Synthesis method of chiral m-aminomethylene phenylalanine derivative

Abstract

The invention provides a method for synthesizing a chiral m-aminomethylene phenylalanine derivative by reaction in a low-cost catalytic scheme. The synthesis method has the advantages of simple flow, convenient post-treatment, cheap and easily available starting materials, and easy industrial production. And # imgabs0 #.

Description

Technical Field

[0001] The present application relates to the field of pharmaceutical intermediate synthesis, and in particular, to a method for synthesizing chiral non-natural amino acid derivatives. Background Art

[0002] Chiral m-aminomethylenephenylalanine has a great application value in the field of drug synthesis. For example, Novartis's drug CU2010, Merck's drug MK0616, and UCB's following molecules in the biological testing and preclinical stages all contain this amino acid fragment. .

[0003] Although the related intermediate molecules have begun to show their application value, there are few reports on the synthesis of related compounds and derivatives. The main synthetic idea is to reduce the phenylalanine of the meta-cyano group. Bioorganic and Medicinal Chemistry , 2011, vol. 19, # 23, p. 7236 – 7243 reported the following synthetic route: , This synthetic route uses L-m-cyanophenylalanine as the starting material and undergoes 7 steps of reaction to obtain the target orthogonally protected m-aminomethylenephenylalanine derivative with an overall yield of 18.3%.

[0004] There are not many literature reports on the synthesis of L-m-cyanophenylalanine. In patent CN1795183B applied by the German company Verix in 2004, the following enzymatic splitting route was reported in Example 1 (

[0073] to

[0079] ): , This synthetic route uses m-cyanobenzyl bromide as the starting material and undergoes multiple steps of reaction to obtain the target L-m-cyanophenylalanine with a total yield of 24.1%. The atom economy of enzymatic hydrolysis is not high, resulting in a large amount of isomer molecules being wasted.

[0005] literature Journal of Medicinal Chemistry, 2018, vol. 61, # 16, p. 7358 –7373 reported a coupling method using L-serine as the starting material to prepare L-m-cyanophenylalanine, but the yield of the coupling step was only 28%. .

[0006] Therefore, exploring a low-cost, high-efficiency, and industrially convenient method for synthesizing related compounds has practical scientific significance and economic value. Summary of the invention

[0007] The purpose of the present application is to provide a method for preparing the compound of formula VII.

[0008] , (1) a diacylimide compound of the compound of formula I undergoes a substitution reaction to obtain a compound of formula II; (2) the compound of formula II undergoes a Horner-Wordsworth-Emmons reaction with a phosphate compound to obtain a compound of formula III; (3) the compound of formula III is subjected to a chiral transition metal catalytic hydrogenation reaction to obtain the compound of formula IV; (4) removing the protecting group from the compound of formula IV under acidic conditions to obtain the compound of formula V; (5) The compound of formula V is complexed with copper ions and the tert-butyloxycarbonyl group is selectively protected to obtain the compound of formula VI; (6) protecting the compound of formula VI with a second protecting group under alkaline conditions to obtain a compound of formula VII; Wherein, the fragments of R1 and R1' groups may be the following structures: , The R2 group is a C1~C7 hydrocarbon, The R3 group is tert-butyloxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, acetyl, benzoyl.

[0009] If the hydrazinolysis conditions are changed, the phthaloyl group can also serve as the nitrogen protecting group for the R1 and R1' groups. .

[0010] Compared with the prior art, the method for synthesizing the meta-aminomethylenephenylalanine derivative compound VII of the present application has the following advantages: (1) The catalytic hydrogenation technology has high diastereoselectivity, reduces the loss of isomers, and improves atom economy; (2) Selecting protecting groups with similar removal conditions, all protecting groups can be removed in one step under acidic conditions, which has high production efficiency; (3) The use of copper ion complexation can selectively protect the target amino group, avoid the orthogonal use of different protecting groups, shorten the reaction steps, and improve efficiency. DETAILED DESCRIPTION

[0011] The following examples are used to describe the implementation methods of the present application. Those skilled in the art should recognize that these specific examples only illustrate the implementation technical solutions selected to achieve the purpose of the present application, and are not limitations on the technical solutions. According to the teachings of the present application, it is obvious to improve the technical solutions of the present application in combination with the prior art, and all of them belong to the scope of protection of the present application.

[0012] The implementation conditions used in the examples can be further adjusted according to specific requirements, and the implementation conditions not specified are usually the conditions in routine experiments.

[0013] Example 1A , Compound 1 (1.0 eq, 1.2 g), succinimide (2.0 eq), potassium carbonate (2.0 eq), and acetone (25 vol) were added to the reaction flask for reflux reaction (50°C) for 2-3 h. After the reaction was completely cooled to room temperature, 25 vol of water was added to quench the reaction, and then the mixture was concentrated at 40°C until no droplets were left. 20 vol of DCM was added for extraction, and the aqueous phase was extracted once with 10 vol of DCM. The organic phases were combined and concentrated to dryness at 40°C to obtain 1.8 g of light yellow liquid compound 2 with a purity of 97.55%. Add 1.0eq of compound 2 described in the previous paragraph, phosphate reactant (2.0eq), and DCM (25vol) to the reaction flask, control the temperature to 0~10℃, and start stirring; add 2.0eq of tetramethylguanidine dropwise, and after the dropwise addition, move the reaction to room temperature for reaction; after the reaction is complete, add 25vol of water to quench the reaction, stir and separate the liquids, and continue to extract the aqueous phase with 10vol of DCM once; concentrate the DCM phase to dryness at 40℃ to obtain a waxy solid; add 20vol of EA to pulp; cool to 0~10℃ and stir for 0.5 h, filter; obtain a white solid, and dry it at 50℃; weigh 1.72 g, with a yield of 86% and a purity of 98.50%; Mass spectral data of compound 3a: [M+H] + =331.21.

[0014] Example 1B , Compound 1 (1.0 eq, 0.43 g), succinimide (2.0 eq), potassium carbonate (2.0 eq), and acetone (25 vol) were added to the reaction flask for reflux reaction (50°C) for 2-3 h. After the reaction was completely cooled to room temperature, 25 vol of water was added to quench the reaction, and then the mixture was concentrated at 40°C until no droplets were left. 20 vol of DCM was added for extraction, and the aqueous phase was extracted once with 10 vol of DCM. The organic phases were combined and concentrated to dryness at 40°C to obtain compound 2 with a purity of 96.35%. Add 1.0eq of compound 2 described in the above paragraph, phosphate reactant (2.0eq), and DCM (25vol) to the reaction flask, control the temperature to 0~10℃, and start stirring; add 2.0eq of tetramethylguanidine dropwise, and after the dropwise addition, move the reaction to room temperature for reaction; after the reaction is complete, add 25vol of water to quench the reaction, stir and separate the liquids, and continue to extract the aqueous phase with 10vol of DCM once; concentrate the DCM phase to dryness at 40℃ to obtain an off-white solid; add 10vol of DCM to pulp; cool to 0~10℃ and stir for 0.5h, filter; obtain a white solid, and dry it at 50℃; weigh 0.62g, with a yield of 90% and a purity of 99.02%; Mass spectral data of compound 3b: [M+H] + =345.14; NMR data of compound 3b: 1 H NMR (400 MHz, CDCl3) d 7.65 (s, 1H), 7.29-7.44(m, 4H), 7.21 (s, 1H), 4.63 (s, 1H), 4.30 (t, 2H, J=7.16), 2.72 (s, 4H), 2.19(s, 3H), 1.36 (t, 3H, J=7.20).

[0015] Example 2 , Compound 1 (1.0 eq, 2.0 g), sodium diformamide (2.0 eq), potassium carbonate (2.0 eq), and acetone (25 vol) were added to the reaction flask for reflux reaction (50°C) for 2-3 h. After the reaction was completely cooled to room temperature, 25 vol of water was added to quench the reaction, and then the mixture was concentrated at 40°C until no droplets were left. 20 vol of DCM was added for extraction, and the aqueous phase was extracted once with 10 vol of DCM. The organic phases were combined and concentrated to dryness at 40°C to obtain 1.5 g of light yellow liquid compound 4 with a purity of 91.73%. Add 1.0eq of compound 4 described in the above paragraph, phosphate reactant (2.0eq), DCM (25vol) to the reaction flask, control the temperature to 0~10℃, and start stirring; add 2.0eq of tetramethylguanidine dropwise, and after the dropwise addition, move the reaction to room temperature for reaction; after the reaction is complete, add 25vol of water to quench the reaction, stir and separate the liquids, and continue to extract the aqueous phase with 10vol of DCM once; concentrate the DCM phase to dryness at 40℃ to obtain a waxy solid; add 20vol of EA to pulp; cool to 0~10°C and stir for 0.5 h, filter; obtain a white solid, and dry it at 50℃; weigh 0.83 g, with a yield of 30% and a purity of 99.15%; Mass spectrometry data of compound 5: [M+Na] + =299.08; NMR data of compound 5: 1 H NMR (400 MHz, d-DMSO) d 9.63 (s, 1H), 8.53 (brs,1H), 7.45-7.55 (m, 2H), 7.39 (t, 1H, J=7.68Hz), 7.29 (d, 1H, J=7.84Hz), 7.16(s, 1H), 4.33 (d, 1H, J=6.08Hz), 3.71 (s, 3H), 2.01 (s, 3H).

[0016] Example 3 , Compound 5 (1.0 eq, 100 mg), Rh[(NBD)(Rc,Sp-DuanPhos)]BF4 (6 mg, 6% w / w), and methanol (1 mL) were added to the reaction flask, and hydrogen was added to the pressure of 4.0 MPa. The reaction was carried out at 50°C for 15 h. After the reaction was complete, the temperature was lowered to room temperature and concentrated to dryness at 40°C to obtain 0.1 g of light yellow liquid compound 6 with a purity of 99.91% and an ee of 99.76%. Mass spectrometry data of compound 6: [M+Na] + =301.11; NMR data of compound 6: 1 H NMR (400 MHz, CDCl3) d 8.15 (s, 1H), 6.69-7.24(m, 5H), 6.68 (d, 1H, J=7.92), 4.79 (ddd, 1H, J1=5.48, J2=7.28, J3=12.96), 4.37 (d, 2H, J=5.96), 3.69 (s, 3H), 3.09 (dd, 1H, J1=5.48, J2=13.84), 2.97 (dd, 1H, J1=7.00, J2=13.80), 1.91 (s, 3H).

[0017] Example 4 , Compound 3 (1.0 eq, 100 mg), Rh[(NBD)(Sc,Rp-DuanPhos)]BF4 (7 mg, 7% w / w), and methanol (1 mL) were added to the reaction flask, and hydrogen was added to the pressure of 4.0 MPa. The reaction was carried out at 50 °C for 15 h. After the reaction was complete, the temperature was lowered to room temperature and concentrated to dryness at 40 °C to obtain 0.1 g of light yellow liquid compound 7 with a purity of 97.75% and an ee of 97.42%. Mass spectral data of compound 7: [M+H] + =333.15; NMR data of compound 7: 1 H NMR (400 MHz, CDCl3) d 7.20-7.33 (m, 2H), 7.12(s, 1H), 7.01 (d, 1H, J=7.24), 5.97 (d, 1H, J=8.00), 4.85 – 4.95 (m, 1H),4.66 (d, 1H, J=14.0 ), 4.59 (d, 1H, J=14.0), 3.77 (s, 3H), 3.03-3.20 (m, 2H), 2.73 (s, 4H), 2.02 (s, 3H).

[0018] Example 5 , Add 0.7 g of crude compound 7 to the reaction flask, then add 3.5 mL of concentrated hydrochloric acid and 3.5 mL of water, and place at an external temperature of 105°C to start the reaction. Reflux for 48 hours until the reaction is complete, spin dry the solvent to obtain a crude product that is directly used in the next step; Mass spectral data of compound 8: [M-2HCl+H] + =195.16; NMR data of compound 8: 1 H NMR (400 MHz, d-DMSO) d 8.59 (brs, 6H), 7.40 –7.46 (m, 2H), 7.37 (t, 1H, J=7.48), 7.27 (d, 1H, J=7.52), 4.15 (t, 1H, J=6.48), 3.97 (d, 1H, J=5.16), 3.17 (dd, 2H, J1=3.32, J2=6.28).

[0019] Example 6 , The crude product of Compound 8 of Example 5 was added to the reaction flask, and 0.3 g of copper sulfate pentahydrate was added and stirred at room temperature for 3 h. A solution of 700 mg of Boc2O in 8 mL of acetone was added and the reaction was completed in 4 hours. The mixture was filtered and the filter cake was washed with 3 mL of water. The filter cake was drained to obtain 1.1 g of the product as a light blue solid with a purity of 81.04%. Mass spectral data of compound 9: [M+H] + =295.18.

[0020] Example 7 , Add 0.5 g of crude compound 6 to the reaction flask, then add 2 mL of concentrated hydrochloric acid and 1 mL of water, and place at an external temperature of 100°C to start the reaction. Reflux for 2 h to complete the reaction, spin dry the solvent to obtain a crude product that is directly used in the next step; Mass spectral data of compound 8: [M-2HCl+H] + =195.16; NMR data of compound 8: 1 H NMR (400 MHz, d-DMSO) d 8.59 (brs, 6H), 7.40 –7.46 (m, 2H), 7.37 (t, 1H, J=7.48), 7.27 (d, 1H, J=7.52), 4.15 (t, 1H, J=6.48), 3.97 (d, 1H, J=5.16), 3.17 (dd, 2H, J1=3.32, J2=6.28).

[0021] Example 8 , Add 100 mg of the light blue copper salt solid of compound 9 in Example 6 to the reaction bottle, add 1 mL of water, then add 60 mg of EDTA-Na and 80 mg of sodium bicarbonate, stir to dissolve; then add 0.5 mL of THF to dissolve completely; add 100 mg of FmocOSu to react; monitor the reaction for 1 hour; quench the reaction with 3 mL of saturated ammonium chloride, extract three times with 6 mL of EA, combine the organic phases and spin dry, use silica gel column chromatography, use DCM: MeOH 20:1 as the eluent, UV254 color development, spin dry, and drain to obtain 70 mg of the product with a purity of 91.57%. Using compound 3 as the separation substrate to compound 10, the total yield of the four-step reaction is about 70%, and the ee is 95.96%; Mass spectral data of compound 10: [MH] - =515.38; NMR data of compound 10: 1 H NMR (400 MHz, d-DMSO) d12.79 (brs, 1H), 7.88(d, 2H, J=7.52), 7.75 (d, 1H, J=8.4), 7.67 (t, 2H, J=7.64), 7.05 – 7.45 (m,9H), 4.05 – 4.25 (m, 6H), 3.07 (dd, 1H, J1=4.16, J2=13.68), 2.88 (dd, 1H, J1=10.52, J2=13.48), 1.40 (s, 9H).

[0022] Example 9 , Compound 1 (1.0 eq, 30.0 g), sodium diformamide (2.0 eq), potassium carbonate (2.0 eq), and acetone (25 vol) were added to the reaction flask for reflux reaction (50°C) for 2-3 h. After the reaction was completely cooled to room temperature, 25 vol of water was added to quench the reaction, and then the mixture was concentrated at 40°C until no droplets were left. 20 vol of DCM was added for extraction, and the aqueous phase was extracted once with 10 vol of DCM. The organic phases were combined and concentrated at 40°C to dryness to obtain 20 g of light yellow liquid compound 4. Add 1.0eq of compound 4 described in the previous paragraph, phosphate reactant (2.0eq), and DCM (25vol) to the reaction flask, control the temperature to 0-10℃, and start stirring; add 2.0eq of tetramethylguanidine dropwise, and move the reaction to room temperature after the addition is complete; after the reaction is complete, add 25vol of water to quench the reaction, stir and separate the liquids, and continue to extract the aqueous phase with 10vol of DCM once; concentrate the DCM phase at 40℃ to 20vol, and the product precipitates to obtain a white solid; control the temperature to 10-20℃ and stir for 2h, filter and drain, and dry at 50℃; weigh 23.7 g, with a yield of 57% and a purity of >99.9%; Mass spectrometry data of compound 5: [M+Na] + =299.08; NMR data of compound 5: 1 H NMR (400 MHz, d-DMSO) d 9.63 (s, 1H), 8.53 (brs,1H), 7.45-7.55 (m, 2H), 7.39 (t, 1H, J=7.68Hz), 7.29 (d, 1H, J=7.84Hz), 7.16(s, 1H), 4.33 (d, 1H, J=6.08Hz), 3.71 (s, 3H), 2.01 (s, 3H).

[0023] Example 10 , Compound 5 (1.0 eq, 20 g), Rh[(NBD)(Sc,Rp-DuanPhos)]BF4 (20 mg, 0.1% w / w), and methanol (140 mL) were added to the reaction flask, and hydrogen was added to the pressure of 4.0 MPa. The reaction was carried out at 50 °C for 15 h. After the reaction was completely cooled to room temperature, the reaction was concentrated to dryness at 40 °C to obtain 20 g of light yellow liquid compound 6 with a purity of 99.32% and an ee of 97.84%. Mass spectrometry data of compound 6: [M+Na] + =301.11; NMR data of compound 6: 1 H NMR (400 MHz, CDCl3) d 8.15 (s, 1H), 6.69-7.24(m, 5H), 6.68 (d, 1H, J=7.92), 4.79 (ddd, 1H, J1=5.48, J2=7.28, J3=12.96), 4.37 (d, 2H, J=5.96), 3.69 (s, 3H), 3.09 (dd, 1H, J1=5.48, J2=13.84), 2.97 (dd, 1H, J1=7.00, J2=13.80), 1.91 (s, 3H).

[0024] Embodiment 11 , 20 g of the crude compound 6 obtained in Example 10 was added to the reaction bottle, and then 40 mL of concentrated hydrochloric acid and 40 mL of water were added, and the reaction was started at an external temperature of 100° C. Reflux for 2 h to complete the reaction, and the solvent was spin-dried to obtain 18.5 g of a crude product of a yellow viscous compound, which was directly used in the next step reaction; Mass spectral data of compound 8: [M-2HCl+H] + =195.16; NMR data of compound 8: 1 H NMR (400 MHz, d-DMSO) d 8.59 (brs, 6H), 7.40 –7.46 (m, 2H), 7.37 (t, 1H, J=7.48), 7.27 (d, 1H, J=7.52), 4.15 (t, 1H, J=6.48), 3.97 (d, 1H, J=5.16), 3.17 (dd, 2H, J1=3.32, J2=6.28).

[0025] Example 12 , 9.0 g of the crude product of compound 8 of Example 11 and 50 mL of water were added to the reaction flask, and the pH was adjusted to 6-7 with NaOH, and then 4.6 g of copper sulfate pentahydrate and 6 g of sodium bicarbonate were added, and the mixture was stirred at room temperature for 3 h. A solution of 11.62 g of Boc2O in 55 mL of acetone was added, and the reaction was stirred for 5 h; the mixture was filtered, and the filter cake was drained to obtain a light blue copper salt solid of about 20 g, which was directly used in the next reaction; Mass spectral data of compound 9: [M+H] + =295.18.

[0026] Embodiment 13 , 20 g of the light blue copper salt solid of compound 9 of Example 12 was added to a reaction bottle, added to 150 mL of water, and then 6.0 g of EDTA-Na and 7.13 g of sodium bicarbonate were added, and stirred to dissolve; 60 mL of THF was added to dissolve it completely; 6.9 g of FmocOSu was added to react; the reaction was monitored for 1 h to be complete; 50 mL of saturated ammonium chloride was used to quench the reaction, 100 mL of ethyl acetate was used to extract the reaction solution and the aqueous phase, the organic phases were combined and spin-dried to obtain a white solid, which was recrystallized from 150 mL of ethyl acetate to obtain 7.8 g of the product, and the total yield of the four-step reaction was about 42%, the purity was 98.49%, and the ee was 98.08%; Mass spectral data of compound 10: [MH] - =515.38; NMR data of compound 10: 1 H NMR (400 MHz, d-DMSO) d 7.88 (d, 2H, J=7.56),7.65 - 7.75 (m, 2H), 7.05 - 7.45 (m, 9H), 4.05 - 4.25 (m, 6H), 3.09 (dd, 1H,J1=4.28, J2=13.84), 2.88 (dd, 1H, J1=9.12, J2=13.68), 1.38 (s, 9H).

[0027] Embodiment 14 , Compound 1 (1.0 eq, 0.2 g), bis-Boc amine (2.0 eq), sodium hydroxide (2.0 eq), and THF (2 ml) were added to the reaction flask and reacted at room temperature (25°C) for 2-3 h. After the reaction was completely cooled to room temperature, 25 vol of water was added to quench the reaction, and then the mixture was concentrated at 40°C until no droplets were left. 20 vol of DCM was added for extraction, and the aqueous phase was extracted once with 10 vol of DCM, and concentrated to dryness at 40°C. Column chromatography was performed using n-heptane / ethyl acetate = 15 / 1-4 / 1 to obtain 0.48 g of the product. Add 1.0eq of compound 11, 0.3g of phosphate reactant (0.32g), and DCM (10ml) to the reaction flask, control the temperature at 0~10℃, and start stirring; add 2.0eq of tetramethylguanidine dropwise, and move the reaction to room temperature after the dropwise addition; after the reaction is complete, add 8mL of water to quench the reaction, stir and separate the liquids, and continue to extract the aqueous phase with 10vol of DCM once; concentrate the DCM phase at 40℃ to dryness to obtain a white solid; use n-heptane / ethyl acetate = 15 / 1~1 / 1 column chromatography to obtain 0.15g of the product. The yield is 33%, and the purity is 97.53%; Mass spectral data of compound 12: [M+Na] + =471.28; NMR data of compound 12: 1 H NMR (400 MHz, CDCl3) d 7.45(s, 1H), 7.20 – 7.40(m, 3H), 7.15 (s, 1H), 4.76 (s, 2H), 3.84 (s, 3H), 2.16 (s, 3H), 1.45 (s,18H).

[0028] Embodiment 15 , Add 200 mg (30% content) of the light blue copper salt solid of compound 9 in reference example 6 to the reaction bottle, add 3 mL of water, then add 120 mg of EDTA-Na and 142 mg of sodium bicarbonate, stir to dissolve; then add 1.2 mL of THF to dissolve completely; add 70 mg of benzyl chloroformate to react; monitor the reaction for 1 h; quench the reaction with 5 mL of saturated ammonium chloride, extract with 20 mL of EA, wash once with 5 mL of saturated brine, use silica gel column chromatography, use ethyl acetate: n-heptane = 1:1 as the eluent, spin dry, and drain to obtain 176 mg of the product with a purity of 89.12% and a yield of 72%; Mass spectral data of compound 13: [MH] - =427.37; NMR data of compound 13: 1H NMR (400 MHz, d-DMSO) d 7.63 (d, 2H, J=8.28),7.20 - 7.40 (m, 7H), 7.05 - 7.19 (m, 3H), 5.01 (d, 1H, J=12.64), 4.96 (d, 1H,J=12.72), 4.05 - 4.22 (m, 3H), 3.05 (dd, 1H, J1=3.92, J2=13.60), 2.82 (dd,1H, J1=10.56, J2=13.60), 1.40 (s, 9H).

[0029] The present application includes but is not limited to the above embodiments. Any equivalent substitution or partial improvement made under the spirit and principle of the present application shall be deemed to be within the protection scope of the present application.

Claims

1. A method for preparing a compound of formula V, comprising the following steps: (1) a diacylimide compound of the compound of formula I undergoes a substitution reaction to obtain a compound of formula II; (2) the compound of formula II undergoes a Horner-Wordsworth-Emmons reaction with a phosphate compound to obtain a compound of formula III; (3) the compound of formula III is subjected to a chiral transition metal catalytic hydrogenation reaction to obtain the compound of formula IV; (4) removing the protecting group from the compound of formula IV under acidic conditions to obtain the compound of formula V; ， in, R1 and R1' are H or can remove leaving groups under acidic conditions, R2 is a C1-C7 hydrocarbon, and the absolute configurations of compound IV and compound V are (R) configuration, (S) configuration or a mixture thereof.

2. The synthesis method according to claim 1, wherein the R1 and R1' groups are H, formyl, tert-butyloxycarbonyl, or the R1 and R1' groups together form a succinyl group as follows: 。 3. The method according to claim 1, wherein the R2 group is a methyl group or an ethyl group.

4. The chiral transition metal catalyzed hydrogenation reaction as claimed in claim 1 obtains a compound of formula IV, wherein the diastereomeric excess is above 90%.

5. A compound having a structure of formula III: ， in, R1 and R1' are H or nitrogen atom protecting groups, the olefin is E-form, Z-form, or a mixture of E / Z structures, and R2 is a C1-C7 hydrocarbon.

6. The compound as claimed in claim 5, wherein R1 and R1' groups are H, formyl, tert-butyloxycarbonyl, or R1 and R1' groups together form succinyl, phthaloyl as follows: 。 7. The compound as claimed in claim 5, wherein the R2 group is methyl or ethyl.

8. A method for preparing a compound of formula VII, (1) The compound of formula V is complexed with copper ions and the tert-butyloxycarbonyl group is selectively protected to obtain the compound of formula VI; (2) protecting the α-nitrogen of amino acid of the compound of formula VI under alkaline conditions to obtain the compound of formula VII; ， in, The absolute configurations of compound V, compound VI and compound VII are (R) configuration, (S) configuration or a mixture thereof, and R3 is a nitrogen atom protecting group.

9. The method according to claim 8, wherein R3 is tert-butyloxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, acetyl or benzoyl.

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