in the dry methyl alcohol of 150ml, adds anhydrous K
2CO
3(980mg), at room temperature stirring reaction is 6 hours, and (300ml: 200ml) distribute, organic layer separates, and water layer extracts with ethyl acetate (300ml * 3), and organic layer merges, anhydrous MgSO with ethyl acetate one water
4Drying concentrates, residue flash silica gel column purifying, and iso-pentane-ethyl acetate (9: 1) wash-out gets 6.9g oily title compound (productive rate 98%).[α]
D R.t=+33.0 (c 0.62, CHCl
3) .IR (film): n=3448,2954,2858,1737,1654,1472,1362,1279,1240,1173,1008,852,822,795,741,702,611cm
-1.
1HNMR (500MHz, CDCl
3), δ=7.65 (m, 4H), 7.44 (m, 2H), 7.37 (m, 4H), 3.69 (m, 1H), 3.64 (s, 3H), 3.51 (m, 1H), 2.16 (m, 1H), 2.08 (m, 1H), 1.77 (m, 1H), 1.69 (t, J=8.9Hz, 2H), 1.56 (q, J=12.4Hz, 1H), 1.37 (d, J=5.3Hz, 1H), 1.06 (s, 9H), 1.02 (d, J=7.0Hz, 3H) .MS:m/z (%): 409 (1), 369 (7), 337 (7), 309 (5), 291 (35), 199 (100), 156 (85), 181 (17), 153 (34), 121 (23), 93 (68), 57 (47). ultimate analysis C
25H
34O
4Si, calculated value (%): C, 70.38; H, 8.03. experimental value (%): C, 70.55; H, 7.91.
4, (4S, 6S)-the making of 6-tert-butyl diphenyl siloxy-1-methyl-4-(methoxy acyl group) tetrahydrobenzene 6
In flask, put into (1S, 3R, 4R, 5S)-5-tert-butyl diphenyl siloxy-3-hydroxy-4-methyl-1-(methoxy acyl group) hexanaphthene (19.0g, 45.0mmol), Ph
3P (57.7g, 220mmol), 300ml (tetrahydrofuran (THF)), under stirring at room, drip diethylazodicarboxylate (DIAD) (41ml, 220mmol).After 18 hours, reaction mixture concentrates, residue flash silica gel column chromatography, and iso-pentane-ethyl acetate (95: 5) wash-out gets 16.7 oily title compounds (productive rate 92%).[α]
D R.t=+81.8 (c 1.52, CHCl
3) .IR (film): n=2952,2857,1738,1589,1472,1429,1362,1308,1247,1169,1111,1062,1000,934,821,740,703cm
-1.
1HNMR (500MHz, CDCl
3, δ=7.73~7.37 (m, 10H), 5.39 (m, 1H), 4.24 (s, 1H), 3.59 (s, 1H), 2.39 (m, 1H), 2.32~2.02 (m, 3H), 1.75 (m, 1H), 1.66 (s, 3H), 1.07 (s, 9H) ppm,
13CNMR (50MHz, CDCl
3), δ=175.2,137.5,136.1,134.4,133.7,129.6,127.6,121.9,71.4,51.6,38.9,35.2,27.9,27.1,20.2,19.5ppm.MS m/z (%): 408 (M
+, 1), 354 (8), 351 (M
+-57,20), 299 (5), 273 (6), 213 (100), 183 (75), 137 (70). ultimate analysis C
25H
32O
3Si, calculated value (%): C, 73.49; H, 7.89. experimental value (%): C, 73.25; H, 7.74.
5, (4S, 6S)-the making of 6-hydroxyl-1-methyl-4-(methoxy acyl group) tetrahydrobenzene 7
In flask, put into (4S; 6S)-6-tert-butyl diphenyl siloxy-1-methyl-4-(methoxy acyl group) tetrahydrobenzene (13.7g; 34mmol), the 200ml tetrahydrofuran (THF) adds tetrabutylammonium fluoride (TBAF) (180ml) (1M in THF); stirring reaction 20h at room temperature; steam solvent, residue flash silica gel column chromatography purification, iso-pentane-ethyl acetate (8: 2) wash-out; get 5.2g oily title compound (productive rate, 90%).[α]
D R.t=+16.8 (c 0.66, CHCl
3) .IR (film): n=3432,2951,2850,1735,1455,1435,1382,1247,1185,1170,1035,925cm
-1.
1HNMR (500MHz, CDCl
3), δ=5.45 (t, J=1.5Hz, 1H), 4.08 (t, J=6.2Hz, 1H), 3.68 (s, 3H), 2.71 (m, 1H), 2.30~2.20 (m, 3H), 2.15 (brs, 1H), 1.90 (m, 1H), 1.78 (s, 3H) .MS m/z (%): 170 (M
+, 3), 152 (20), 137 (15), 111 (30), 93 (100), 77 (30), 43 (50). ultimate analysis C
9H
14O
3(170.21): calculated value (%): C, 63.51; H, 8.29. experimental value (%): C, 63.31; H, 8.40.
6, (4S, 6R)-the making of 1-methyl-6-p-nitrophenyl methanoyl-4-(methoxy acyl group) tetrahydrobenzene 8
In flask, put into (4S, 6S)-6-hydroxyl-1-methyl-4-(methoxy acyl group) tetrahydrobenzene (3.5g, 16.5mmol), p-nitrobenzoic acid (3.04g, 18.2mmol), Ph
3(4.76g, 18.2mmol) with the 200ml tetrahydrofuran (THF), (34ml 18.2mmol), dropwised P in about 30 minutes to drip diethylazodicarboxylate (DIAD) under 0~10 ℃ of stirring.Reaction mixture by diatomite filtration, washs with ethyl acetate after at room temperature continuing to stir 9 hours, xanchromatic filtrate concentrates, the residue purification by silica gel column chromatography, iso-pentane-ethyl acetate (9: 1) wash-out gets 5.12g oily title compound (productive rate 78%).[α]
D r.t=+281.5(c?1.38,CHCl
3),IR(film):n=2950,1719,1607,1527,1436,1343,1267,1196,1167,1101,1013,946,921,873,848,720cm
-1.
1HNMR(500MHz,CDCl
3),δ=8.29(d,J=7.9Hz,2H),8.22(d,J=7.9Hz,2H),5.79(brs,1H),5.54(s,1H),3.69(s,3H),2.76(m,1H),2.45(d,J=17.8Hz,1H),2.32(d,J=11.6Hz,1H),2.25(t,J=13.2Hz,1H),1.96(m,1H),1.75(s,3H)ppm.
13CNMR(50MHz,CDCl
3):δ=175.5,164.5,150.8,135.9,127.1,123.7,77.8,77.2,76.5,71.2,52.0,35.1,28.0,20.9ppm.MS?m/z(%):319(M
+,1),259(8),152(20),150(75),121(20),93(100).77(40),50(30).
7, (4S, 6R)-the making of 6-hydroxyl-1-methyl-4-(methoxy acyl group) tetrahydrobenzene 9
In flask, put into (4S, 6R)-1-methyl-6-p-nitrophenyl methanoyl-4-(methoxy acyl group) tetrahydrobenzene (5.0g, 15.7mmol), 200ml methyl alcohol and anhydrous K
2CO
3(108mg, 7.85mmol) stirring reaction 8h at room temperature.Reaction mixture impouring ethyl acetate one water (300ml: 200ml), separatory, water merges organic layer with ethyl acetate (100ml * 3) extraction, with saturated aqueous common salt (60ml * 3) washing, anhydrous MgSO
4Drying concentrates, the residue purification by silica gel column chromatography, and iso-pentane-ethyl acetate (8: 2) wash-out gets 2.48g oily title compound (productive rate: 93%).[α]
D R.t=+156.3 (c0.6, CHCl
3) .IR (film): n=3406,2952,1734,1437,1250,1197,1053,966,809cm
-1.
1HNMR (500MHz, CDCl
3): δ=5.56 (q, J=1.4Hz, 1H), 4.05 (brs, 1H), 3.69 (s, 3H), 2.74 (m, 1H), 2.20-2.10 (m, 2H), 1.79 (m, 4H), 1.61 (s, 1H).
13CNMR (50MHz, CDCl
3): δ=176.0,134.4,123.8,67.3,51.8,34.3,34.2,27.9,20.8ppm, MS m/z (%): 170 (M
+, 15), 139 (15), 120 (10), 110 (70), 95 (100), 77 (70), 67 (50), 55 (80), 43 (70). ultimate analysis C
9H
14O
3(170.21): calculated value (%): C, 63.51; H, 8.29. experimental value (%): C, 63.42; H.8.37.
8, trans-(+)-sobrerol 1 makes
In flask, put into (4S, 6R)-(2.5g, 11.8mmol), the 60ml tetrahydrofuran (THF) drips MeMgBr (66ml, 3.0M in Et down at-78 ℃ to 6-hydroxyl-1-methyl-4-(methoxy acyl group) tetrahydrobenzene
2O), reaction mixture stirred 6 hours down at-78 ℃, slowly rose to room temperature, continued stirring reaction after 12 hours, with the saturated NH of 50ml
4Cl solution cancellation reaction with ethyl acetate (200ml * 3) extraction, merges organic layer, with saturated aqueous common salt (100ml * 3) washing, anhydrous MgSO
4Drying concentrates, residue flash silica gel column layer post, and iso-pentane-ethyl acetate (6: 4) wash-out, product is at CH
2Cl
2Middle crystallization gets the colourless needle-like title compound of 1.68g (productive rate 85%).M.p.130-132 ℃, [α]
D R.t=+133.4 (c 0.31, CHCl
3), ee>99%.IR (film): n=3274,2973,1629,1468,1425,1376,1294,1251,1156,1052,984,920,824,761,662,611,468cm
-1.
1HNMR (500MHz, CDCl
3): δ=5.58 (q, J=1.4Hz, 1H), 4.05 (s, 1H), 2.13 (m, 1H), 2.01 (dd, J=13.4,1.4Hz, 1H), 1.80 (s, 3H), 1.78-1.70 (m, 1H), 1.54 (br s, 2H), 1.45~1.30 (m, 2H), 1.22 (s, 2H), 1.19 (s, 3H) ppm.
13CNMR (50MHz, CDCl
3): δ=134.5,125.5,72.4,68.8 39.0,32.9,27.7,27.2,27.0,21.0ppm.MS m/z (%): 152 (M
+-18,6), 149 (7), 137 (10), 119 (5), 109 (55), 97 (8), 95 (15), 79 (50), 69 (25), 59 (90), 55 (35), 43 (100). ultimate analysis C
10H
18O
2(170.25): calculated value (%): C, 70.55; H, 10.66. experimental value (%): C, 70.61; H, 10.85.
Claims (1)
1, a kind of trans-preparation method of (+)-sobrerol, it is characterized in that this method is: raw material 3,5-dihydroxyl-methyl 4 methylbenzoate 2 is at Rh/Al
2O
3Following and the H of catalysis
2Act on 110~140atm; reaction got catalytic hydrogenation product suitable, suitable, suitable-3 in 20 hours under 90~110 ℃ of conditions; 5-dihydroxyl-4-methyl isophthalic acid-(methoxy acyl group) hexanaphthene 3; 3 under the catalysis of Pseudomonas fluorescens lipase with vinyl-acetic ester room temperature reaction 60~80 hours, asymmetric acetyl glycosylation reaction takes place get high optically pure (1R, 3S; 4S; 5R)-5-acetoxy-3-hydroxy-4-methyl-1-(methoxy acyl group) hexanaphthene 4,4 behind tert-butyl diphenyl chlorosilane protection hydroxyl, use anhydrous K
2CO
3/ MeOH room temperature reaction got deacetylation product (1S in 6~8 hours; 3R; 4R; 5S)-5-tert-butyl diphenyl siloxy-3-hydroxy-4-methyl-1-(methoxy acyl group) hexanaphthene 5; 5 in the presence of diethylazodicarboxylate and triphenylphosphine through Mitsunobu eliminate react (4S; 6S)-6-tert-butyl diphenyl siloxy-1-methyl-4-(methoxy acyl group) tetrahydrobenzene 6; 6 get (4S through 12~18 hours deprotection bases under the room temperature in the tetrahydrofuran solution of tetrabutylammonium; 6S)-6-hydroxyl-1-methyl-4-(methoxy acyl group) tetrahydrobenzene 7; 7 at room temperature reacted 8~12 hours with p-nitrobenzoic acid in the presence of diethylazodicarboxylate and triphenylphosphine; get (4S through the Mitsunobu configuration conversion; 6R)-1-methyl-6-p-nitrophenyl methanoyl-4-(methoxy acyl group) tetrahydrobenzene 8,8 is in anhydrous K
2CO
3Took off (the 4S that the p-nitrophenyl formyl radical gets configuration conversion in 6~9 hours with reacting under the room temperature in the dry methyl alcohol; 6R)-6-hydroxyl-1-methyl-4-(methoxy acyl group) tetrahydrobenzene 9; 9 through with Grignard reagent MeMgBr under-50~-78 ℃ of cold condition, react 5~9 hours optically pure trans-(+)-sobrerol 1, reactions steps is as follows:
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 03118136 CN1216023C (en) | 2003-03-05 | 2003-03-05 | Method for preparing trans-(+)-hydrated pinanol |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 03118136 CN1216023C (en) | 2003-03-05 | 2003-03-05 | Method for preparing trans-(+)-hydrated pinanol |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1435402A CN1435402A (en) | 2003-08-13 |
CN1216023C true CN1216023C (en) | 2005-08-24 |
Family
ID=27634384
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 03118136 Expired - Fee Related CN1216023C (en) | 2003-03-05 | 2003-03-05 | Method for preparing trans-(+)-hydrated pinanol |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN1216023C (en) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104311481A (en) * | 2014-09-24 | 2015-01-28 | 万特制药(海南)有限公司 | Method for preparing pitavastatin through configuration reversion of pitavastatin isomer |
CN108601755B (en) * | 2015-09-09 | 2021-08-10 | 韩国生命工学研究院 | Composition for preventing or treating myasthenia-related diseases comprising pinol hydrate |
-
2003
- 2003-03-05 CN CN 03118136 patent/CN1216023C/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
CN1435402A (en) | 2003-08-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN100593024C (en) | Process of synthesizing taxol and docetaxel | |
RU2335500C2 (en) | Method of production of mevalonic acid derivatives inhibiting hmg-coa reductase | |
US6858749B2 (en) | Synthesis of 3,6-dialkyl-5,6-dihydro-4-hydroxy-pyran-2-one | |
CN101402655B (en) | Process for producing platinum | |
CN109761984B (en) | Method for synthesizing chiral five-membered carbocyclic purine nucleoside by asymmetric hydrogen transfer | |
JP6054108B2 (en) | Process for producing optically active 2,3-dihydrofarnesal | |
CN112142660B (en) | Method for simply, conveniently and efficiently synthesizing 4-aryl butyric acid derivative | |
CN1216023C (en) | Method for preparing trans-(+)-hydrated pinanol | |
JP5622019B2 (en) | Asymmetric organic molecular catalyst having amino alcohol derivative salt structure and method for producing optically active compound using said asymmetric organic molecular catalyst | |
JPH04266880A (en) | Production of 3-dpa-lactone | |
CN107129515B (en) | Novel method for synthesizing natural product Cyanolide A analogue | |
JPH0665226A (en) | @(3754/24)3r,5s)-3,5,6-trihydroxyhexanoic acid derivative and its production | |
JP2010229097A (en) | New oxazolidine derivative, new oxazolidine derivative salt and method for producing optically active compound using the oxazolidine derivative salt as asymmetric organic molecular catalyst | |
CN109336845B (en) | Optically active cyclopentane-3-imine and its derivative and preparation method | |
EP2280007B1 (en) | The preparation method of (3s,4s)-3-hexyl-4-((r)-2-hydroxytridecyl)-oxetan-2-one and the product of that method | |
CN101153040A (en) | Method for synthesizing polyhydroxy pyrroline acridine alkaloid | |
JP2006089493A (en) | Optically active cobalt (ii) complex | |
CN112062743B (en) | Resveratrol derivative and application thereof | |
CN107253939B (en) | 3-benzyloxy-tetrahydropyran, preparation method thereof and preparation method of tetrahydropyran-3-cyclic alcohol with single configuration | |
CA2442934A1 (en) | Enantiomerically selective cyclopropanation | |
CN105399714B (en) | A kind of new method of asymmetric syntheses natural products () Euscapholide isomers | |
JPH0791223B2 (en) | Process for producing optically active 6-t-butoxy-3,5-dihydroxyhexanoic acid ester | |
JP2896612B2 (en) | Method for producing sphingosine and intermediates | |
CN105198722A (en) | Method for asymmetrically catalyzing and synthesizing (R)-4, 7-dimethyl-1-tetralone | |
JP2958665B2 (en) | Optically active 3,5-anti-dihydroxycarboxylic acid ester derivative |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C19 | Lapse of patent right due to non-payment of the annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |