CN114751801B - Method for preparing deuterated amino acid ester by photocatalysis - Google Patents
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- C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
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- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention discloses a method for preparing deuterated amino acid esters by photocatalysis, which is characterized in that amino acid esters are used as raw materials in deuterium water which is cheapest and easy to obtain, direct deuteration of the amino acid esters is realized under mild conditions by adopting multiple catalysts for concerted catalysis, and a target product deuterated amino acid ester compound is obtained.
Description
Technical Field
The invention belongs to the field of chemical synthesis, and particularly relates to a novel method for preparing deuterated amino acid ester through photocatalysis.
Background
Deuterium (D or D) isotope of hydrogen (H) 2 H) Also known as deuterium, consists of one proton, one neutron, and one electron. The abundance on the earth is 0.015%, and deuterium oxide D is mostly used 2 O is present in sea water. In chemistry, particularly in the field of pharmaceutical chemistry, research and synthesis of deuterated compounds have become one of the hot spots in current research. The C-D bond has higher bond energy compared with the C-H bond, so that more energy is required for breaking the C-D bond than for breaking the C-H bond, and the breaking of the C-H bond is the most important step in the metabolism process of the pharmaceutical compound, so that the rate of metabolism of the pharmaceutical compound can be reduced by using the deuterated compound containing the C-D bond. Compared with common drug molecules, the deuterated drug molecules have the following advantages: prolonging half-life period and blood concentration of the medicine, reducing dosage or frequency of medicine administration, blocking certain metabolic sites, reducing generation of toxic metabolites, reducing medicine toxicity, etc. At present, methods for preparing deuterated compounds mainly include methods such as hydrogen-deuterium exchange, direct deuteration and dehalogenation deuteration (J.Am.Chem.Soc.2019, 141,1467-1472, J.Am.Chem.Soc.2018,140,10970-10974, adv.Synth.Catal.2018,360, 637-641). Over the last 10 years, a group of companies focusing on deuteration research have had great success in the field of new drug development. Of these, the most famous abroad is Auspex (TEVA) and Concert. Auspex corporation established 2001, marketed in Nasdak, USA in 2014, with only 35 employees. Clinical three-stage test data of the star deuterated product SD-809 (deuterated tetrabenazine) under flag were published in 2015, and then TEVA company refused 32 hundred million dollars (with a premium rate of 42%) to be collected in capsules. In 2017, SD-809 is approved by FDA as the first deuterated drug worldwide for treating abnormal involuntary movement (HD) caused by Huntington's chorea, and is sold under the name of AUSTEDO TM . Compared with non-deuterated tetrabenazine, AUSTEDO can significantly slow down metabolic processes and has a half-life that is approximately 2 times that of non-deuterated tetrabenazine. Thus, by reducing the amount and frequency of administration, fewer adverse effects are experienced by the AUSTEDO, and the patient's tendency to become depressed and suicide is reduced, while the occurrence of withdrawal is suppressed. According to Evaluate Pharma, aucedo is expected to sell $ 6.67 billion in 2022.
Amino acid is a compound which is quite important in life science, and has great significance in the research of life chemistry. Deuterated amino acids are widely used for studying physiological mechanisms of animals, plants and microorganisms and physicochemical processes of cells in clinical medicine. Meanwhile, the deuterated amino acid is one of important means for researching the transfer, metabolism, action mechanism and toxic and side effects of the novel medicament in organisms. More importantly, the deuterated amino acid can be used for screening the newborn amino acid metabolic disorder. Currently, deuterated amino acids have the disadvantages of complicated steps, low deuteration rate, high cost and energy consumption, uncontrollable sites and the like (J.biol.chem, 1937,120,531-536, BBA-Gen Subject,1977,497,1-13, biochim BiophysActa,1976,446, 479-485). And/or the preparation of deuterated amino acid ester in the prior art often needs to prepare corresponding imidate (CN 113214099A, CN114436871A, CN111004076A, CN110885294A and the like) or dehydroamino acid ester (CN 113200895A, CN112358412A and the like) in advance, and then the preparation can be carried out under the condition of an expensive reaction system in the presence of a reducing agent, so that the development of the deuterated amino acid ester is greatly restricted, but a method for carrying out deuteration at a specific position by directly taking the amino acid ester as a raw material is not reported. Therefore, the development of an efficient, economical and universally applicable method for directly preparing the deuterated amino acid ester at a specific position becomes a hot spot which needs to be researched urgently.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a novel method for directly preparing deuterated amino acid ester compounds at specific positions by directly using amino acid esters as raw materials, wherein the method is rapid, efficient, cheap and high in universality.
According to the invention, one of the methods for preparing the deuterated amino acid ester by photocatalysis is characterized in that deuterated water and the amino acid ester compound shown as the formula I are used as reaction raw materials, a catalytic amount of Lewis acid, tetraphenylphosphonium chloride, tetraphenylboron salt, borane derivative and aluminum oxide are used as composite catalysts, and under the protection of nitrogen, the deuterated amino acid ester shown as the formula II is obtained by reaction at room temperature under ultraviolet light, wherein the reaction general formula is as follows:
in the formula, R 1 ，R 2 ，R 2 ' and R 3 Is any group.
OptionallyEarth, R 1 Is hydrogen, substituted or unsubstituted C 1-20 Alkyl, substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted C 3-20 Heteroaryl, substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 1-20 Alkoxycarbonyl, substituted or unsubstituted C 1-20 Acyl, substituted or unsubstituted C 6-20 aryl-C 1-20 Alkyl, substituted or unsubstituted C 6-20 An aroyl group.
R 2 Is hydrogen, substituted or unsubstituted C 1-20 Alkyl, substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted C 3-20 Heteroaryl, substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 6-20 aryl-C 1-20 An alkyl group.
R 2 ' Definitions and R 2 Is the same, and when R is 2 When it is hydrogen, R 2 ' is deuterium.
R 3 Is hydrogen, substituted or unsubstituted C 1-20 Alkyl, substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted C 3-20 Heteroaryl, substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 6-20 aryl-C 1-20 An alkyl group.
In any part of the present invention, the substituent in said "substituted or unsubstituted" is selected from halogen, C 1-6 Alkoxy radical, C 1-6 Alkyl, -CN, -NO 2 Halogen substituted C 1-6 Alkyl radical, C 1-6 One or more alkylthio groups. Preferably fluorine, chlorine, bromine, iodine, methoxy, ethoxy, propoxy, isopropoxy, tert-butoxy, methyl, ethyl, propyl, isopropyl, tert-butyl, isobutyl, -CN, -NO 2 One or more of trifluoromethyl, methylthio and ethylthio.
In any of the moieties of the invention, the heteroatom of heteroaryl, heterocycloalkyl is selected from N, O, S, P, se or Si.
In the present invention, said C 1-20 Alkyl radical, C 1-20 Acyl radical, C 1-20 Alkoxycarbonyl, C 6-20 Aryl radicals-C 1-20 The alkyl moiety in the alkyl group is linear or branched, and the carbon number of the alkyl group may be more preferably 1 to 6, and still more preferably 1 to 3. Examples of the alkyl group may include methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, isobutyl, n-pentyl, neopentyl, hexyl, 2-ethylhexyl, 2-butylhexyl, heptyl, octyl, nonyl, decyl, n-undecyl, n-dodecyl and the like.
In the present invention, said C 6-20 Aryl radical, C 6-20 Aroyl, C 6-20 aryl-C 1-20 The aryl group in the alkyl group is a monocyclic or polycyclic aryl group, and the number of carbon atoms for forming the aryl group may be further preferably 6 to 18, 6 to 14, or 6 to 12. Examples of the aryl group may include phenyl, naphthyl, anthryl, phenanthryl, fluorenyl, biphenyl, terphenyl, benzophenanthryl, pyrenyl, and the like,
A phenyl group, a fluoranthene group, and the like.
In the present invention, said C 3-20 The cycloalkyl group may be a monocyclic or polycyclic cycloalkyl group, and the number of carbon atoms for forming the cycloalkyl group may be further preferably 3 to 12, 3 to 8, or 3 to 6. Examples of cycloalkyl groups may include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl, bicyclo [3.2.1]Octane, spiro [5.5 ]]Undecane, and the like.
In the present invention, said C 3-20 The heteroaryl group may be a monocyclic or polycyclic heteroaryl group, and the number of carbons forming the heteroaryl group may be further preferably 2 to 18,2 to 12,2 to 8, or 2 to 6. Examples of heteroaryl groups may include thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, oxadiazolyl, triazolyl, pyridyl, bipyridyl, pyrimidinyl, triazinyl, acridinyl, pyridazinyl, pyrazinyl, quinolyl, quinazolinyl, quinoxalinyl, phenoxazinyl, phenothiazinyl, pyridopyrimidinyl, pyridopyrazinyl, isoquinolyl, indolyl, carbazolyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzofuranyl, benzothienyl, phenanthrolinyl, thiazolyl, isoxazolyl, thiadiazolyl, dibenzofuranyl, thieno, phenanthrolinyl, thiazolyl, isoxazolyl, thiadiazolyl, oxadiazolyl, and the likeThienyl, and the like.
Preferably, the amino acid ester compound of formula I has the following structure:
the second method for preparing deuterated amino acid esters by photocatalysis is characterized in that deuterated water and an amino acid ester compound shown as a formula I-1 are used as reaction raw materials, a catalytic amount of Lewis acid, tetraphenylphosphonium chloride, tetraphenylboron salt, borane derivatives and aluminum oxide are used as composite catalysts, and the deuterated amino acid esters shown as a formula II-1 are obtained by reacting at room temperature under ultraviolet light under the protection of nitrogen, wherein the general reaction formula is as follows:
the invention discloses a method for preparing deuterated amino acid esters by photocatalysis, which comprises the following specific steps:
(5) Dissolving a certain amount of amino acid ester compounds in deuterium water, adding a composite catalyst, and adding N 2 Fully and uniformly stirring under protection;
(6) The power is 5W-100W, the wavelength is under the irradiation of an ultraviolet lamp between 265nm and 400nm, and the full reaction is carried out for 0.5-24h at the temperature of 15-35 ℃;
(7) After the reaction is finished, the catalyst is removed by filtration, and the mixture is extracted by using a solvent with ethyl acetate/water =1 or butyl acetate/water volume ratio =1, and an organic phase is taken;
(8) And (4) separating by using column chromatography to obtain the deuterated amino acid ester compound.
The molar ratio of the amino acid ester compound to the deuterium oxide in the step (1) is 1.
The mol ratio of the amino acid ester compound to the composite catalyst in the step (1) is as follows in sequence: n (amino acid ester compound): n (Lewis acid): n (tetraphenylphosphonium chloride): n (tetraphenylboron salt): n (borane): n (alumina) =1:0.00005-0.5:0.00005-0.5:0.00005-0.5:0.00005-0.5:0.00005-0.5.
In the invention, the Lewis acid is FeCl 3 ，HCl，H 2 SO 4 ，CuCl 2 ，AgNO 3 And the like.
In the invention, the tetraphenylborate salt is one or more of sodium tetraphenylborate, potassium tetraphenylborate, lithium tetraphenylborate, rubidium tetraphenylborate and cesium tetraphenylborate.
In the invention, the borane derivative is B n H n 2- ，B n H n+1 - ，B n H n+2 ，C a B n-a H n-a+2 Wherein n is one of 6,7,8,9, 10, 12, 20 and 24; a is one of 1,2,3 and 4. If the borane needs cation coordination, the cation is one or more of metal cations, such as Li, na, K, ru, cs, mg, al and the like.
Compared with the prior art, the invention has the following advantages:
(1) The invention realizes the deuteration reaction of the amino acid ester compound by adopting the composite catalyst under the illumination for the first time;
(2) The invention adopts deuterium water as deuterium source, thus greatly reducing the deuterium cost;
(3) The invention adopts a photocatalysis method to obtain the deuterated amino acid ester compound, realizes the direct use of the amino acid ester compound as a raw material to perform deuteration on a specific site, does not need to prepare the imine acid ester and/or dehydroamino acid ester precursor, effectively saves the process steps, has the advantages of mild reaction, short reaction time, easy operation, good environment and the like, and is beneficial to the industrial production and application of the deuterated amino acid ester compound.
Drawings
FIG. 1 is a schematic representation of the methyl ester of D-BOC-D-alanine prepared in example 1 1 H NMR spectrum.
FIG. 2 is a schematic representation of the preparation of D-CBZ-glycine methyl ester from example 3 1 H NMR spectrum.
FIG. 3 is a schematic representation of the methyl ester of D-N-Boc-4-oxo-L-proline prepared in example 6 1 H NMR spectrum.
FIG. 4 is a drawing of the methyl ester of D-Cbz-L-alanine prepared in example 4 1 H NMR spectrum.
FIG. 5 is a drawing of the preparation of methyl D-N-Cbz-L-leucine ester from example 5 1 H NMR spectrum.
Detailed Description
The invention is explained in more detail below with reference to the figures and examples, without limiting the scope of the invention.
Example 1:
(1) Dissolving 500mmol of the amino acid ester compound in 25mol of deuterium water, adding composite catalyst (ferric chloride: 0.025mmol, tetraphenylphosphonium chloride: 0.025mmol, sodium tetraphenylborate: 0.5mmol, na) 2 B 12 H 12 :0.5mmol，Al 2 O 3 ：0.25mmol)，N 2 Fully and uniformly stirring under protection;
(2) Fully reacting for 8 hours at room temperature (25 ℃) under the irradiation of an ultraviolet lamp with the power of 5W and the wavelength of 365 nm;
(3) After the reaction, the catalyst was removed by filtration, extracted with ethyl acetate/water =1, and the organic phase was taken;
(4) Separating by column chromatography to obtain the deuterated amino acid ester compound shown in the formula. Isolated yield 91%, according to 1 The deuterium incorporation rate of this compound was 97% as calculated by H NMR spectrum.
Example 2:
(1) The above-mentioned10mmol of amino acid ester compounds are dissolved in 500mmol of deuterium water, and a composite catalyst (HCl: 0.1mmol, tetraphenylphosphonium chloride: 0.1mmol, tetraphenylboron potassium: 0.1mmol, cs) is added 2 B 10 H 10 :0.05mmol，Al 2 O 3 ：0.1mmol)，N 2 Fully and uniformly stirring under protection;
(2) Fully reacting for 4 hours at room temperature (25 ℃) under the irradiation of an ultraviolet lamp with the power of 25W and the wavelength of 265 nm;
(3) After the reaction, the catalyst was removed by filtration, extracted with butyl acetate/water =1, and the organic phase was taken;
(4) Separating by column chromatography to obtain the deuterated amino acid ester compound shown in the formula. Isolated yield 88%, according to 1 The deuterium incorporation efficiency of this compound was calculated to be 95% by H NMR spectroscopy.
Example 3:
(1) Dissolving 1mol of the amino acid ester compound in 100mol of deuterium water, and adding a composite catalyst (AgNO) 3 :0.05mmol, tetraphenylphosphonium chloride: 0.05mmol, sodium tetraphenylborate: 0.5mmol 2 B 3 H 7 :0.05mmol，Al 2 O 3 ：0.5mmol)，N 2 Fully and uniformly stirring under protection;
(2) Fully reacting for 24 hours at room temperature (30 ℃) under the irradiation of an ultraviolet lamp with the power of 50W and the wavelength of 395 nm;
(3) After the reaction, the catalyst was removed by filtration, extracted with butyl acetate/water =1, and the organic phase was taken;
(4) Separating by column chromatography to obtain the deuterated amino acid ester compound shown in the formula. Isolated yield 89%, according to 1 Calculation of the Compound by H NMR SpectroscopyThe doping rate of deuterium is 96%
Example 4:
(1) Dissolving 1mmol of the amino acid ester compound in 75mmol of deuterium water, and adding a composite catalyst (H) 2 SO 4 :0.25mmol, tetraphenylphosphonium chloride: 0.1mmol, sodium tetraphenylborate: 0.05mmol of 2 B 6 H 6 :0.05mmol mmol，Al 2 O 3 ：0.00005mmol)，N 2 Fully and uniformly stirring under protection;
(2) Fully reacting for 20 hours at room temperature (25 ℃) under the irradiation of an ultraviolet lamp with the power of 100W and the wavelength of 400 nm;
(3) After the reaction, the catalyst was removed by filtration, extracted with ethyl acetate/water =1, and the organic phase was taken;
(4) Separating by column chromatography to obtain the deuterated amino acid ester compound shown in the formula. Isolated yield 94% according to 1 The deuterium incorporation rate of this compound was 93% as calculated by H NMR spectrum
Example 5:
(1) Dissolving 0.25mmol of the amino acid ester compound in 20mmol deuterium water, and adding composite catalyst (CuCl) 2 :0.025mmol, tetraphenylphosphonium chloride: 0.125mmol, cesium tetraphenylboron: 0.125mmol,2,4-C 2 B 5 H 7 :0.125mmol，Al 2 O 3 ：0.025mmol)，N 2 Fully and uniformly stirring under protection;
(2) Fully reacting for 8.5 hours at room temperature (15 ℃) under the irradiation of an ultraviolet lamp with the power of 50W and the wavelength of 370 nm;
(3) After the reaction, the catalyst was removed by filtration, extracted with ethyl acetate/water =1, and the organic phase was taken;
(4) Separating by column chromatography to obtain the deuterated amino acid ester compound shown in the formula. Isolated yield 85%, according to 1 The deuterium incorporation rate of this compound was 96% as calculated by H NMR spectrum
Example 6:
(1) Dissolving 1.5mmol of the amino acid ester compound in 150mmol of deuterium water, adding composite catalyst (0.3 mmol of ferric nitrate, 0.375mmol of tetraphenylphosphonium chloride, 0.15mmol of rubidium tetraphenylborate, na) 2 B 6 H 7 :0.075mmol，Al 2 O 3 ：0.75mmol)，N 2 Fully and uniformly stirring under protection;
(2) Fully reacting for 24 hours at room temperature (25 ℃) under the irradiation of an ultraviolet lamp with the power of 10W and the wavelength of 365 nm;
(3) After the reaction, the catalyst was removed by filtration, extracted with butyl acetate/water =1, and the organic phase was taken;
(4) Separating by column chromatography to obtain the deuterated amino acid ester compound shown in the formula. The isolated yield was 90%, based on 1 Calculation of deuterium incorporation of the Compound by H NMR SpectroscopyThe ratio is 95 percent
Example 7:
(1) Dissolving 50mmol of the amino acid ester compound in 750mmol of deuterium water, and adding composite catalyst (ferric chloride: 0.05mmol, tetraphenylphosphorous chloride: 0.5mmol, lithium tetraphenylboron: 5mmol,1, 12-C) 2 B 10 H 12 :2.5mmol，Al 2 O 3 ：0.5mmol)，N 2 Fully and uniformly stirring under protection;
(2) Fully reacting for 6 hours at room temperature (15 ℃) under the irradiation of an ultraviolet lamp with the power of 65W and the wavelength of 300 nm;
(3) After the reaction, the catalyst was removed by filtration, extracted with ethyl acetate/water =1, and the organic phase was taken;
(4) Separating by column chromatography to obtain the deuterated amino acid ester compound shown in the formula. Isolated in 93% yield according to 1 The deuterium incorporation rate of this compound was 98% as calculated by H NMR spectrum
Example 8:
(1) 0.1mmol of the amino acid ester compound is dissolved in 8mmol deuterium water, and a composite catalyst (ferric chloride: 0.01mmol, HCl：0.03mmol，Na 2 B 12 H 12 :0.015mmol，RuB 10 H 11 :0.015mmol,Al 2 O 3 ：0.03mmol)，N 2 Fully and uniformly stirring under protection;
(2) Fully reacting for 0.5h at room temperature (25 ℃) under the irradiation of an ultraviolet lamp with the power of 100W and the wavelength of 365 nm;
(3) After the reaction, the catalyst was removed by filtration, extracted with butyl acetate/water =1, and the organic phase was taken;
(4) Separating by column chromatography to obtain the deuterated amino acid ester compound shown in the formula. Isolated in 90% yield 1 The deuterium incorporation rate of this compound was 98% as calculated by H NMR spectrum
Example 9:
(1) Dissolving 100mmol of the above amino acid ester compounds in 6mol deuterium water, and adding composite catalyst (Cu (NO) 3 ) 2 ：1mmol，Fe(NO 3 ) 3 ：1mmol,AgNO 3 :1mmol, tetraphenylphosphonium chloride: 10mmol, potassium tetraphenylborate: 5mmol of Na 2 B 12 H 12 :0.05mmol，NaCB 9 H 10 :0.05mmol，Na 2 B 24 H 24 :0.05mmol，Al 2 O 3 ：0.1mmol)，N 2 Fully and uniformly stirring under protection;
(2) Fully reacting for 24 hours at room temperature (25 ℃) under the irradiation of an ultraviolet lamp with the power of 100W and the wavelength of 395 nm;
(3) After the reaction, the catalyst was removed by filtration, extracted with butyl acetate/water =1, and the organic phase was taken;
(4) Separating by column chromatography to obtainDeuterated amino acid ester compounds of the formula. Isolated yield 94% according to 1 The deuterium incorporation rate of the compound was 99% as calculated by H NMR spectrum
Example 10:
(1) Dissolving 25mmol of the amino acid ester compound in 2.25mol of deuterium water, adding a composite catalyst (HCl: 1.25mmol, tetraphenylphosphonium chloride: 0.0625mmol, cesium tetraphenylborate: 6.25mmol, B) 10 H 12 :0.0625mmol，Al 2 O 3 ：1.25mmol)，N 2 Fully and uniformly stirring under protection;
(2) Fully reacting for 8 hours at room temperature (25 ℃) under the irradiation of an ultraviolet lamp with the power of 45W and the wavelength of 360 nm;
(3) After the reaction, the catalyst was removed by filtration, extracted with ethyl acetate/water =1, and the organic phase was taken;
(4) Separating by column chromatography to obtain the deuterated amino acid ester compound shown in the formula. Isolated in 93% yield according to 1 The deuterium incorporation rate of this compound was 96% as calculated by H NMR spectrum
The foregoing lists merely illustrate specific embodiments of the invention. It is obvious that the invention is not limited to the above embodiments, but that many variations are possible. All changes which can be directly derived or suggested by a person skilled in the art of deuterated drugs from the disclosure of the present invention, such as lewis acids in composite catalysts, tetraphenylborate salts, boranes, which can be single or two or more, for example, examples 8,9, etc., and amino acid ester compounds which can be other than the above examples, amino acid ester compounds with any other groups, etc., are considered to be within the scope of the present invention.
Claims (5)
1. A method for preparing deuterated amino acid esters by photocatalysis is characterized in that deuterated water and amino acid ester compounds of formula I are used as reaction raw materials, catalytic amount of Lewis acid, tetraphenylphosphonium chloride, tetraphenylboron salt, borane derivatives and aluminum oxide are used as composite catalysts, and the deuterated amino acid esters of formula II are obtained by room-temperature reaction under ultraviolet light under the protection of nitrogen, wherein the general reaction formula is as follows:
in the formula, R 1 Is substituted or unsubstituted C 1-20 Alkyl, substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 1-20 Alkoxycarbonyl, substituted or unsubstituted C 6-20 aryl-C 1-20 An alkyl group;
R 2 is hydrogen, substituted or unsubstituted C 1-20 Alkyl, substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted C 3-20 Heteroaryl, substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 6-20 aryl-C 1-20 An alkyl group;
R 2 ' Definitions and R 2 Is the same, and when R is 2 When it is hydrogen, R 2 ' is deuterium;
R 3 is substituted or unsubstituted C 1-20 Alkyl, substituted or unsubstituted C 6-20 Aryl, substituted or unsubstituted C 3-20 Cycloalkyl, substituted or unsubstituted C 6-20 aryl-C 1-20 An alkyl group;
wherein the substituent in the "substituted or unsubstituted" is selected from halogen, C 1-6 Alkoxy radical, C 1-6 Alkyl, -CN, -NO 2 Halogen substituted C 1-6 Alkyl radical, C 1-6 One or more alkylthio groups;
wherein the Lewis acid is FeCl 3 ，HCl，H 2 SO 4 ，CuCl 2 ，AgNO 3 One or more of the above;
the tetraphenylborate salt is one or more of sodium tetraphenylborate, potassium tetraphenylborate, lithium tetraphenylborate, rubidium tetraphenylborate and cesium tetraphenylborate;
the borane derivative is B n H n 2- ，B n H n+1 - ，B n H n+2 ，C a B n-a H n-a+2 Wherein n is one of 6,7,8,9, 10, 12, 20 and 24; a is one of 1,2,3 and 4; if the borane derivative needs cation coordination, the cation is one or more of Li, na, K, ru, cs, mg or Al.
2. The method of claim 1, wherein the amino acid ester compound of formula I has the following structure:
3. the method according to claim 1, characterized by the following specific steps:
(1) Dissolving a certain amount of amino acid ester compounds in deuterium water, adding a composite catalyst, N 2 Fully and uniformly stirring under protection;
(2) The power is 5W-100W, the wavelength is under the irradiation of an ultraviolet lamp between 265nm and 400nm, and the reaction is fully carried out for 0.5-24h at the temperature of 15-35 ℃;
(3) After the reaction is finished, the catalyst is removed by filtration, and the mixture is extracted by using a solvent with ethyl acetate/water =1 or butyl acetate/water volume ratio =1, and an organic phase is taken;
(4) And separating by column chromatography to obtain the deuterated amino acid ester compound.
4. The preparation method according to claim 3, wherein the molar ratio between the amino acid ester compound and the deuterium oxide is 1.
5. The preparation method according to claim 4, wherein the molar ratio between the amino acid ester compound and the composite catalyst is, in order: n (amino acid ester compound): n (Lewis acid): n (tetraphenylphosphonium chloride): n (tetraphenylboron salt): n (borane derivative): n (alumina) =1:0.00005-0.5:0.00005-0.5:0.00005-0.5:0.00005-0.5:0.00005-0.5.
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