CN108315370A - A kind of preparation method of halogen tryptophan - Google Patents
A kind of preparation method of halogen tryptophan Download PDFInfo
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Abstract
The present invention relates to a kind of preparation method of halogen tryptophan, the shortcomings of raw material is dangerous in current method, condition is harsh, step is long, unsuitable amplification is mainly solved.The technical scheme is that：A kind of preparation method of halogen tryptophan, includes the following steps：Halogen indoles occurs Mannich reaction with formaldehyde and dimethylamine and generates halogen donaxine; halogen donaxine, which is reacted with acetamino diethyl malonate under sodium ethoxide catalysis, generates intermediate dibasic acid esters; intermediate dibasic acid esters hydrolyzes under alkaline case obtains acetyl group halogen tryptophan, and acetyl group halogen tryptophan, which is enzymatically split, obtains halogen tryptophan.The product of the present invention, is widely used in medical research, or even all uses important function in the synthesis of certain native compounds.
Description
Technical field
The present invention relates to a kind of preparation methods of tryptophan derivative, the especially preparation method of halogen tryptophan.
Background technology
The amphotericity and static characteristic showed because of indole ring synthesizes field, color ammonia in proteins and peptides
Acid is an important component units.Optical voidness, non-natural tryptophan derivative cause larger interest in synthesis field, not only
Only it is the transformation because to its primary structure, also as its own is in a variety of natural materials（Such as indoles lactams V, ergotic acid,
Ergot alkaloid）It is highly useful intermediate in building-up process.Indole ring substituted tryptophan derivative can be used as potential
Senescence inhibitor, outer at adjuster, the component part of antitumor and anticancer agent.Halogen tryptophan is one type.Through consulting literatures,
It is more novel there are three types of synthetic method, simply it is described below：
1, tetrahedron notification（2008 , vol. 49, # 17 p. 2795 – 2798）It is described, halogen indoles and Serine
Dehydration occurs in aceticanhydride and acetic acid, generates acetyl group-halogen tryptophan, acetyl group-halogen tryptophan enzymatically hydrolyzes
Halogen tryptophan can be obtained.This reaction route is simple, ingenious in design, but verified, and first step reaction impurities are more, need layer
Analysis column can just take the preferable acetyl group of purity-halogen tryptophan, be unfavorable for amplifying production on a large scale.
2, tetrahedron notification（2015 , vol. 56, # 43 art. No. 46689, p. 5882 – 5885）Institute
It states, is alkylated with chiral glycine enol form equivalent to prepare halogen tryptophan by halogen donaxine quaternary ammonium salt, step is long,
Condition is harsh（It is related to -78 DEG C of ultralow temperature reactions）, it is also not suitable for industrialization needs.
3, journal of biological chemistry（ 2016 , vol. 291, # 38 p. 20068 – 20084）It is described, halogen indoles
Through two-step reaction to halogen donaxine quaternary ammonium salt, diphenyl methylene glycine ethyl ester reacted with sodium hydrogen after again with halogen donaxine season
Ammonium salt reaction can obtain diphenyl protection halogen tryptophan ethyl ester, this intermediate can obtain halogen through being deprotected and hydrolyzing two-step reaction
Tryptophan.The method equally exists step length, the problem of condition harshness, and reagent is again dangerous.
Invention content
The object of the present invention is to provide a kind of preparation methods of halogen tryptophan, mainly solve the original in existing synthetic method
The problems such as material is dangerous, condition is harsh, step is long.
The technical scheme is that：A kind of preparation method of halogen tryptophan, includes the following steps：Halogen indoles and first
Mannich occurs for aldehyde and dimethylamine（Mannich）Reaction generates halogen donaxine, halogen donaxine and acetylamino malonic acid two
Ethyl ester reaction under sodium ethoxide catalysis generates intermediate dibasic acid esters, and intermediate dibasic acid esters hydrolyzes under alkaline case and obtains acetyl group halogen
Tryptophan, acetyl group halogen tryptophan, which is enzymatically split, obtains halogen tryptophan.
Concrete operation step is the first step, and mass percentage concentration is 30% dimethylamine solution and mass percentage concentration is 40%
Formalin is added in there-necked flask, cools to -5 DEG C -5 DEG C, and glacial acetic acid is added dropwise, is added dropwise, halogen indoles is added portionwise, adds
After complete, it is slowly raised to room temperature reaction 4 hours, reaction solution is poured into the sodium hydroxide solution of 2mol/L, is stirred overnight, filtered,
Solid is collected, drying obtains halogen donaxine.Second step, the ethyl alcohol that acetamino diethyl malonate is added to sodium ethoxide are molten
In liquid, halogen donaxine is added in stirring and dissolving, and stirring and dissolving keeps reaction system to be in 0-20 DEG C, and dimethyl suflfate is added dropwise,
It is added dropwise, is slowly raised to room temperature reaction 20 hours, pours into a large amount of water, be positioned in refrigerator, it is overnight, it filters, drying obtains
Intermediate dibasic acid esters.Third walks, and intermediate dibasic acid esters is added in the sodium hydroxide solution that mass percentage concentration is 10%, leads to nitrogen and protects
Ethyl alcohol is added in shield, and T=70 DEG C reaction boils off whole ethyl alcohol to terminating, and water and ethyl acetate is added, and layering discards oil phase, retains
Water phase, water phase are acidified with the hydrochloric acid of 3mol/L, and a large amount of solids are precipitated, overnight, are filtered, and drying obtains acetyl group halogen tryptophan.
4th step, acetyl group halogen tryptophan are suspended in pure water, and 2mol/L sodium hydroxide solutions are added, and adjust pH=7, and second is added
Acylase reacts at room temperature 3 days, boils off most of water, and solid is precipitated, is stirred overnight, and filters, and drying obtains halogen tryptophan.Instead
Answer formula as follows：
The halogen indoles is in 5- fluoro indoles, 5- chloro-indoles, 5- bromo indoles, 6- fluoro indoles, 6- chloro-indoles or 6- bromo indoles
It is a kind of.
The acetylase is L- acetylases or D- acetylases.
The halogen tryptophan is L-5- fluorotryptophans, D-5- fluorotryptophans, L-5- chlorine tryptophan, D-5- chlorine color ammonia
Acid, L-5- bromines tryptophan, D-5- bromines tryptophan, L-6- fluorotryptophans, D-6- fluorotryptophans, L-6- chlorine tryptophan, D-6- chlorine colors
One kind in propylhomoserin, L-6- bromines tryptophan or D-6- bromine tryptophans.
The beneficial effects of the invention are as follows：Reaction condition of the present invention is mild, and reaction route is simple, and use is all conventional examination
Agent, for yield up to 72-82%, conventional certain methods are that intermediate dibasic acid esters direct hydrolysis is generated to the tryptophan of mixed, Huo Zhetong
The product that expensive chiral reagent splits into single configuration is crossed, all not economic enough the timeliness of these methods, the invention avoids these
Disadvantage.
Description of the drawings
Fig. 1 is the nuclear magnetic resonance spectroscopy of 1 product of the embodiment of the present invention.
Fig. 2 is the infared spectrum of 1 product of the embodiment of the present invention.
Fig. 3 is the nuclear magnetic resonance spectroscopy of 2 product of the embodiment of the present invention.
Fig. 4 is the infared spectrum of 2 product of the embodiment of the present invention.
Fig. 5 is the nuclear magnetic resonance spectroscopy of 3 product of the embodiment of the present invention.
Fig. 6 is the infared spectrum of 3 product of the embodiment of the present invention.
Fig. 7 is the nuclear magnetic resonance spectroscopy of 4 product of the embodiment of the present invention.
Fig. 8 is the infared spectrum of 4 product of the embodiment of the present invention.
Fig. 9 is the nuclear magnetic resonance spectroscopy of 5 product of the embodiment of the present invention.
Figure 10 is the infared spectrum of 5 product of the embodiment of the present invention.
Figure 11 is the nuclear magnetic resonance spectroscopy of 6 product of the embodiment of the present invention.
Figure 12 is the infared spectrum of 6 product of the embodiment of the present invention.
Specific implementation mode
Embodiment 1：
The first step, 1.1 equivalent quality percentage concentrations are 30% dimethylamine solution and 1 equivalent quality percentage concentration is 40% formalin
It is added in there-necked flask, cools to -5 DEG C -5 DEG C, the glacial acetic acid of 2.6 equivalents is added dropwise, is added dropwise, 1 equivalent 5- fluorine is added portionwise
Indoles after adding, is slowly raised to room temperature reaction 4 hours, reaction solution is poured into the 2mol/L sodium hydroxide solutions of 10 times of equivalents,
It is stirred overnight, filters, collect solid, drying obtains 5- fluorine donaxines, yield 93%.Second step, the acetylamino of 1 equivalent the third two
Diethyl phthalate is added in sodium ethoxide/ethanol solution of equivalent, stirring and dissolving, and the 5- fluorine donaxines of equivalent are added, stirring
Dissolving keeps reaction system to be in 0-20 DEG C, and 2 equiv. sulfuric acid dimethyl esters are added dropwise, are added dropwise, and it is small to be slowly raised to room temperature reaction 20
When, it pours into the water of 10 times of all raw material weights, is positioned in refrigerator, it is overnight, it filters, drying obtains 5- fluorine intermediate doubles
Ester, yield 92%.Third walks, and 5- fluorine intermediate dibasic acid esters is added to the sodium hydroxide solution that 2.5 equivalent quality percentage concentrations are 10%
In, lead to nitrogen protection, is added and reacts 6 hours with the isometric ethyl alcohol of sodium hydroxide solution, T=70 DEG C, boil off whole ethyl alcohol, add
Entering water and ethyl acetate, be layered, discard oil phase, retains water phase, water phase is acidified with the hydrochloric acid of 3mol/L, and a large amount of solids are precipitated, every
Night filters, and drying obtains acetyl group -5- fluorotryptophans, yield 67%.4th step, acetyl group -5- fluorotryptophans are suspended in 30 times
In the pure water of volume, 2mol/L sodium hydroxide solutions are added dropwise, adjust pH=7, the L- of 1% weight of acetyl group 5- fluorotryptophans is added
Acetylase reacts at room temperature 3 days, boils off most of water, and solid is precipitated, is stirred overnight at room temperature, and filters, and drying obtains L-5- fluorine
Tryptophan, yield 80%.The nuclear magnetic resonance spectroscopy of product and infrared see Fig. 1 and Fig. 2.
Embodiment 2：
The first step, 1.1 equivalent quality percentage concentrations are 30% dimethylamine solution and 1 equivalent quality percentage concentration is 40% formalin
It is added in there-necked flask, cools to -5 DEG C -5 DEG C, the glacial acetic acid of 2.6 equivalents is added dropwise, is added dropwise, 1 equivalent 5- fluorine is added portionwise
Indoles after adding, is slowly raised to room temperature reaction 4 hours, reaction solution is poured into the 2mol/L sodium hydroxide solutions of 10 times of equivalents,
It is stirred overnight, filters, collect solid, drying obtains 5- fluorine donaxines, yield 93%.Second step, the acetylamino of 1 equivalent the third two
Diethyl phthalate is added in sodium ethoxide/ethanol solution of equivalent, stirring and dissolving, and the 5- fluorine donaxines of equivalent are added, stirring
Dissolving keeps reaction system to be in 0-20 DEG C, and 2 equiv. sulfuric acid dimethyl esters are added dropwise, are added dropwise, and it is small to be slowly raised to room temperature reaction 20
When, it pours into the water of 10 times of all raw material weights, is positioned in refrigerator, it is overnight, it filters, drying obtains 5- fluorine intermediate doubles
Ester, yield 92%.Third walks, and 5- fluorine intermediate dibasic acid esters is added to the sodium hydroxide solution that 2.5 equivalent quality percentage concentrations are 10%
In, lead to nitrogen protection, is added and reacts 6 hours with the isometric ethyl alcohol of sodium hydroxide solution, T=70 DEG C, boil off whole ethyl alcohol, add
Entering water and ethyl acetate, be layered, discard oil phase, retains water phase, water phase is acidified with the hydrochloric acid of 3mol/L, and a large amount of solids are precipitated, every
Night filters, and drying obtains acetyl group -5- fluorotryptophans, yield 67%.4th step, acetyl group -5- fluorotryptophans are suspended in 30 times
In the pure water of volume, 2mol/L sodium hydroxide solutions are added dropwise, adjust pH=7, the D- of 1% weight of acetyl group 5- fluorotryptophans is added
Acetylase reacts at room temperature 3 days, boils off most of water, and solid is precipitated, is stirred overnight at room temperature, and filters, and drying obtains D-5- fluorine
Tryptophan, yield 72%.The nuclear magnetic resonance spectroscopy of product and infrared see Fig. 3 and Fig. 4.
Embodiment 3：
The first step, 1.1 equivalent quality percentage concentrations are 30% dimethylamine solution and 1 equivalent quality percentage concentration is 40% formalin
It is added in there-necked flask, cools to -5 DEG C -5 DEG C, the glacial acetic acid of 2.6 equivalents is added dropwise, is added dropwise, 1 equivalent 6- bromines is added portionwise
Indoles after adding, is slowly raised to room temperature reaction 4 hours, reaction solution is poured into the 2mol/L sodium hydroxide solutions of 10 times of equivalents,
It is stirred overnight, filters, collect solid, drying obtains 6- bromine donaxines, yield 89%.Second step, the acetylamino of 1 equivalent the third two
Diethyl phthalate is added in sodium ethoxide/ethanol solution of equivalent, stirring and dissolving, and the 6- bromine donaxines of equivalent are added, stirring
Dissolving keeps reaction system to be in 0-20 DEG C, and 2 equiv. sulfuric acid dimethyl esters are added dropwise, are added dropwise, and it is small to be slowly raised to room temperature reaction 20
When, it pours into the water of 10 times of all raw material weights, is positioned in refrigerator, it is overnight, it filters, drying obtains 6- bromine intermediate doubles
Ester, yield 85%.Third walks, and 6- bromine intermediate dibasic acid esters is added to the sodium hydroxide solution that 2.5 equivalent quality percentage concentrations are 10%
In, lead to nitrogen protection, is added and reacts 5 hours with the isometric ethyl alcohol of sodium hydroxide solution, T=70 DEG C, boil off whole ethyl alcohol, add
Entering water and ethyl acetate, be layered, discard oil phase, retains water phase, water phase is acidified with the hydrochloric acid of 3mol/L, and a large amount of solids are precipitated, every
Night filters, and drying obtains acetyl group -6- bromine tryptophans, yield 72%.4th step, acetyl group -6- bromine tryptophans are suspended in 30 times
In the pure water of volume, 2mol/L sodium hydroxide solutions are added dropwise, adjust pH=7, the L- of 1% weight of acetyl group 6- bromines tryptophan is added
Acetylase reacts at room temperature 3 days, boils off most of water, and solid is precipitated, is stirred overnight at room temperature, and filters, and drying obtains L-6- bromines
Tryptophan, yield 82%.The nuclear magnetic resonance spectroscopy of product and infrared see Fig. 5 and Fig. 6.
Embodiment 4：
The first step, 1.1 equivalent quality percentage concentrations are 30% dimethylamine solution and 1 equivalent quality percentage concentration is 40% formalin
It is added in there-necked flask, cools to -5 DEG C -5 DEG C, the glacial acetic acid of 2.6 equivalents is added dropwise, is added dropwise, 1 equivalent 6- chlorine is added portionwise
Indoles after adding, is slowly raised to room temperature reaction 4 hours, reaction solution is poured into the 2mol/L sodium hydroxide solutions of 10 times of equivalents,
It is stirred overnight, filters, collect solid, drying obtains 6- chlorine donaxines, yield 95%.Second step, the acetylamino of 1 equivalent the third two
Diethyl phthalate is added in sodium ethoxide/ethanol solution of equivalent, stirring and dissolving, and the 6- chlorine donaxines of equivalent are added, stirring
Dissolving keeps reaction system to be in 0-20 DEG C, and 2 equiv. sulfuric acid dimethyl esters are added dropwise, are added dropwise, and it is small to be slowly raised to room temperature reaction 20
When, it pours into the water of 10 times of all raw material weights, is positioned in refrigerator, it is overnight, it filters, it is double to obtain 6- chloromethylated intermediates for drying
Ester, yield 92%.Third walks, and 6- chloromethylated intermediate dibasic acid esters is added to the sodium hydroxide solution that 2.5 equivalent quality percentage concentrations are 10%
In, lead to nitrogen protection, is added and reacts 5 hours with the isometric ethyl alcohol of sodium hydroxide solution, T=70 DEG C, boil off whole ethyl alcohol, add
Entering water and ethyl acetate, be layered, discard oil phase, retains water phase, water phase is acidified with the hydrochloric acid of 3mol/L, and a large amount of solids are precipitated, every
Night filters, and drying obtains acetyl group -6- chlorine tryptophans, yield 75%.4th step, acetyl group -6- chlorine tryptophans are suspended in 30 times
In the pure water of volume, 2mol/L sodium hydroxide solutions are added dropwise, adjust pH=7, the L- of 1% weight of acetyl group 6- chlorine tryptophan is added
Acetylase reacts at room temperature 3 days, boils off most of water, and solid is precipitated, is stirred overnight at room temperature, and filters, and drying obtains L-6- chlorine
Tryptophan, yield 79%.The nuclear magnetic resonance spectroscopy of product and infrared see Fig. 7 and Fig. 8.
Embodiment 5：
The first step, 1.1 equivalent quality percentage concentrations are 30% dimethylamine solution and 1 equivalent quality percentage concentration is 40% formalin
It is added in there-necked flask, cools to -5 DEG C -5 DEG C, the glacial acetic acid of 2.6 equivalents is added dropwise, is added dropwise, 1 equivalent 6- chlorine is added portionwise
Indoles after adding, is slowly raised to room temperature reaction 4 hours, reaction solution is poured into the 2mol/L sodium hydroxide solutions of 10 times of equivalents,
It is stirred overnight, filters, collect solid, drying obtains 6- chlorine donaxines, yield 95%.Second step, the acetylamino of 1 equivalent the third two
Diethyl phthalate is added in sodium ethoxide/ethanol solution of equivalent, stirring and dissolving, and the 6- chlorine donaxines of equivalent are added, stirring
Dissolving keeps reaction system to be in 0-20 DEG C, and 2 equiv. sulfuric acid dimethyl esters are added dropwise, are added dropwise, and it is small to be slowly raised to room temperature reaction 20
When, it pours into the water of 10 times of all raw material weights, is positioned in refrigerator, it is overnight, it filters, it is double to obtain 6- chloromethylated intermediates for drying
Ester, yield 92%.Third walks, and 6- chloromethylated intermediate dibasic acid esters is added to the sodium hydroxide solution that 2.5 equivalent quality percentage concentrations are 10%
In, lead to nitrogen protection, is added and reacts 5 hours with the isometric ethyl alcohol of sodium hydroxide solution, T=70 DEG C, boil off whole ethyl alcohol, add
Entering water and ethyl acetate, be layered, discard oil phase, retains water phase, water phase is acidified with the hydrochloric acid of 3mol/L, and a large amount of solids are precipitated, every
Night filters, and drying obtains acetyl group -6- chlorine tryptophans, yield 75%.4th step, acetyl group -6- chlorine tryptophans are suspended in 30 times
In the pure water of volume, 2mol/L sodium hydroxide solutions are added dropwise, adjust pH=7, the D- of 1% weight of acetyl group 6- chlorine tryptophan is added
Acetylase reacts at room temperature 3 days, boils off most of water, and solid is precipitated, is stirred overnight at room temperature, and filters, and drying obtains D-6- chlorine
Tryptophan, yield 81%.The nuclear magnetic resonance spectroscopy of product and infrared see Fig. 9 and Figure 10.
Embodiment 6：
The first step, 1.1 equivalent quality percentage concentrations are 30% dimethylamine solution and 1 equivalent quality percentage concentration is 40% formalin
It is added in there-necked flask, cools to -5 DEG C -5 DEG C, the glacial acetic acid of 2.6 equivalents is added dropwise, is added dropwise, 1 equivalent 6- fluorine is added portionwise
Indoles after adding, is slowly raised to room temperature reaction 4 hours, reaction solution is poured into the 2mol/L sodium hydroxide solutions of 10 times of equivalents,
It is stirred overnight, filters, collect solid, drying obtains 6- fluorine donaxines, yield 78%.Second step, the acetylamino of 1 equivalent the third two
Diethyl phthalate is added in sodium ethoxide/ethanol solution of equivalent, stirring and dissolving, and the 6- fluorine donaxines of equivalent are added, stirring
Dissolving keeps reaction system to be in 0-20 DEG C, and 2 equiv. sulfuric acid dimethyl esters are added dropwise, are added dropwise, and it is small to be slowly raised to room temperature reaction 20
When, it pours into the water of 10 times of all raw material weights, is positioned in refrigerator, it is overnight, it filters, drying obtains 6- fluorine intermediate doubles
Ester, yield 93%.Third walks, and 6- fluorine intermediate dibasic acid esters is added to the sodium hydroxide solution that 2.5 equivalent quality percentage concentrations are 10%
In, lead to nitrogen protection, is added and reacts 5 hours with the isometric ethyl alcohol of sodium hydroxide solution, T=70 DEG C, boil off whole ethyl alcohol, add
Entering water and ethyl acetate, be layered, discard oil phase, retains water phase, water phase is acidified with the hydrochloric acid of 3mol/L, and a large amount of solids are precipitated, every
Night filters, and drying obtains acetyl group -6- fluorotryptophans, yield 70%.4th step, acetyl group -6- fluorotryptophans are suspended in 30 times
In the pure water of volume, 2mol/L sodium hydroxide solutions are added dropwise, adjust pH=7, the L- of 1% weight of acetyl group 6- fluorotryptophans is added
Acetylase reacts at room temperature 3 days, boils off most of water, and solid is precipitated, is stirred overnight at room temperature, and filters, and drying obtains L-6- fluorine
Tryptophan, yield 81%.The nuclear magnetic resonance spectroscopy of product and infrared see Figure 11 and Figure 12.
Claims (7)
1. a kind of preparation method of halogen tryptophan, includes the following steps：With formaldehyde and dimethylamine Mannich occurs for halogen indoles
Reaction generates halogen donaxine, halogen donaxine and acetamino diethyl malonate and is reacted among generation under sodium ethoxide catalysis
Body dibasic acid esters, it is characterised in that：Intermediate dibasic acid esters hydrolyzes under alkaline condition obtains acetyl group halogen tryptophan, acetyl group halogen color
Propylhomoserin enzymatically splits and obtains halogen tryptophan.
2. a kind of preparation method of halogen tryptophan according to claim 1, specific preparation process are as follows：The first step, matter
Amount percentage concentration is 30% dimethylamine solution and mass percentage concentration is that 40% formalin is added in there-necked flask, cools to -5
DEG C -5 DEG C, glacial acetic acid is added dropwise, is added dropwise, halogen indoles is added portionwise, after adding, is slowly raised to room temperature reaction 4 hours, it will be anti-
It answers liquid to pour into the sodium hydroxide solution of 2mol/L, is stirred overnight, filter, collect solid, drying obtains halogen donaxine；The
Two steps, acetamino diethyl malonate are added in the ethanol solution of sodium ethoxide, stirring and dissolving, and halogen donaxine is added, stirs
Dissolving is mixed, reaction system is kept to be in 0-20 DEG C, dimethyl suflfate is added dropwise, is added dropwise, is slowly raised to room temperature reaction 20 hours,
It pours into a large amount of water, is positioned in refrigerator, it is overnight, it filters, drying obtains intermediate dibasic acid esters；It is characterized in that：Third walks, in
Mesosome dibasic acid esters is added in sodium hydroxide solution, leads to nitrogen protection, and ethyl alcohol is added, and T=70 DEG C reaction boils off whole second to terminating
Water and ethyl acetate is added in alcohol, and layering discards oil phase, retains water phase, and water phase is acidified with hydrochloric acid, and solid is precipitated, overnight, filtering,
Drying, obtains acetyl group halogen tryptophan；4th step, acetyl group halogen tryptophan are suspended in pure water, and sodium hydroxide is added
Solution adjusts pH=7, and acetylase is added, and room temperature reaction boils off moisture content, and solid is precipitated, is stirred overnight, and filters, and drying obtains
Halogen tryptophan.
3. a kind of preparation method of halogen tryptophan according to claim 1 or 2, it is characterised in that：The halogen indoles
For one kind in 5- fluoro indoles, 5- chloro-indoles, 5- bromo indoles, 6- fluoro indoles, 6- chloro-indoles or 6- bromo indoles.
4. a kind of preparation method of halogen tryptophan according to claim 1 or 2, it is characterised in that：The acetylation
Enzyme is L- acetylases or D- acetylases.
5. a kind of preparation method of halogen tryptophan according to claim 1 or 2, it is characterised in that：The halogen color
Propylhomoserin is L-5- fluorotryptophans, D-5- fluorotryptophans, L-5- chlorine tryptophan, D-5- chlorine tryptophan, L-5- bromines tryptophan, D-5- bromines
Tryptophan, L-6- fluorotryptophans, D-6- fluorotryptophans, L-6- chlorine tryptophan, D-6- chlorine tryptophan, L-6- bromines tryptophan or D-6-
One kind in bromine tryptophan.
6. a kind of preparation method of halogen tryptophan according to claim 2, it is characterised in that：It is molten that third walks sodium hydroxide
Liquid mass percentage concentration is 10%, and the hydrochloric acid molar concentration is 3mol/L.
7. a kind of preparation method of halogen tryptophan according to claim 2, it is characterised in that：4th step sodium hydroxide is molten
Liquid molar concentration is 2mol/L, and the reaction time is 3 days.
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