CN114560803B - Synthesis method of 5-hydroxytryptophan - Google Patents
Synthesis method of 5-hydroxytryptophan Download PDFInfo
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- CN114560803B CN114560803B CN202210326363.9A CN202210326363A CN114560803B CN 114560803 B CN114560803 B CN 114560803B CN 202210326363 A CN202210326363 A CN 202210326363A CN 114560803 B CN114560803 B CN 114560803B
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- hydroxytryptophan
- tryptophan
- hydrogen peroxide
- ascorbic acid
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- 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
Abstract
The invention discloses a method for synthesizing 5-hydroxytryptophan in a mild aqueous solution reaction system, and belongs to the technical field of chemical synthesis methods. The invention takes L-tryptophan, hydrogen peroxide and ascorbic acid as raw materials and nano Fe 3 O 4 As a catalyst, oxidation-reduction reaction is carried out in an aqueous solution system to generate 5-hydroxytryptophan. The raw materials for synthesizing the 5-hydroxytryptophan are biological endogenous compounds, and nano Fe is taken as a catalyst 3 O 4 Has excellent biocompatibility, can meet the synthesis conditions under physiological environment, and is expected to be suitable for biological application of 5-hydroxytryptophan.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis methods, and particularly relates to a synthesis method of 5-hydroxytryptophan.
Background
5-hydroxytryptophan is a special amino acid present in plants and animals and is widely used in foods and medicines. The 5-hydroxytryptophan can increase the concentration of serotonin and the melatonin level in the brain, improve spinal atrophy symptoms, promote sleep and has good therapeutic effect on depression. Exogenous 5-hydroxytryptophan is usually supplemented orally, and can cross the blood brain barrier, increase the concentration of 5-hydroxytryptamine in the brain, reduce the production of cytokines in vivo, and thus improve depression. Endogenous 5-hydroxytryptophan is produced mainly by hydroxylation of endogenous L-tryptophan by tryptophan hydroxylases, a process which is often degenerated to cause neurological diseases.
In the current synthetic route for 5-hydroxytryptophan, a common method is a biological enzyme method or a multi-step condensation chemical synthesis method using 3-methylphenol as a raw material. In which the bioenzyme method requires a large amount of bacterial cells or lysate, and the multi-step condensation chemical synthesis method requires multiple condensation reactions, hydrogenation reactions, hydrolysis reactions, etc., all compared with the prior artIs more complicated. The invention takes the L-tryptophan which is cheap and easy to obtain as the reaction raw material, the ascorbic acid and the hydrogen peroxide as the redox agent, and the commercialized nano Fe 3 O 4 The synthesis of 5-hydroxytryptophan is realized as a catalyst in a mild aqueous system in one step. The reaction process is simple and convenient, the reaction raw materials are green in color temperature and mild, and a complex post-treatment process is not needed. Therefore, the invention is expected to provide more practical technical support for large-scale synthesis of 5-hydroxytryptophan. In addition, as all components in the reaction system have good biocompatibility, the method can provide a potential technical basis for biological application of the 5-hydroxytryptophan.
Disclosure of Invention
The invention aims to provide a synthesis method of 5-hydroxytryptophan, which adopts a simple one-step reaction chemical synthesis route, adopts L-tryptophan as a reaction raw material, adopts hydrogen peroxide and ascorbic acid as an oxidant and a reducing agent respectively, and adopts nano Fe 3 O 4 As a catalyst, the 5-hydroxytryptophan is synthesized by reaction in a mild aqueous solution system at room temperature. Wherein, hydrogen peroxide is in nano Fe 3 O 4 To provide hydroxyl radicals for the reaction, ascorbic acid converts the hydroxyl radicals to hydroxyl peroxide radicals, and finally converts L-tryptophan to 5-hydroxytryptophan. Neither hydrogen peroxide nor ascorbic acid alone can cause this reaction to occur.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a synthesis method of 5-hydroxytryptophan comprises the following steps:
a. dissolving L-tryptophan in a dilute hydrochloric acid solution;
b. hydrogen peroxide, ascorbic acid and nano Fe 3 O 4 Respectively dissolving or dispersing in water;
c. adding hydrogen peroxide solution, ascorbic acid solution and nano Fe into L-tryptophan solution 3 O 4 A suspension;
d. after the shaking reaction at room temperature, the formation of 5-hydroxytryptophan was detected.
The mass ratio of the L-tryptophan to the dilute hydrochloric acid solution used in the step a is 10 -5 :1~10 -3 1, the concentration of the dilute hydrochloric acid solution is 10 -4 M。
The mass ratio of hydrogen peroxide to water used in the step b is 10 -3 :1~10 -1 1, the mass ratio of the ascorbic acid to the water is 10 -2 1-1:1, nano Fe 3 O 4 The mass ratio of the water to the water is 10 -3 :1~10 -2 :1。
The molar ratio of hydrogen peroxide to L-tryptophan used in the step c is 1:1-1000:1, the molar ratio of ascorbic acid to L-tryptophan is 1:1-1000:1, and nanometer Fe is prepared by the following steps 3 O 4 The mass ratio of the L-tryptophan to the L-tryptophan is 10 -1 1-10:1; the nanometer Fe 3 O 4 Can be any commercially available nano Fe with the grain diameter of 5-500 nm 3 O 4 。
And d, the reaction time in the step is 1-60 minutes.
The invention has the beneficial effects that:
the invention provides a novel preparation method of 5-hydroxytryptophan, which only needs one-step reaction, has mild reaction conditions and simple post-treatment, and can be used as a large-scale industrialized synthesis method of 5-hydroxytryptophan.
Drawings
FIG. 1 is a mass spectrometric qualitative detection of 5-hydroxytryptophan synthesized as described in the examples;
FIG. 2 is a mass spectrometry quantitative determination result of 5-hydroxytryptophan synthesized in accordance with the example;
FIG. 3 is a mass spectrometry quantitative detection result of a sample operated according to comparative example 1;
FIG. 4 is a mass spectrometry quantitative detection result of a sample operated according to comparative example 2.
Detailed Description
A synthesis method of 5-hydroxytryptophan comprises the following steps:
a. dissolving L-tryptophan in a diluted hydrochloric acid solution, wherein the mass ratio of the L-tryptophan to the diluted hydrochloric acid solution is 10 -5 :1~10 -3 :1；
b. Hydrogen peroxide is added toAscorbic acid, nano Fe 3 O 4 Respectively dissolving or dispersing in water, wherein the mass ratio of hydrogen peroxide to water is 10 -3 :1~10 -1 1, the mass ratio of the ascorbic acid to the water is 10 -2 1-1:1, nano Fe 3 O 4 The mass ratio of the water to the water is 10 -3 :1~10 -2 :1；
c. Adding hydrogen peroxide solution, ascorbic acid solution and nano Fe into L-tryptophan solution 3 O 4 The molar ratio of hydrogen peroxide to L-tryptophan is 1:1-1000:1, the molar ratio of ascorbic acid to L-tryptophan is 1:1-1000:1, and nanometer Fe is used for preparing the suspension 3 O 4 The mass ratio of the L-tryptophan to the L-tryptophan is 10 -1 1-10:1; the nanometer Fe 3 O 4 Can be any commercially available nano Fe with the grain diameter of 5-500 nm 3 O 4 ；
d. After the oscillation reaction at room temperature, the generation of 5-hydroxytryptophan can be detected, and the reaction time is 1-60 minutes.
In order to make the contents of the present invention more easily understood, the technical scheme of the present invention will be further described with reference to the specific embodiments, but the present invention is not limited thereto.
Examples
A synthesis method of 5-hydroxytryptophan comprises the following steps:
a. into the reaction vessel were charged 4.4. 4.4 mg (0.02 mmol) of L-tryptophan and 10 mL of 10 -4 M dilute hydrochloric acid solution is stirred and dissolved to obtain L-tryptophan solution of 2 mM;
b. adding 0.5 mL of 30wt% hydrogen peroxide solution into 9.5 of mL water, and uniformly mixing to obtain 500 mM hydrogen peroxide solution; adding 880.6 mg ascorbic acid into 10 mL water, and uniformly mixing to obtain 500 mM ascorbic acid solution; 10 mg nanometer Fe with particle size of 20 nm 3 O 4 Adding into 10 mL water, mixing to obtain 1 mg/mL nanometer Fe 3 O 4 A suspension;
c. to 10 mL of 2 mM L-tryptophan solution were added 2 mL of 500 mM hydrogen peroxide solution, 2 mL of 500 mM ascorbic acid solution, 2 mL of 1 mg/mL nano Fe 3 O 4 A suspension;
d. after the reaction was carried out at room temperature for 10 minutes with shaking, the formation of 5-hydroxytryptophan was detected.
FIG. 1 shows the results of qualitative detection of 5-hydroxytryptophan synthesized in accordance with the examples, and FIG. 2 shows the results of quantitative detection of 5-hydroxytryptophan synthesized in accordance with the examples. The mass spectrum detection result is consistent with the standard substance, and the content change of 5-hydroxytryptophan before and after the reaction is obvious, which indicates that the method can generate 5-hydroxytryptophan in a physiological environment.
Comparative example 1
In the synthesis method of 5-hydroxytryptophan disclosed by the invention, hydrogen peroxide plays a role in providing hydroxyl radicals for reaction. The reaction cannot proceed without the addition of hydrogen peroxide.
As comparative example 1 to which hydrogen peroxide was not added, the following steps were included:
a. into the reaction vessel were charged 4.4. 4.4 mg (0.02 mmol) of L-tryptophan and 10 mL of 10 -4 M dilute hydrochloric acid solution is stirred and dissolved to obtain L-tryptophan solution of 2 mM;
b. adding 880.6 mg ascorbic acid into 10 mL water, and uniformly mixing to obtain 500 mM ascorbic acid solution; 10 mg nanometer Fe with particle size of 20 nm 3 O 4 Adding into 10 mL water, mixing to obtain 1 mg/mL nanometer Fe 3 O 4 A suspension;
c. to 10 mL of 2 mM L-tryptophan solution, 2 mL of 500 mM ascorbic acid solution, 2 mL of 1 mg/mL nano Fe was added 3 O 4 A suspension;
d. after 60 minutes of shaking reaction at room temperature, the formation of 5-hydroxytryptophan could not be detected.
FIG. 3 is the result of mass spectrometry quantitative detection of a sample operated in comparative example 1. The absence of a peak of 5-hydroxytryptophan in the mass spectrum indicates that comparative example 1, without hydrogen peroxide, cannot produce 5-hydroxytryptophan.
Comparative example 2
In the synthesis method of 5-hydroxytryptophan disclosed by the invention, ascorbic acid plays a role in converting hydroxyl radicals into hydroxyl peroxide radicals. The reaction was not allowed to proceed without the addition of ascorbic acid.
As comparative example 2 without addition of ascorbic acid, the following steps were included:
a. into the reaction vessel were charged 4.4. 4.4 mg (0.02 mmol) of L-tryptophan and 10 mL of 10 -4 M dilute hydrochloric acid solution is stirred and dissolved to obtain L-tryptophan solution of 2 mM;
b. adding 0.5 mL of 30wt% hydrogen peroxide solution into 9.5 of mL water, and uniformly mixing to obtain 500 mM hydrogen peroxide solution; 10 mg nanometer Fe with particle size of 20 nm 3 O 4 Adding into 10 mL water, mixing to obtain 1 mg/mL nanometer Fe 3 O 4 A suspension;
c. to 10 mL of 2 mM L-tryptophan solution, 2 mL of 500 mM hydrogen peroxide solution and 2 mL of 1 mg/mL nano Fe were added 3 O 4 A suspension;
d. after 60 minutes of shaking reaction at room temperature, the formation of 5-hydroxytryptophan could not be detected.
FIG. 4 is a mass spectrometry quantitative detection result of a sample operated according to comparative example 2. The absence of a peak of 5-hydroxytryptophan in the mass spectrum indicates that comparative example 2, without addition of ascorbic acid, cannot produce 5-hydroxytryptophan.
The foregoing description is only of the preferred embodiments of the invention, and all changes and modifications that come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Claims (7)
1. A synthesis method of 5-hydroxytryptophan is characterized in that: the method comprises the following steps:
a. dissolving L-tryptophan in a dilute hydrochloric acid solution;
b. hydrogen peroxide, ascorbic acid and nano Fe 3 O 4 Respectively dissolving or dispersing in water;
c. adding hydrogen peroxide solution, ascorbic acid solution and nano Fe into L-tryptophan solution 3 O 4 A suspension;
d. after the shaking reaction at room temperature, 5-hydroxytryptophan was obtained.
2. The method for synthesizing 5-hydroxytryptophan according to claim 1, wherein: the mass ratio of the L-tryptophan to the dilute hydrochloric acid solution used in the step a is 10 -5 :1~10 -3 :1。
3. The method for synthesizing 5-hydroxytryptophan according to claim 1, wherein: the mass ratio of hydrogen peroxide to water used in step b was 10 -3 :1~10 -1 1, the mass ratio of the ascorbic acid to the water is 10 -2 1-1:1, nano Fe 3 O 4 The mass ratio of the water to the water is 10 -3 :1~10 -2 :1。
4. The method for synthesizing 5-hydroxytryptophan according to claim 1, wherein: the molar ratio of hydrogen peroxide to L-tryptophan used in the step c is 1:1-1000:1, the molar ratio of ascorbic acid to L-tryptophan is 1:1-1000:1, and nanometer Fe is prepared by the following steps 3 O 4 The mass ratio of the L-tryptophan to the L-tryptophan is 10 -1 :1~10:1。
5. The method for synthesizing 5-hydroxytryptophan according to claim 1, wherein: the nanometer Fe 3 O 4 The particle size of the particles is 5-500 nm.
6. The method for synthesizing 5-hydroxytryptophan according to claim 1, wherein: the concentration of the dilute hydrochloric acid solution is 10 -4 M。
7. The method for synthesizing 5-hydroxytryptophan according to claim 1, wherein: and d, the reaction time is 1-60 minutes.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1344682A (en) * | 1970-09-25 | 1974-01-23 | Vyzk Ustav Organ Syntez | Process for producing dl/tryptophane |
| CH614702A5 (en) * | 1975-04-08 | 1979-12-14 | Made Labor Sa | Process for the preparation of 5-hydroxytryptophan glutamate |
| CN102351775A (en) * | 2011-09-14 | 2012-02-15 | 佛山普正医药科技有限公司 | Preparation method of levo-5-hydroxytryptophan |
| CN110128603A (en) * | 2019-06-11 | 2019-08-16 | 云南建投高分子材料有限公司 | Stablize the method for synthesis polycarboxylate water-reducer under cryogenic conditions |
-
2022
- 2022-03-30 CN CN202210326363.9A patent/CN114560803B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1344682A (en) * | 1970-09-25 | 1974-01-23 | Vyzk Ustav Organ Syntez | Process for producing dl/tryptophane |
| CH614702A5 (en) * | 1975-04-08 | 1979-12-14 | Made Labor Sa | Process for the preparation of 5-hydroxytryptophan glutamate |
| CN102351775A (en) * | 2011-09-14 | 2012-02-15 | 佛山普正医药科技有限公司 | Preparation method of levo-5-hydroxytryptophan |
| CN110128603A (en) * | 2019-06-11 | 2019-08-16 | 云南建投高分子材料有限公司 | Stablize the method for synthesis polycarboxylate water-reducer under cryogenic conditions |
Non-Patent Citations (1)
| Title |
|---|
| Unusual Acetylation-Dependent Reaction Cascade in the Biosynthesis of the Pyrroloindole Drug Physostigmine;Joyce Liu等;《Angew. Chem. Int. Ed.》;第1-5页 * |
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