CN102838639A - Synthetic method of N-aryl-D-glucosamine - Google Patents
Synthetic method of N-aryl-D-glucosamine Download PDFInfo
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Abstract
The invention provides a synthetic method of N-aryl-D-glucosamine, comprising the steps of using 1,3,4,6-O-4-benzyl-D-glucosamine hydrochloride as a raw material to synthesize 1,3,4,6-O-4-benzyl-N-aryl-D-glucosamine through C-N cross-coupling reaction under catalysis of copper, and then performing debenzylation to synthesize N-aryl-D-glucosamine. According to the invention, different aryl iodides can be used to synthesize different substituted N-aryl-D-glucosamine, and the method is universal and has high efficiency; and copper which is easily accessible and cheap is used as catalyst, the condition is mild, the yield is high and the method has good application prospect.
Description
Technical field
The present invention relates to the organic synthesis field, relate in particular to the compound method of N-aryl-D-glucosamine.
Background technology
D-glucosamine (D-Glucosamine) be with crab, shrimp, shell body be raw material through the monose that processing makes, have the synthetic isoreactivity of treatment of arthritis, anti-inflammatory, SP polysaccharide.Contain reactive group amino in the D-glucosamine molecular structure, carry out chemically modified and can obtain different verivates.These modification reactions not only help structure activity study, and in molecule, introduce other group, will find the material that biological activity is stronger.Because the mutual intersection and the infiltration of each subject in recent years makes the chemical modification method of D-glucosamine constantly expand.
At present, the chemically modified in D-glucosamine N site lays particular emphasis on acidifying, acidylate, alkylation, and N-arylation verivate seldom obtains.Up to now, there is two routine N-arylations-D-glucosamine verivate to obtain synthetic ((a) Harton, D.
J. Org. Chem. 1964, 29, 1776. (b) Jung, M. E.; Dong, T. A.; Cai, X.-L.
Tetrahedron Lett. 2011,
52, 2533.), shown in the following chemical formula:
Use simple nucleophilic substitution synthesizing aryl verivate in the aforesaid method, aromatic yl reagent-ing need be haled electronics base nitro, is difficult to carry out otherwise react, and the method universality is poor, the substrate narrow application range.Therefore, seek that a kind of wide spectrum is suitable for synthetic N-aryl-the D-glucosamine thereof, derivatives thereof is very important.
Summary of the invention
The compound method that the purpose of this invention is to provide a kind of N-aryl-D-glucosamine verivate, with 1,3,4,6-O-tetrabenzyl-D-glucosamine is a raw material, obtains N-aryl-D-glucosamine.
For reaching the foregoing invention purpose, the present invention proposes the compound method of N-aryl-D-glucosamine verivate, and its synthesis path is as follows:
The compound method of N-aryl provided by the invention-D-glucosamine verivate comprises following steps:
S1. with formula (
α) shown in 1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride, formula (
β) shown in aryl iodide, cesium carbonate, cuprous salt and 2-acetyl cyclohexanone be dissolved among the DMF, in 120-130 ℃ of following stirring reaction 8-20 hour, postcooling was accomplished in reaction under protection of nitrogen gas; The ether dilution is filtered, and takes out and desolvates; The silica gel chromatography dilution obtains intermediate product, formula (
γ) shown in 1,3,4,6-O-tetrabenzyl-N-aryl-D-glucosamine;
S2. the intermediate product that step S1 is obtained, formula (
γ) shown in 1,3,4,6-O-tetrabenzyl-N-aryl-D-glucosamine is dissolved in methyl alcohol and the ETHYLE ACETATE mixed solvent, adds trichoroacetic acid(TCA) and palladium carbon, feeding H
2, stirred 30-48 hour down in 40 ℃, filter, methanol wash is taken out and is desolvated, silica gel chromatography, finally obtain formula (
δ) shown in N-aryl ammonia-D-base glucose.
In the compound method of above-mentioned N-aryl-D-glucosamine verivate, formula (
β) shown in aryl iodide in R be 3 or the 4-substituting group, substituting group is H, alkyl, alkoxyl group, halogen, COOR1, wherein R1 is an alkyl.
Among the step S1 of aforesaid method, the consumption molar ratio of α (1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride) and aryl iodide is n (α): n (aryl iodide)=1.0: 2.0 – 1.0: 3.0.
Among the step S1 of aforesaid method, cuprous salt is CuI, CuBr, CuCl.The consumption molar ratio of α (1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride) and cuprous salt is n (α): n (cuprous salt)=1.0: 0.1 – 1.0: 0.2.
Among the step S1 of aforesaid method, the consumption molar ratio of α (1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride) and 2-acetyl cyclohexanone is n (α): n (2-acetyl pimelinketone)=1.0: 0.2 – 1.0: 0.4.
Among the step S1 of aforesaid method, 1,3,4 shown in the formula (α), the consumption molar ratio of 6-O-tetrabenzyl-D-glucosamine hydrochloride and cesium carbonate is 1.0: 2.5 – 1.0: 3.0.
Among the step S1 of aforesaid method, α (1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride) is n (α): V (DMF)=1.0mmol with the usage ratio of DMF: 0.5mL – 1.0mmol: 0.6mL.
Among the step S2 of aforesaid method, intermediate product β and trichoroacetic acid(TCA) molar ratio are n (β): n (trichoroacetic acid(TCA))=1.0: 1.0 – 1.0: 1.1.
Embodiment
To help to understand the present invention through following examples of implementation, but and limit content of the present invention.
1,1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride synthetic
(1eq. 100mmol) is dissolved in aqueous sodium hydroxide solution (1eq., the 100mmol of 100mL with the 21.5gD-glucosamine hydrochloride; C=1mol/L), under the vigorous stirring, drip the aubepine (1eq. of 12.1mL in the room temperature; 100mmol), continue to stir 2h, termination reaction.Decompress filter, the washing (2 * 20mL), ether wash (2 * 20mL), vacuum-drying 12h, crude product
2, productive rate 70%.
With 1.48g exsiccant compound
2(1eq., 50mmol), (5eq. 250mmol) is dissolved among the 200mL exsiccant DMF 30mL benzyl bromine, ice-water bath cooling.Under the vigorous stirring, add 10.0g sodium hydride (57%-63% oil content looses, and 250mmol divides 10 equal portions to add).System returns to room temperature, continues to stir 12h, in system, drips 40mL ETHYLE ACETATE termination reaction.Rotary Evaporators revolves dried, and the ether dilution is washed once, the dried over mgso organic layer, and Rotary Evaporators revolves dried, gets crude product
3Silica gel (sherwood oil: triethylamine=100mL:1mL soaks) column chromatography purification (eluent: sherwood oil: ETHYLE ACETATE: triethylamine=25mL: 100mL: 1mL), get yellow oily compound 3, productive rate 85%.
With compound
3Be dissolved in the acetone (50mL), add 10mL hydrochloric acid soln (5N), backflow 30min is cooled to room temperature, suction filtration solid, acetone wash (2 * 10mL), compound
αThe methanol aqueous solution recrystallization gets white needle-like crystals, productive rate 75%.m.p.?138℃-140℃,?
1H?NMR?(400?MHz,?DMSO)?δ?8.41?(s,?br,?3H),?7.46?(dd,?J?=?8.1,?1.4?Hz,?2H),?7.41?–?7.25?(m,?16H),?7.19?–?7.13?(m,?2H),?4.89?–?4.77?(m,?4H),?4.69?(d,?J?=?11.7?Hz,?1H),?4.65?(d,?J?=?11.0?Hz,?1H),?4.59?–?4.51?(m,?3H),?3.87?(dd,?J?=?10.3,?8.6?Hz,?1H),?3.76?–?3.56?(m,?4H),?3.09?–?3.02?(m,?1H).?IR?(KBr)?n:?3551,?3474,?3414,?3029,?2923,?1638,?1617,?1499,?1105,?1069,?618。
2,1,3,4,6-O-tetrabenzyl-N-aryl-D-glucosamine synthetic
2.1 1,3,4, the preparation of 6-O-tetrabenzyl-N-phenyl-D-glucosamine
In the Schlenk reaction tubes, add 288mg 1,3,4, and 6-O-tetrabenzyl-D-glucosamine hydrochloride (1eq., 0.5mmol); The 19mg cuprous iodide (20mol%, 0.10mmol) (3eq. 1.5mmol), vacuumizes with the 490mg cesium carbonate; Adding 168uL iodobenzene under the logical nitrogen (3eq., 1.5mmol), the 26uL2-acetyl cyclohexanone (40mol%, 0.20mmol); 0.25mL N, dinethylformamide, the sealed reaction system stirs 16h in 130 ℃ of oil baths.Cooling adds the dilution of 20mL ether, filters, and takes out and desolvates, silica gel column chromatography (ETHYLE ACETATE: the purifying of sherwood oil=1:8), productive rate: 81%.m.p.?114
oC-117
oC.?
1H?NMR?(400?MHz,?DMSO)?δ?7.40?–?7.27?(m,?8H),?7.25?–?7.14?(m,?10H),?7.11?–?7.03?(m,?4H),?6.74?(d,?J?=?7.8?Hz,?2H),?6.54?(t,?J?=?7.0?Hz,?1H),?5.62?(d,?J?=?9.0?Hz,?1H),?4.81?–?4.71?(m,?3H),?4.65?(d,?J?=?10.8?Hz,?1H),?4.61?–?4.51?(m,?4H),?4.48?(d,?J?=?7.9?Hz,?1H),?3.76?–?3.63?(m,?3H),?3.59?–?3.51?(m,?2H),?3.47?–?3.37?(m,?1H).?
13C?NMR?(100?MHz,?DMSO)?δ?149.08,?138.50,?138.32,?138.28,?137.84,?128.64,?128.23,?128.20,?127.98,.127.97,?127.73,?127.70,?127.58,?127.52,?127.42,?127.28,?127.16,?127.01,?115.70,?112.78,?102.56,?84.17,?77.99,?74.13,?74.09,?73.91,?72.36,?70.04,?68.92,?59.66.?IR?(KBr)?
n:?3548,?3478,?3414,?1636,?1620,?1111,?1072,?620。
2.2 1,3,4, the preparation of 6-O-tetrabenzyl-N-(4-aminomethyl phenyl)-D-glucosamine
In the Schlenk reaction tubes, add 288mg 1,3,4, and 6-O-tetrabenzyl-D-glucosamine hydrochloride (1eq., 0.5mmol); 218mg to the methyl iodobenzene (2eq., 1.0mmol), the 19mg cuprous iodide (20mol%, 0.10mmol) with 490mg cesium carbonate (3eq.; 1.5mmol), vacuumize, and adding 26uL 2-acetyl cyclohexanone under the logical nitrogen (40mol%, 0.20mmol); 0.26mL N, dinethylformamide, the sealed reaction system stirs 12h in 120 ℃ of oil baths.Cooling adds the dilution of 20mL ether, filters, and takes out and desolvates, silica gel column chromatography (ETHYLE ACETATE: the purifying of sherwood oil=1:8), productive rate: 72%.m.p.?115
oC-116
oC.?
1H?NMR?(400?MHz,?DMSO)?δ?7.39?–?7.27?(m,?8H),?7.25?–?7.16?(m,?10H),?7.14?–?7.07?(m,?2H),?6.89?(d,?J?=?8.2?Hz,?2H),?6.67?(d,?J?=?8.4?Hz,?2H),?4.84?–?4.70?(m,?3H),?4.66?(d,?J?=?10.9?Hz,?1H),?4.62?–?4.51?(m,?4H),?4.48?(d,?J?=?8.0?Hz,?1H),?3.79?–?3.60?(m,?3H),?3.60?–?3.50?(m,?2H),?3.41?–?3.36?(m,?1H),?2.17?(s,?3H).?
13C?NMR?(100?MHz,?DMSO)?δ?146.85,?138.57,?138.33,?138.30,?137.87,?129.09,?128.23,?128.20,?127.97,?127.73,?127.69,?127.58,?127.51,?127.42,?127.28,?127.17,?127.03,?124.11,?113.00,?102.66,?84.19,?78.01,?74.09,?74.07,?73.91,?72.37,?70.05,?68.95,?60.17,?20.08.?IR?(KBr)?
n:?3548,?3477,?3417,?1636,?1617,?1565,?1415,?1123,?1111,?1069,?617。
2.3 1,3,4, the preparation of 6-O-tetrabenzyl-N-(4-p-methoxy-phenyl)-D-glucosamine
In the Schlenk reaction tubes, add 288mg 1,3,4, and 6-O-tetrabenzyl-D-glucosamine hydrochloride (1eq., 0.5mmol); 350mg 4-methoxyl group iodobenzene (3eq., 1.5mmol), (20mol% is 0.10mmol) with 456mg cesium carbonate (2.8eq. for the 10mg cuprous chloride; 1.4mmol), vacuumize, and adding 26uL 2-acetyl cyclohexanone under the logical nitrogen (40mol%, 0.20mmol); 0.27mL N, dinethylformamide, the sealed reaction system stirs 8h in 130 ℃ of oil baths.Cooling adds the dilution of 20mL ether, filters, and takes out and desolvates, silica gel column chromatography (ETHYLE ACETATE: the purifying of sherwood oil=1:6), productive rate: 59%.m.p.?107
oC-109
oC.?
1H?NMR?(400?MHz,?DMSO)?δ?7.40?–?7.15?(m,?18H),?7.15?–?7.09?(m,?2H),?6.70?(s,?4H),?4.83?–?4.64?(m,?4H),?4.62?–?4.50?(m,?4H),?4.47?(d,?J?=?8.0?Hz,?1H),?3.79?–?3.59?(m,?6H),?3.54?(d,?J?=?5.2?Hz,?2H),?3.29?(dd,?J?=?9.3,?8.2?Hz,?1H).?
13C?NMR?(100?MHz,?DMSO)?δ?150.77,?143.36,?138.60,?138.33,?138.30,?137.88,?128.24,?128.22,?128.00,?127.99,?127.72,?127.71,?127.60,?127.53,?127.43,?127.30,?127.19,?127.04,?114.38,?113.93,?102.79,?84.23,?78.03,?74.07,?73.90,?72.37,?70,09,?68.95,?60.84,?55.36.?IR?(KBr)?
n:?3548,?3474,?3417,?1637,?1618,?1562,?1516,?1451,?1244,?1116,?1070,?742,?694。
2.4 1,3,4, the preparation of 6-O-tetrabenzyl-N-(4-chloro-phenyl-)-D-glucosamine
In the Schlenk reaction tubes, add 288mg 1,3,4, and 6-O-tetrabenzyl-D-glucosamine hydrochloride (1eq., 0.5mmol); 238mg is to chloroiodobenzone (2eq., 1.0 mmol), and (10mol% is 0.05mmol) with 423mg cesium carbonate (2.6eq. for the 10mg cuprous iodide; 1.3mmol), vacuumize, and adding 13uL 2-acetyl cyclohexanone under the logical nitrogen (20mol%, 0.10mmol); 0.28mL N, dinethylformamide, the sealed reaction system stirs 14h in 125 ℃ of oil baths.Cooling adds the dilution of 20mL ether, filters, and takes out and desolvates, silica gel column chromatography (ETHYLE ACETATE: the purifying of sherwood oil=1:6), productive rate: 71%.m.p.?118
oC-120
oC.?
1H?NMR?(400?MHz,?DMSO)?δ?7.39?–?7.27?(m,?8H),?7.24?–?7.15?(m,?8H),?7.16?(dd,?J?=?7.0,?2.5?Hz,?2H),?7.12?–?7.05?(m,?4H),?6.74?(d,?J?=?8.9?Hz,?2H),?4.82?–?4.70?(m,?3H),?4.67?(d,?J?=?10.9?Hz,?1H),?4.60?–?4.52?(m,?4H),?4.47?(d,?J?=?8.1?Hz,?1H),?3.80?–?3.52?(m,?5H),?3.46?–?3.37?(m,?1H).?
13C?NMR?(100?MHz,?DMSO)?δ?148.07,?138.46,?138.32,?138.25,?137.78,?128.30,?128.24,?128.22,?128.00,?127.73,?127.67,?127.60,?127.55,?127.43,?127.34,?127.24,?127.01,?118.85,?114.15,?102.47,?84.01,?78.01,?74.18,?74.10,?73.95,?72.38,?70.11,?68.88,?59.64.?IR?(KBr)?
n:?3445,?3343,?3029,?2895,?2862,?1600,?1517,?1492,?1450,?1114,?1070,?995,?813,?749,?697。
2.5 1,3,4, the preparation of 6-O-tetrabenzyl-N-(4-ethoxy acyl group phenyl)-D-glucosamine
In the Schlenk reaction tubes, add 288mg 1,3,4, and 6-O-tetrabenzyl-D-glucosamine hydrochloride (1eq., 0.5mmol); The 12mg cuprous bromide (20mol%, 0.10mmol) (2.5eq. 1.25mmol), vacuumizes with the 408mg cesium carbonate; Adding 250uL 4-Iodobenzoic acid ethyl ester under the logical nitrogen (3eq., 1.5mmol), 26uL 2-acetyl cyclohexanone (40mol%, 0.20mmol); 0.26mL N, dinethylformamide, the sealed reaction system stirs 15h in 130 ℃ of oil baths.Cooling adds the dilution of 20mL ether, filters, and takes out and desolvates, silica gel column chromatography (ETHYLE ACETATE: the purifying of sherwood oil=1:6), productive rate: 63%.m.p.?115
oC-116
oC.?
1H?NMR?(400?MHz,?DMSO)?δ?7.69?(d,?J?=?8.9?Hz,?2H),?7.40?–?7.26?(m,?8H),?7.22?–?7.14?(m,?10H),?7.06?(dd,?J?=?7.4,?2.1?Hz,?2H),?6.77?(d,?J?=?8.9?Hz,?2H),?4.84?–?4.63?(m,?4H),?4.62?–?4.47?(m,?5H),?4.22?(q,?J?=?7.1?Hz,?2H),?3.81?–?3.52?(m,?6H),?1.28?(t,?J?=?7.1?Hz,?3H).?
13C?NMR?(100?MHz,?DMSO)?δ?165.86,?153.15,?138.35,?138.31,?138.21,?137.72,?130.77,?128.25,?128.23,?128.01,?127.99,?127.76,?127.64,?127.61,?127.57,?127.44,?127.35,?127.26,?127.00,?116.33,?111.70,?102.04,?83.71,?77.96,?74.23,?74.14,?73.98,?72.39,?70.05,?68.84,?59.48,?58.69,?14.38.?IR?(KBr)?
n:?3468,?3420,?3353,?3029,?2900,?2866,?1700,?1610,?1537,?1274,?1175,?1111,?1069,?752,?694。
2.6 1,3,4, the preparation of 6-O-tetrabenzyl-N-(3-methoxy acyl group phenyl)-D-glucosamine
In the Schlenk reaction tubes, add 288mg 1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride (1eq.; 0.5mmol), the 15mg cuprous iodide (16mol%, 0.08mmol) with the 410mg cesium carbonate (2.5eq., 1.25mmol); Vacuumize, and adding 342mg m-iodobenzoic acid methyl esters under the logical nitrogen (2.6eq., 1.3mmol); 26uL 2-acetyl cyclohexanone (40mol%, 0.20mmol), the N of 0.3mL; Dinethylformamide, the sealed reaction system stirs 20h in 130 ℃ of oil baths.Cooling adds the dilution of 20mL ether, filters, and takes out and desolvates, silica gel column chromatography (ETHYLE ACETATE: the purifying of sherwood oil=1:6), productive rate: 54%.
1H?NMR?(400?MHz,?DMSO)?δ?7.42?–?7.25?(m,?10H),?7.23?–?7.12?(m,?11H),?7.12?–?7.06?(m,?2H),?7.02?–?6.95?(m,?1H),?4.85?–?4.64?(m,?4H),?4.62?–?4.46?(m,?5H),?3.86?–?3.50?(m,?9H),?3.44?(t,?J?=?8.7?Hz,?1H).?
13C?NMR?(100?MHz,?DMSO)?δ?166.86,?149.32,?138.48,?138.33,?138.27,?137.79,?130.11,?128.96,?128.28,?128.26,?128.02,?127.99,?127.77,?127.65,?127.59,?127.48,?127.36,?127.22,?126.93,?117.44,?116.59,?115.53,?113.09,?102.58,?83.78,?78.10,?74.27,?74.12,?73.99,?72.42,?70.17,?68.90,?59.61,?51.86.。
3, N-aryl-D-glucosamine is synthetic
3.1 N-phenyl-D-glucosamine is synthetic
With 308mg 1,3,4; (1eq. 0.5mmol) is dissolved in methyl alcohol and ETHYLE ACETATE (4mL+2mL) mixed solvent 6-O-tetrabenzyl-N-phenyl-D-glucosamine, adds 82mg trichoroacetic acid(TCA) (1eq.; 0.5mmol) and 100mg palladium carbon (10%Pd), be heated to 40 ℃, H
2Stirred in the atmosphere 30 hours, and filtered, methanol wash is taken out and is desolvated, silica gel column chromatography (trichloromethane: the purifying of methyl alcohol=8:1), productive rate: 76%.
1H?NMR?(400?MHz,?DMSO),?α?:?β?≈?2.7?:?1,?δ?7.06?(t,?J?=?7.5?Hz,?5.2H),?7.00?(t,?J?=?7.6?Hz,?2H),?6.78?–?6.65?(m,?7.8H),?6.56?(t,?J?=?6.7?Hz,?2.7H),?6.50?(t,?J?=?6.9?Hz,?1H),?5.00?(d,?J?=?2.8?Hz,?2.5H),?4.38?(d,?J?=?8.0?Hz,?1H),?3.82?–?3.41?(m,?40H),?3.24?–?3.10?(m,?4H).?IR?(KBr)?n:?IR?(KBr)?n:?3383,?2975,?2927,?2898,?1644,?1450,?1412,?1382,?1088,?1049,?880,?637。
3.2 N-(4-p-methoxy-phenyl)-D-glucosamine is synthetic
With 323mg 1,3,4; (1eq. 0.5mmol) is dissolved in methyl alcohol and ETHYLE ACETATE (4mL+2mL) mixed solvent 6-O-tetrabenzyl-N-(4-p-methoxy-phenyl)-D-glucosamine, adds 90mg trichoroacetic acid(TCA) (1.1eq.; 0.55mmol) and 100mg palladium carbon (10%Pd), be heated to 40 ℃, H
2Stirred in the atmosphere 48 hours, and filtered, methanol wash is taken out and is desolvated, silica gel column chromatography (trichloromethane: the purifying of methyl alcohol=8:1), productive rate: 87%.
1H?NMR?(400?MHz,?DMSO)?δ?α?:?β?≈?2.8?:?1,?7.36?(t,?J?=?11.1?Hz,?2H),?7.00?(d,?J?=?8.4?Hz,?2H),?4.74?(d,?J?=?2.7?Hz,?0.77H),?4.61?(d,?J?=?8.2?Hz,?0.27H),?4.03?–?3.19?(m,?14H).?IR?(KBr)?n:?3411,?2936,?2840,?1600,?1577,?1512,?1445,?1260,?1031,?759.。
In other proximate embodiment, also can adopt 1,3,4; 6-O-tetrabenzyl-N-(4-aminomethyl phenyl)-D-glucosamine, 1,3,4,6-O-tetrabenzyl-N-(4-chloro-phenyl-)-D-glucosamine, 1; 3,4,6-O-tetrabenzyl-N-(4-ethoxy acyl group phenyl)-D-glucosamine, 1,3; 4,6-O-tetrabenzyl-N-(3-methoxy acyl group phenyl)-D-glucosamine substitutes above-mentioned 1,3; 4,6-O-tetrabenzyl-N-phenyl-D-glucosamine carries out debenzylation, makes corresponding N-aryl-D-glucosamine.
Claims (8)
1. the compound method of a N-aryl-D-glucosamine comprises following steps:
S1. with formula (
α) shown in 1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride, formula (
β) shown in aryl iodide, cesium carbonate, cuprous salt and 2-acetyl cyclohexanone be dissolved among the DMF, in 120-130 ℃ of following stirring reaction 8-20 hour, postcooling was accomplished in reaction under protection of nitrogen gas; The ether dilution is filtered, and takes out and desolvates; The silica gel chromatography dilution obtains intermediate product, formula (
γ) shown in 1,3,4,6-O-tetrabenzyl-N-aryl-D-glucosamine;
S2. the intermediate product that step S1 is obtained, formula (
γ) shown in 1,3,4,6-O-tetrabenzyl-N-aryl-D-glucosamine is dissolved in methyl alcohol and the ETHYLE ACETATE mixed solvent, adds trichoroacetic acid(TCA) and palladium carbon, feeding H
2, stirred 30-48 hour down in 40 ℃, filter, methanol wash is taken out and is desolvated, silica gel chromatography, finally obtain formula (
δ) shown in N-aryl-D-glucosamine.
2. the compound method of N-aryl-D-glucosamine according to claim 1 is characterized in that, said R is 3 or 4-substituting group, and substituting group is H, alkyl, alkoxyl group, halogen, COOR
1, R wherein
1Be alkyl.
3. the compound method of N-aryl-D-glucosamine according to claim 1 is characterized in that, among the said step S1,
αThe consumption molar ratio of (1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride) and aryl iodide be n (
α): n (aryl iodide)=1.0: 2.0 – 1.0: 3.0.
4. the compound method of N-aryl-D-glucosamine according to claim 1 is characterized in that, among the said step S1, cuprous salt is CuI, CuBr, CuCl;
αThe consumption molar ratio of (1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride) and cuprous salt be n (
α): n (cuprous salt)=1.0: 0.1 – 1.0: 0.2.
5. the compound method of N-aryl-D-glucosamine according to claim 1 is characterized in that, among the said step S1,
αThe consumption molar ratio of (1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride) and 2-acetyl cyclohexanone be n (
α): n (2-acetyl pimelinketone)=1.0: 0.2 – 1.0: 0.4.
6. the compound method of N-aryl-D-glucosamine according to claim 1 is characterized in that, among the said step S1, formula (
α) shown in 1,3,4, the consumption molar ratio of 6-O-tetrabenzyl-D-glucosamine hydrochloride and cesium carbonate is 1.0: 2.5 – 1.0: 3.0.
7. the compound method of N-aryl-D-glucosamine according to claim 1 is characterized in that, among the said step S1,
αThe usage ratio of (1,3,4,6-O-tetrabenzyl-D-glucosamine hydrochloride) and solvent be n (
α): V (solvent)=1.0mmol: 0.5mL – 1.0mmol: 0.6mL.
8. the compound method of N-aryl-D-glucosamine according to claim 1 is characterized in that, among the said step S2, and intermediate product
βWith the trichoroacetic acid(TCA) molar ratio be n (
β): n (trichoroacetic acid(TCA))=1.0: 1.0 – 1.0: 1.1.
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| CN104961781A (en) * | 2015-06-04 | 2015-10-07 | 淮海工学院 | 2-deoxy-2-isorhodanate-1,3,4,6-tetra-O-benzyl-beta-D-glucopyranose, and synthetic method and application thereof |
| CN110407830A (en) * | 2019-08-21 | 2019-11-05 | 河南师范大学 | A method of synthesis N- aryl phenothiazine compound |
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| CN104961781B (en) * | 2015-06-04 | 2017-12-08 | 淮海工学院 | The O benzyls β D glucopyranoses of 2 deoxidation, 2 isothiocyanates 1,3,4,6 4 and synthetic method and purposes |
| CN110407830A (en) * | 2019-08-21 | 2019-11-05 | 河南师范大学 | A method of synthesis N- aryl phenothiazine compound |
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