CN116606237A - Synthesis method of tryptophan derivative - Google Patents
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- CN116606237A CN116606237A CN202310583465.3A CN202310583465A CN116606237A CN 116606237 A CN116606237 A CN 116606237A CN 202310583465 A CN202310583465 A CN 202310583465A CN 116606237 A CN116606237 A CN 116606237A
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- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical class C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 title claims abstract description 18
- 238000001308 synthesis method Methods 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 16
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 11
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 48
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
- -1 p-methoxybenzyl Chemical group 0.000 claims description 10
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical group [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 10
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 7
- 239000012267 brine Substances 0.000 claims description 7
- 238000004440 column chromatography Methods 0.000 claims description 7
- 239000011630 iodine Substances 0.000 claims description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- UGZBFCCHLUWCQI-LURJTMIESA-N methyl (2r)-3-iodo-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)[C@H](CI)NC(=O)OC(C)(C)C UGZBFCCHLUWCQI-LURJTMIESA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 238000005406 washing Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 229910052763 palladium Inorganic materials 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- UGZBFCCHLUWCQI-ZCFIWIBFSA-N methyl (2s)-3-iodo-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)[C@@H](CI)NC(=O)OC(C)(C)C UGZBFCCHLUWCQI-ZCFIWIBFSA-N 0.000 claims description 3
- PTXVSDKCUJCCLC-UHFFFAOYSA-N 1-hydroxyindole Chemical compound C1=CC=C2N(O)C=CC2=C1 PTXVSDKCUJCCLC-UHFFFAOYSA-N 0.000 claims description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 2
- 229940011051 isopropyl acetate Drugs 0.000 claims description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 238000005580 one pot reaction Methods 0.000 abstract 1
- 239000012074 organic phase Substances 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000012295 chemical reaction liquid Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000006073 displacement reaction Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 2
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
- PSUMJUDAKYMCRW-UHFFFAOYSA-N 3-chloro-5-methoxy-1h-indole Chemical compound COC1=CC=C2NC=C(Cl)C2=C1 PSUMJUDAKYMCRW-UHFFFAOYSA-N 0.000 description 1
- KAZWWBYOCSMDMA-UHFFFAOYSA-N 5-benzyl-1,3-dihydroindol-2-one Chemical compound C=1C=C2NC(=O)CC2=CC=1CC1=CC=CC=C1 KAZWWBYOCSMDMA-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003667 tyrosine derivatives Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention relates to a synthesis method of tryptophan derivatives, which mainly solves the technical problems of more steps and low efficiency of the existing synthesis method. The technical scheme of the invention is as follows: a method for synthesizing a tryptophan derivative, the reaction formula being as follows:
Description
Technical Field
The invention relates to a method for quickly and simply synthesizing tryptophan derivatives. The reaction route reported in the literature is shortened from 3 steps of reaction to 1 step of reaction, and the synthesis efficiency is improved.
Background
Tryptophan is an essential amino acid for human body, plays an important role in metabolism, growth and development of life, and is widely applied to industries such as food, feed, medicine, chemical industry and the like. Tryptophan derivatives are also widely used in the biomedical field. Document j. Med. Chem.2013, 56, 19, 7651-7668 and patent WO2015/48306,2015, a1 report a method for synthesizing tyrosine derivatives, specifically as follows:
in the related report, the synthesis of the target product can be completed by 3 steps of reactions, and the efficiency is low.
Disclosure of Invention
The invention aims to provide a rapid, simple and convenient synthesis method of tryptophan derivatives, which mainly solves the technical problems of more synthesis steps and low efficiency of the existing synthesis method. The method has the characteristics of simple and convenient operation and easy industrial production.
The technical scheme of the invention is as follows: a method for synthesizing tryptophan derivatives, comprising the steps of: adding organic solvent into a reaction container, starting stirring, and sequentially adding zinc powder, iodine and N 2 3 times of replacement, adding 3-X-5-R oxyindole, adding (R) -methyl 2-tert-butoxycarbonylamino-3-iodopropionate or (S) -methyl 2-tert-butoxycarbonylamino-3-iodopropionate, and metal palladium catalyst N 2 3 times of replacement, stirring and reacting completely, extracting, washing with brine, and purifying by column chromatography to obtain the target product. The reaction formula is as follows:
or (b)
Wherein: r is alkyl or aryl; the alkyl is methyl, ethyl, n-propyl, isopropyl, tert-butyl, C5-C10 straight-chain or branched-chain alkyl, preferably one of methyl, ethyl, n-propyl, isopropyl, tert-butyl or n-hexyl; the aryl is benzyl, phenyl and a group with substituent groups on a benzene ring, and is preferably one of benzyl, phenyl or p-methoxybenzyl; x is a halogen atom selected from: cl, br or I.
The organic solvent is selected from one or more of the following: ethyl acetate, dichloromethane, tetrahydrofuran, 2-methyl, methyl acetate, ethyl formate, isopropyl acetate, t-butyl acetate, methyl t-butyl ether, diethyl ether, toluene, DMF. Preferably one of DMF, ethyl acetate, tetrahydrofuran or toluene.
The metal palladium catalyst is tetra (triphenylphosphine) palladium or Pd 2 (dba) 3 。
The reaction temperature is 0 to 100℃and preferably 40 to 80 ℃.
The invention has the beneficial effects that: the invention provides a rapid, simple and convenient synthesis method of tryptophan derivatives. The reaction route reported in the literature is shortened from 3 steps to 1 step, and the synthesis efficiency is improved.
Detailed Description
The invention will be further illustrated with reference to specific embodiments, to which the invention is not limited.
Example 1
Into a 150mL reaction flask, DMF (20 mL) was added, stirring was turned on, zinc powder (9.75 g,0.149 mol), iodine (3.78 g,14.9 mmol) and N were added sequentially 2 3-Bromo-5-benzyloxindole (16.5 g,0.0547 mol) in 30 ml DMF was added dropwise after 3-displacement, methyl (R) -2-tert-butoxycarbonylamino-3-iodopropionate (18.0 g 0.0497 mol), tetrakis (triphenylphosphine) palladium (1.72 g 1.49 mmol) N 2 3 times of replacement, heating to 50-60 ℃ and stirring for 12h, completely reacting, pouring the reaction liquid into 100 mL water, extracting with 200 mL ethyl acetate, washing an organic phase once with brine, removing the solvent from the organic phase, and purifying by column chromatography (200-300 mesh silica gel, petroleum ether/ethyl acetate volume ratio=10:1 mobile phase) to obtain a 17.5 g target product. The yield thereof was found to be 83%, 1 H NMR（CDCl 3 , 400 MHz, ppm）: 10.73（br, 1H）6.90-7.50 (m, 10H), 5.10 (s, 2H), 4.68 (t,1H), 3.65 (s, 3H), 3.17-3.42 (dd, 2H), 1.40 ( s, 9H)。
example 2
150 Into a mL reactor, tetrahydrofuran (20) and mL were added, stirring was turned on, zinc powder (9.75 g,0.149 mol), iodine (3.78 g,14.9 mmol) and N were added sequentially 2 3-bromine-containing solution is added dropwise after 3 times of replacementA solution of 5-benzyloxindole (16.5 g,0.0547 mol) in 30 ml tetrahydrofuran was added, after dropwise addition, to methyl (S) -2-tert-butoxycarbonylamino-3-iodopropionate (18.0 g 0.0497 mol), tetrakis (triphenylphosphine) palladium (1.72 g 1.49 mmol) N 2 3 times of replacement, heating to 40-50 ℃, stirring for 12 hours, completely reacting, pouring the reaction liquid into 100 mL water, extracting with 200 mL ethyl acetate, washing an organic phase once with brine, removing the solvent from the organic phase, and purifying by column chromatography (200-300 mesh silica gel, petroleum ether/ethyl acetate volume ratio=10:1 mobile phase) to obtain a 16.9 g target product. The yield was 80%, 1 H NMR（CDCl 3 , 400 MHz, ppm）: 10.73（br, 1H）6.91-7.50 (m, 10H), 5.12 (s, 2H), 4.68 (t,1H), 3.64 (s, 3H), 3.18-3.43 (dd, 2H), 1.41 ( s, 9H)。
example 3
150 In a mL reactor, ethyl acetate (20. 20 mL) was added and stirring was turned on, followed by zinc powder (9.75 g,0.149 mol), iodine (3.78 g,14.9 mmol), N 2 3-Bromo-5-p-methoxybenzyloxyindole (18.2 g,0.0547 mol) in ethyl acetate 30 ml was added dropwise after 3-displacement, methyl (R) -2-t-butoxycarbonylamino-3-iodopropionate (18.0 g, 0.0497 mol), tetrakis (triphenylphosphine) palladium (1.72 g, 1.49 mmol) N was added 2 3 times of replacement, heating to 60-70 ℃ and stirring for 12h, completely reacting, pouring the reaction liquid into 100 mL water, extracting with 200 mL ethyl acetate, washing an organic phase once with brine, removing the solvent from the organic phase, and purifying by column chromatography (200-300 mesh silica gel, petroleum ether/ethyl acetate volume ratio=10:1 mobile phase) to obtain a 15.8 g target product. The yield was 70%, 1 H NMR（CDCl 3 , 400 MHz, ppm）: 10.73（br, 1H），6.79-7.40 (m, 9H), 5.14 (s, 2H), 4.68 (t,1H), 3.81 (s, 3H), 3.66 (s, 3H), 3.17-3.43 (dd, 2H), 1.42 ( s, 9H)。
example 4
150 Into a mL reactor, toluene (20. 20 mL) was added, stirring was turned on, zinc powder (9.75 g,0.149 mol), iodine (3.78 g,14.9 mmol) and N were added sequentially 2 3-chloro-5-methoxyindole (10 g,0.0547 mol) in 30 ml toluene was added dropwise after 3-displacement, methyl (R) -2-t-butoxycarbonylamino-3-iodopropionate (18.0 g, 0.0497 mol), tetrakis (triphenylphosphine) palladium (1.72 g, 1.49 mmol) N was added 2 3 times of replacement, heating to 70-80 ℃ and stirring for 12 hours, completely reacting, pouring the reaction liquid into 100 mL water, extracting with 200 mL ethyl acetate, washing an organic phase once with brine, removing the solvent from the organic phase, and purifying by column chromatography (200-300 mesh silica gel, petroleum ether/ethyl acetate volume ratio=10:1 mobile phase) to obtain the 11.2 g target product. The yield thereof was found to be 65%, 1 H NMR（CDCl 3 , 400 MHz, ppm）: 10.73（br, 1H），7.00-7.40 (m, 5H), 4.68 (t,1H), 3.82 (s, 3H), 3.65 (s, 3H), 3.17-3.42 (dd, 2H), 1.42 ( s, 9H)。
example 5
150 In a mL reactor, DMF (20 mL) was added and stirring was turned on, zinc powder (9.75 g,0.149 mol), iodine (3.78 g,14.9 mmol) and N were added sequentially 2 3-iodo-5-ethoxyindole (15.7 g,0.0547 mol) was added dropwise in 30 ml DMF, after which (R) -methyl 2-t-butoxycarbonylamino-3-iodopropionate (18.0 g, 0.0497 mol), sphos (1.02 g, 2.49 mmol) and Pd2 (dba) 3 (1.36 g, 1.49 mmol) were added, N2 was replaced 3 times, the reaction was stirred for 12h at 50-60℃until complete, the reaction was poured into 100 mL water, extracted with 200 mL ethyl acetate, the organic phase was washed once with brine, the solvent was removed from the organic phase, and the product was purified by column chromatography (200-300 mesh silica gel, petroleum ether/ethyl acetate volume ratio=10:1 mobile phase) to give 12.2 g of the target product. The yield thereof was found to be 68%, 1 H NMR（CDCl 3 , 400 MHz, ppm）: 10.73（br, 1H），7.00-7.40 (m, 5H), 4.68 (t,1H), 3.82 (s, 3H), 3.65 (s, 3H), 3.17-3.42 (dd, 2H), 1.42 ( s, 9H)，1.34 ( t, 3H)。
example 6
The specific operation was the same as in example 1, using 3-bromo-5-isopropoxyindole, yield 70%, 1 H NMR（CDCl 3 , 400 MHz, ppm）: 10.73（br, 1H）6.80-7.39 (m, 5H), 4.68 (m, 2H), 3.66 (s, 3H), 3.17-3.42 (dd, 2H), 1.42 ( s, 9H), 1.29 ( d, 6H)。
example 7
The procedure is as in example 1, using 3-bromo-5-tert-butoxyindole, in a yield of 65%, 1 H NMR（CDCl 3 , 400 MHz, ppm）: 10.73（br, 1H）6.80-7.39 (m, 5H), 4.68 (m, 1H), 3.66 (s, 3H), 3.17-3.42 (dd, 2H), 1.42 ( s, 9H), 1.40 ( s, 9H)。
example 8
The specific procedure was as in example 2, using 3-bromo-5-n-hexyloxindole, yield 75%, 1 H NMR（CDCl 3 , 400 MHz, ppm）: 10.73（br, 1H）6.80-7.39 (m, 5H), 4.68 (m, 1H), 4.06 (t, 2H), 3.66 (s, 3H), 3.17-3.42 (dd, 2H), 1.80 ( m, 2H), 1.47(m, 6H), 1.42 ( s, 9H), 0.88 ( t, 3H)。
example 9
The specific operation was the same as in example 5, using 3-bromo-5-phenoxyindole, yield 80%, 1 H NMR（CDCl 3 , 400 MHz, ppm）: 10.73（br, 1H），6.83-7.42 (m, 10H), 4.68 (m, 1H), 3.66 (s, 3H), 3.17-3.42 (dd, 2H), 1.42 ( s, 9H)。
Claims (8)
1. a synthesis method of tryptophan derivatives is characterized in that: the method comprises the following steps: adding organic solvent into a reaction container, starting stirring, and sequentially adding zinc powder, iodine and N 2 3 times of replacement, adding 3-X-5-R oxyindole, adding (R) -methyl 2-tert-butoxycarbonylamino-3-iodopropionate or (S) -methyl 2-tert-butoxycarbonylamino-3-iodopropionate, and metal palladium catalyst N 2 3 times of replacement, stirring and reacting completely, extracting, washing with brine, and purifying by column chromatography to obtain a target product, wherein the reaction formula is as follows:or->The method comprises the steps of carrying out a first treatment on the surface of the Wherein: r is alkyl or aryl; x is a halogen atom selected from: cl, br or I.
2. The method for synthesizing a tryptophan derivative according to claim 1, wherein: the alkyl is one of methyl, ethyl, n-propyl, isopropyl, tert-butyl and C5-C10 straight-chain or branched-chain alkyl; the aryl is one of benzyl, phenyl and a group with substituent on a benzene ring.
3. The method for synthesizing a tryptophan derivative according to claim 2, wherein: the alkyl is one of methyl, ethyl, n-propyl, isopropyl, tert-butyl or n-hexyl; the aryl is one of benzyl, phenyl or p-methoxybenzyl.
4. The method for synthesizing a tryptophan derivative according to claim 1, wherein: the organic solvent is selected from one or more of the following: ethyl acetate, dichloromethane, tetrahydrofuran, 2-methyltetrahydrofuran, methyl acetate, ethyl formate, isopropyl acetate, t-butyl acetate, methyl t-butyl ether, diethyl ether, toluene, DMF.
5. The method for synthesizing a tryptophan derivative according to claim 4, wherein: the organic solvent is selected from one of DMF, ethyl acetate, tetrahydrofuran or toluene.
6. The method for synthesizing a tryptophan derivative according to claim 1, wherein: the metal palladium catalyst is tetra (triphenylphosphine) palladium or Pd 2 (dba) 3 。
7. The method for synthesizing a tryptophan derivative according to claim 1, wherein: the reaction temperature is 0-100 ℃.
8. The method for synthesizing a tryptophan derivative according to claim 7, wherein: the reaction temperature is 40-80 ℃.
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