Optically active amino acid salts and methods of making same

Abstract

The invention discloses an optically active glufosinate-lysine salt with a structure as shown in a formula (I-IV) as shown in the specification. The invention also discloses a method for preparing the optically active glufosinate-lysine salt, which comprises the following steps: taking D, L-glufosinate or a salt thereof as a raw material, taking D-lysine or L-lysine as a resolving agent, and taking D-lysine or L-lysine as a resolving agent to obtain the optically active glufosinate-lysine salt. And obtaining the L-glufosinate-D-lysine salt, the D-glufosinate-D-lysine salt, the L-glufosinate-L-lysine salt or the D-glufosinate-L-lysine salt through a resolution reaction, crystallization and filtration in a suitable resolving agent system. The D-glufosinate-D-lysine salt or the L-glufosinate-L-lysine salt is prepared by taking the D-glufosinate-D-lysine salt as a resolution solvent of an anhydrous system; and the L-glufosinate-D-lysine salt or the D-glufosinate-L-lysine salt is prepared by using a resolution solvent as an aqueous system.

Description

Technical Field

[0001] The present disclosure relates to optically active glufosinate salts, including L-glufosinate-D-lysine salt, D-glufosinate-D-lysine salt, L-glufosinate-L-lysine salt, and D-glufosinate-L-lysine salt. The present disclosure also relates to methods for preparing these salts from D,L-glufosinate and optically active lysine, and the use of these salts in agriculture to control undesirable vegetation, including in the propagation of transgenic crop plants. Background Art

[0002] Glufosinate, also known as 2-amino-4-(hydroxymethylphosphinyl)butyric acid ammonium salt, was first developed by Hoechst in 1987 and successfully commercialized under the trade name BASTA.

[0003] Glufosinate is an organophosphorus herbicide and one of the world's three major non-selective herbicides. The expansion of the global paraquat ban, the continued presence of glyphosate resistance, and the promotion of genetic engineering have effectively driven the rapid growth of glufosinate demand. In recent years, glufosinate-resistant genetically modified crops have been promoted and planted in selected countries in Asia and Europe, as well as in Australia. Glufosinate-resistance genes have been introduced into over 20 crops, including rice, wheat, corn, sugar beets, tobacco, soybeans, cotton, potatoes, tomatoes, rapeseed, and sugarcane. Glufosinate has become the world's second-most-used genetically modified crop herbicide.

[0004] Glufosinate has two optical isomers, L-glufosinate and D-glufosinate, but only the L-configuration exhibits herbicidal activity. The D-configuration has virtually no herbicidal activity. L-glufosinate, also known as glufosinate-P, has twice the herbicidal activity of regular racemic glufosinate. Therefore, compared to D,L-glufosinate, the application rate of L-glufosinate is only 50% of that per acre, and the application costs of the two are essentially the same. Since glufosinate is typically available on the market as a racemic mixture of L-glufosinate and D-glufosinate, developing and producing a pure optical isomer of L-glufosinate would significantly reduce the amount of the herbicidal active ingredient required, which is crucial for improving product economics, reducing herbicide usage, and alleviating environmental pressures.

[0005] Currently, from the perspective of raw materials, the preparation methods of L-glufosinate can be divided into synthesis methods and separation methods. From the perspective of preparation methods, synthesis and separation methods can be further divided into biological methods and chemical methods, respectively.

[0006] Biosynthesis methods are mainly based on the ketoacid method, in which 2-oxo-4-(hydroxymethylphosphinyl)butyric acid (PPO) is used as a substrate to synthesize L-phosphinothricin through an amination reaction with transaminases or amino acid dehydrogenases. However, there are problems such as expensive raw materials, low conversion rate, complex system and difficult separation process, which make this method difficult to industrialize.

[0007] Chemical synthesis methods include chiral auxiliary methods, asymmetric catalytic methods, and chiral source methods. The auxiliary method uses expensive chiral auxiliary agents and has harsh reaction conditions. The asymmetric catalytic method uses expensive catalysts that are difficult to recover and recycle. Therefore, due to uncontrollable costs, this method is difficult to industrialize. The chiral source method uses expensive raw materials, has complex reaction steps, requires harsh reaction conditions and equipment requirements, produces many byproducts, and causes serious pollution. In short, chemical synthesis methods face challenges in the industrialization process.

[0008] Bioresolution methods involve ketoacid and acylation methods, both of which feature the involvement of enzymes, as described in US9834802 and CN108690854. However, these methods involve several enzymes and amine donors, leading to complex reaction systems, challenges in product purification, catalyst recycling, and the generation of high-phosphorus wastewater. Due to the overall cost challenges of industrialization, few commercial and industrial products are available on the market.

[0009] Chemical splitting method mainly relates to splitting the enantiomer of D, L- glufosinate or its salt with different chemical splitting agents, such as EP0499376A1, DE4407197A, EP16204249A, EP16204245A and CN112979701A, respectively disclose bromocamphorsulfonic acid, quinine (quinine), cinchonine (cinchonine), ephedrine (ephedrine) and ligand for splitting the purposes of the enantiomer of D, L- glufosinate. However, bromocamphorsulfonic acid, quinine and cinchonine are expensive, ephedrine is a controlled substance, and ligand is expensive, and reaction is complicated and metal wastewater stream is many. For these reasons, above-mentioned chemical splitting patent has not yet been successfully industrialized.

[0010] It can be seen that there is currently no efficient, green, simple separation process that can use D, L-glufosinate or its salt as raw material. Specifically, there is currently no such industrial method for obtaining L-glufosinate by chemical separation. Therefore, there is an urgent need for a low-cost, simple and industrially feasible L-glufosinate chemical separation process. Summary of the Invention

[0011] The present disclosure provides optically active glufosinate-lysine salts and preparation methods thereof. The optically active glufosinate-lysine salts include L-glufosinate-D-lysine salt, D-glufosinate-D-lysine salt, L-glufosinate-L-lysine salt and D-glufosinate-L-lysine salt.

[0012] The present disclosure relates to a method for producing an optically active glufosinate-lysine salt. The method comprises: a) mixing an enantiomeric mixture of D,L-glufosinate or a salt thereof, a resolving agent comprising optically active lysine, and a solvent to promote a resolution reaction, wherein the resolution reaction produces a resolution reaction mixture comprising the optically active glufosinate-lysine salt; b) crystallizing the glufosinate-lysine salt; and c) isolating the glufosinate-lysine salt from the resolution reaction mixture.

[0013] The optically active glufosinate-lysine salt is selected from the group consisting of L-glufosinate-D-lysine salt, D-glufosinate-D-lysine salt, L-glufosinate-L-lysine salt and D-glufosinate-L-lysine salt. In one embodiment, the resolving solvent for preparing D-glufosinate-D-lysine salt or L-glufosinate-L-lysine salt is an anhydrous system. In another embodiment, the resolving solvent for preparing L-glufosinate-D-lysine salt or D-glufosinate-L-lysine salt is an aqueous system.

[0014] L-phosphinothricin-D-lysine salt is a compound of formula I:

[0015]

[0016] D-phosphinothricin-D-lysine salt is a compound of formula II:

[0017]

[0018] L-phosphinothricin-L-lysine salt is a compound of formula III:

[0019]

[0020] D-phosphinothricin-L-lysine salt is a compound of formula IV:

[0021]

[0022] Other objects and features will be in part apparent and in part pointed out hereinafter. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The NMR of D-phosphinothricin-L-lysine salt (IV) prepared in Example 1 is depicted. 13 C.

[0024] Figure 2 The NMR of D-phosphinothricin-L-lysine salt (IV) prepared in Example 1 is depicted. 1 H.

[0025] Figure 3 The NMR of L-phosphinothricin-D-lysine salt (I) prepared in Example 3 is depicted. 13 C.

[0026] Figure 4 The NMR of L-phosphinothricin-D-lysine salt (I) prepared in Example 3 is depicted. 1 H.

[0027] Figure 5 The NMR of L-phosphinothricin-L-lysine salt (III) prepared in Example 4 is depicted. 13 C.

[0028] Figure 6 The NMR of L-phosphinothricin-L-lysine salt (III) prepared in Example 4 is depicted. 1 H.

[0029] Figure 7 The NMR of D-phosphinothricin-D-lysine salt (II) prepared in Example 5 is depicted. 13 C.

[0030] Figure 8 The NMR of D-phosphinothricin-D-lysine salt (II) prepared in Example 5 is depicted. 1 H.

[0031] Corresponding reference numerals indicate corresponding parts throughout the drawings. DETAILED DESCRIPTION

[0032] The present disclosure provides optically active amino acid salts and preparation methods thereof. The optically active amino acid salts include L-phosphinothricin-D-lysine salt, D-phosphinothricin-D-lysine salt, L-phosphinothricin-L-lysine salt and D-phosphinothricin-L-lysine salt.

[0033] The described L-phosphinothricin-D-lysine salt is a compound of formula I:

[0034]

[0035] The D-phosphinothricin-D-lysine salt described is a compound of formula II:

[0036]

[0037] The described L-phosphinothricin-L-lysine salt is a compound of formula III:

[0038]

[0039] The D-phosphinothricin-L-lysine salt described is a compound of formula IV:

[0040]

[0041] The present invention also provides a simple and feasible method for preparing optically active amino acid salts. The preparation method comprises: using D,L-phosphinothricin or its salt as a raw material, using D-lysine or L-lysine as a resolving agent, and obtaining L-phosphinothricin-D-lysine salt, D-phosphinothricin-D-lysine salt, L-phosphinothricin-L-lysine salt, and D-phosphinothricin-L-lysine salt by resolution reaction, crystallization, and filtration in a suitable resolving agent system. The main reaction equation is as follows:

[0042]

[0043] Glufosinate-ammonium and lysine can form a stable salt compound in a suitable solvent and crystallize into a solid to obtain an optically active glufosinate-ammonium-lysine salt.

[0044] Specifically, different solvent compositions have a significant effect on the optical activity of the formed glufosinate-lysine salt. In an anhydrous resolution system, when optically active lysine is used as a resolving agent, the separation yields D-glufosinate-D-lysine salt or L-glufosinate-L-lysine salt; in an aqueous resolution system, when optically active lysine is used as a resolving agent, the separation yields L-glufosinate-D-lysine salt or D-glufosinate-L-lysine salt. This surprising discovery has not been reported in any published literature.

[0045] Specifically, in an anhydrous resolution system, when L-lysine is used as a resolving agent, L-phosphinothricin-L-lysine salt (III) has a relatively low solubility and can be more easily crystallized, so what is obtained by the resolution is L-phosphinothricin-L-lysine salt (III). When D-lysine is used as a resolving agent, D-phosphinothricin-D-lysine salt (II) has a relatively low solubility and can be more easily crystallized, so what is obtained by the resolution is D-phosphinothricin-D-lysine salt (II).

[0046] In an aqueous resolution system, using L-lysine as a resolving agent, D-phosphinothricin-L-lysine salt (IV) has a lower solubility and is more easily crystallized, thereby splitting to obtain D-phosphinothricin-L-lysine salt (IV). Using D-lysine as a resolving agent, L-phosphinothricin-D-lysine salt (I) has a lower solubility and is more easily crystallized, thereby splitting to obtain L-phosphinothricin-D-lysine salt (I).

[0047] Optically active glufosinate-ammonium can be obtained from the resolved product or resolved mother liquor obtained by the present invention by methods well known to those skilled in the art. These methods may include filtration and centrifugation.

[0048] For example, D001 macroporous ion exchange resin can be used to separate L-phosphinothricin-D-lysine salt. First, the resin can be placed in a chromatography column, and the positive ions in the resin can be replaced with ammonium ions using a 5% ammonia solution. An aqueous solution containing an appropriate amount of L-phosphinothricin-D-lysine can be prepared, and a resin loaded with ammonium ions can be used for column chromatography. It is then washed with pure water to obtain a high-purity L-phosphinothricin aqueous solution, and then L-phosphinothricin can be obtained by crystallization. After washing with pure water, 5% ammonia solution can be used to wash off the D-lysine absorbed in the resin to obtain a D-lysine aqueous solution, and after crystallization, D-lysine can be obtained. The D-lysine obtained in this way can be used for the resolution reaction disclosed in this patent. The optical activity of the lysine obtained by column chromatography is unchanged, and has a high recovery rate.

[0049] The following are the preferred technical solutions for the preparation method of the present invention.

[0050] The mol ratio of L-configuration and D-configuration in the enantiomeric mixture of raw material D, L-glufosinate or its salt can be 0.25:1 to 4:1.When preparing L-glufosinate lysine amino acid salt (I and III) and the content of D-glufosinate or D-glufosinate salt in raw material is too high, splitting process can not make the salt crystallization of L-glufosinate well.The product obtained by splitting is still mainly D-glufosinate amino acid salt (II and IV), needs to make its multiple recrystallizations to obtain the product that is rich in I and III structure.In addition, operation is time-consuming, and productive rate is very low.Therefore, the raw material that is rich in D-configuration is not too suitable for preparing L-glufosinate lysine salt (I and III).Similarly, the raw material that is rich in L-configuration is not too suitable for preparing D-glufosinate lysine salt (II and IV).In addition, when the content of the single configuration of glufosinate in raw material is too high, the glufosinate product that is rich in described single configuration can be obtained by simple recrystallization, without the need to carry out splitting reaction. The molar ratio of the L-configuration to the D-configuration in the raw material D,L-glufosinate or its salt is further preferably 0.3:1 to 3:1.

[0051] In the preparation method, the resolving agent is optically active lysine, and in a suitable solvent system, D,L-phosphinothricin reacts with the corresponding optically active lysine to form an optically active glufosinate-lysine salt, which is further separated according to its solubility difference in the resolution system to obtain the corresponding optically active glufosinate-lysine salt.

[0052] D, the mol ratio of L-glufosinate or its salt and resolving agent lysine can be 1:0.2 to 1:2.When the amount of the optically active lysine for splitting is lower, product yield is low.When the amount of optically active lysine is larger, it can not significantly change the split result, and wastes resolving agent, increases the difficulty of post-processing, and causes unnecessary pollution.Therefore, the mol ratio of D, L-glufosinate or its salt and resolving agent lysine is further preferably 1:0.4 to 1:1.5.

[0053] In the preparation method, wherein the resolution reaction utilizes a resolution solvent, the resolution solvent may be a mixture of two or more solvents selected from the group consisting of: C1 to C4 monohydric or polyhydric alcohols, dimethylformamide, acetone, acetonitrile, methyl glycol, and water. The C1 to C4 monohydric or polyhydric alcohol may be one or more of: methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, ethylene glycol, propylene glycol, butylene glycol, or glycerol. The volume of water in the resolution solvent may be 0% to 70%.

[0054] Further preferably, the C1 to C4 monohydric alcohol or polyhydric alcohol is one or more of the following: methanol, ethanol, isopropanol, ethylene glycol or propylene glycol.

[0055] In the preparation of D-phosphinothricin-D-lysine salt or L-phosphinothricin-L-lysine salt, the resolution solvent may be an anhydrous system, preferably comprising one or more of the following: ethanol, isopropanol, methyl glycol, acetonitrile and dimethylformamide, and propylene glycol or glycerol.

[0056] In the preparation of L-phosphinothricin-D-lysine salt or D-phosphinothricin-L-lysine salt, the resolution solvent may be an aqueous system, preferably comprising one or more of the following: methanol, ethanol, isopropanol, tert-butanol, methyl glycol and acetone, as well as water.

[0057] In the preparation method, the volume of the water in the splitting solvent can be 0% to 70%. In an anhydrous system, the percentage of water is 0%. In an aqueous system, when the ratio of the water in the splitting solvent is high, the solubility of the two salts formed by D, L- glufosinate enantiomer and optically active lysine during the splitting process in the splitting solvent is relatively large, and the solubility difference is small. Therefore, the splitting effect is poor, and the splitting yield is extremely low, which is not suitable for splitting reaction. When the ratio of the water in the splitting solvent is low, as long as a suitable splitting solvent is selected, even if the volume of the water in the splitting solvent is very low, it still has a good splitting effect. The volume of the water in the splitting solvent is further preferably 0-50%.

[0058] In preparation method, the volume of splitting solvent can be 1mL-20mL / g starting material, that is, 1g D, L-grape phosphine-ammonium or its salt need 1mL-20mL to split solvent.When employed splitting solvent is lower than 1mL / g starting material, the solubility of the salt formed by the corresponding isomer of starting material and chiral amino acid is relatively low, and the optical purity of the product in crystalline solid is lower.When solvent volume is higher than 20mL / g starting material, the optical purity of crystalline product is better, but productive rate is extremely low.The volume of splitting solvent is further preferably 3mL-18mL / g starting material.

[0059] In the preparation method, the temperature of the resolution reaction can be 0-90°C. At higher temperatures, the difference in solubility of the salt formed by the enantiomer and the chiral amino acid is larger, and a product with high optical purity can be obtained. Under higher temperature conditions, the solubility of both is very high, but the yield is extremely low; at lower temperatures, the difference in solubility of the two is smaller, and the optical purity of the obtained product is poor. The resolution temperature of the resolution method is further preferably 15-65°C.

[0060] In the preparation method, adding seed crystals of the target product can accelerate the crystallization process; product crystals can also be obtained without adding corresponding seed crystals, but the crystallization time is much longer.

[0061] The present invention has the following advantages.

[0062] The L-glufosinate-D-lysine salt, D-glufosinate-D-lysine salt, L-glufosinate-L-lysine salt and D-glufosinate-L-lysine salt in the present invention are all optically active amino acid salts with stable properties. They can be separated from two amino acids by a simple method to obtain a single optically pure glufosinate (D-configuration or L-configuration), or glufosinate of different chiral purities can be prepared as needed.

[0063] The resolving agent used in the present invention is optically active lysine, and the raw material is widely available and inexpensive.

[0064] The method disclosed herein for preparing an optically active amino acid salt by resolution performed in the same resolution solvent system is simple to prepare and has strong operability, and can prepare L-glufosinate at a relatively low cost.

[0065] Having described the invention in detail, it will be apparent that modifications and variations are possible without departing from the scope of the invention as defined in the appended claims.

[0066] Examples

[0067] The following non-limiting examples are provided to further illustrate the present invention.

[0068] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only intended to illustrate the present invention and do not limit the scope of the present invention. After reading the present invention, various modifications made to the present invention in equivalent forms by those skilled in the art fall within the scope defined by the claims of the present invention.

[0069] Example 1

[0070] Under stirring, 40mL water is added to a 500mL three-necked flask. Then, 16.1g (0.11mol) L-lysine and D, L-phosphine ammonium 20g (0.11mol) are added in sequence, wherein D: L=50: 50, and the mixture is fully stirred until it is clarified. The temperature of the mixture is raised to above 50°C, and 200mL methanol is added. After fully stirring, stirring is continued, and the temperature of the mixture is raised to 60°C. After 2 hours, the temperature of the mixture is slowly cooled to 40°C while stirring for crystallization. After 60 hours of crystallization, the crystallized mixture is filtered while hot at 40°C, and the filtered solid is dried to obtain D-phosphine ammonium-L-lysine salt 14.1g, and yield is 39.1%, and HPLC analysis of D-phosphine ammonium optical purity is 84.6%.

[0071] 13 C NMR (126MHz, D2O) δ174.55,174.12,55.20,55.08,54.45,39.02,29.85,27.35,26.63,26.38,24.19,24.17,21.40,15.31,14.57.

[0072] 1 HNMR(500MHz,D2O)δ3.67(dt,J=18.8,6.2Hz,2H),2.96-2.89(m,2H),1.97(dtt,J=11.6,8.6,5.8Hz,2H),1.80 (dtd,J=9.6,6.2,3.3Hz,2H),1.68-1.61(m,1H),1.61-1.45(m,3H),1.45-1.27(m,2H),1.16(d,J=13.4Hz,3H).

[0073] Example 2

[0074] Under agitation, 50mL water is added into a 500mL three-necked flask.Then, 19.3g (0.13mol) L-lysine and 15.9g (0.088mol) D, L-phosphine ammonium are added successively, wherein D:L=58:42, and the mixture is fully stirred until it is clarified.The temperature of the mixture is raised to above 50 ℃, and 150mL methanol and 40mL ethanol are added.The mixture is fully stirred, and then maintained at 60 ℃ and continues to stir.After 2 hours, while stirring, the temperature of the mixture is slowly reduced to 40 ℃ for crystallization.After 30 hours, the mixture through crystallization is filtered while hot at 40 ℃, and the filtered solid is dried, to obtain D-phosphine ammonium-L-lysine salt 10.3g, productive rate is 36%, and HPLC analysis D-phosphine ammonium optical purity is 91.8%.

[0075] Example 3

[0076] Under stirring, 70mL water, 21.9g (0.15mol) D-lysine and 39.6g (0.2mol) D, L-glufosinate (wherein D: L=50: 50) are added in a 500mL three-necked flask. The mixture is fully stirred to dissolving and becomes clear. Then, 9mL ammonia is removed at 45 ℃ under-0.095MPa. The temperature of the mixture is maintained at 50 ℃, and 250mL methanol and 25mL isopropanol are added. The mixture is fully stirred. After stirring, 0.1g L-glufosinate-D-lysine salt (I) crystal is added, and the mixture is slowly cooled to room temperature and crystallized while stirring. After 15 hours of crystallization, the crystallized mixture is filtered at room temperature, and the filtered solid is dried, to obtain L-glufosinate-D-lysine salt 16.2g, productive rate is 33%, and HPLC analysis L-glufosinate optical purity is 94.2%.

[0077] 13 C NMR (126MHz, D2O) δ174.55,174.13,55.23,55.11,54.46,39.03,29.85,27.37,26.64,26.37,24.19,24.17,21.39,15.30,14.56.

[0078] 1HNMR(500MHz,D2O)δ3.73-3.63(m,2H),2.97-2.90(m,2H),2.05-1.93(m,2H),1.81(dtd,J=9.3,6.3,2 .6Hz,2H),1.64(dd,J=8.5,6.8Hz,2H),1.61-1.47(m,2H),1.47-1.30(m,2H),1.17(d,J=13.4Hz,3H).

[0079] Example 4

[0080] Under stirring, ethylene glycol 220mL is added to a 500mL three-necked flask. L-Lysine 30g (0.205mol) and D, L-phosphine ammonium 43.6g (0.24mol) are added sequentially, wherein D: L=40: 60. The temperature of the mixture is raised to dissolution until it is clarified, and maintained at 70°C. Ethanol 100mL is slowly added, and 0.1g L-phosphine ammonium-L-lysine salt (III) seed crystals are added. While stirring, the temperature is slowly lowered to 50°C for crystallization. After 20 hours, the mixture is filtered while hot at 50°C. The filter cake is washed with ethanol and dried to obtain L-phosphine ammonium L-lysine salt 28.2g, and yield is 42%, and HPLC analysis of L-phosphine ammonium optical purity is 90.2%.

[0081] 13 C NMR (126MHz, D2O) δ174.54,174.11,55.20,55.09,54.45,39.03,29.85,27.35,26.63,26.38,24.19,24.17,21.40,15.30,14.56.

[0082] 1 HNMR(500MHz,D2O)δ3.68(dt,J=18.9,6.0Hz,2H),2.93(t,J=7.6Hz,2H),1.98(dtt,J=10.6,8.6,6.0Hz,2H),1.81 (dtd,J=9.6,6.3,3.2Hz,2H),1.63(p,J=7.7Hz,2H),1.59-1.47(m,2H),1.47-1.27(m,3H),1.17(d,J=13.4Hz,3H).

[0083] Example 5

[0084] Under stirring, 75mL propylene glycol, 7.3g (0.05mol) D-lysine and 10g (0.055mol) D, L-glufosinate are added into a 250mL three-necked flask. The mixture is fully stirred to dissolving until it is clarified. The temperature of the mixture is maintained at 50 ℃. 16mL dimethylformamide is added, and the mixture is fully stirred. After stirring, 0.1g D-glufosinate-D-lysine salt (II) seed crystals are added, and the mixture is slowly cooled to room temperature for crystallization. After 8 hours of crystallization, the crystallized mixture is filtered at room temperature, and the filtered solid is dried, to obtain D-glufosinate-D-lysine salt 7.65g, productive rate is 46.8%, and the optical purity of obtaining D-glufosinate by HPLC analysis is 88.8%.

[0085] 13 C NMR (126MHz, D2O) δ174.53,174.09,55.18,55.07,54.44,39.02,29.84,27.34,26.61,26.37,24.18,24.16,21.40,15.29,14.55.

[0086] 1 HNMR(500MHz,D2O)δ3.68(dt,J=19.5,6.2Hz,2H),2.93(t,J=7.6Hz,2H),2.07-1.89(m,2H),1.81(dtd,J=9.6,6.2,3 .2Hz,2H),1.68-1.59(m,2H),1.52(dddd,J=25.3,14.6,10.8,5.9Hz,2H),1.46-1.28(m,2H),1.17(d,J=13.5Hz,3H).

[0087] Example 6

[0088] Under stirring conditions, 3.6L of water, 1.6kg of D-lysine and 2.2kg of D,L-glufosinate salt were added to a 20L reactor. Ammonia was removed under reduced pressure, and then 14.5L of methanol was added at 50°C. L-glufosinate-D-lysine crystals were added at 40°C, and the mixture was crystallized at 40°C while stirring. After 20 hours, the crystallized mixture was filtered while hot and dried to obtain 1.51kg of L-glufosinate-D-lysine salt with a yield of 42%, and an HPLC analysis of the L-glufosinate optical purity of 96.4%.

[0089] Example 7

[0090] Under agitation, 200mL water and 220g D-graft phosphine-L-lysine salt (optical purity D:L=79.1:20.9) are added in 2000mL reaction bottle.The temperature of mixture is raised to dissolving, until it clarifies, and at 60 DEG C, 1000mL methanol is added.Mixture is fully stirred and its crystallization is made.The mixture through crystallization is at room temperature filtered, and the filtered solid is dried, to obtain 155g D-graft phosphine-L-lysine salt, productive rate is 70.5%.Analyzed by HPLC, the optical purity of D-graft phosphine is 99.2%.

[0091] When introducing elements of the present invention or the preferred embodiments thereof, the articles "a," "an," and "the" are intended to mean that there are one or more of the elements. The terms "comprising," "including," and "having" are intended to be inclusive and mean that there may be additional elements other than the listed elements.

[0092] In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained.

[0093] As various changes could be made in the above products and methods without departing from the scope of the invention, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

Claims

1. A method for producing optically active glufosinate-lysine salt, the method comprising: a) mixing an enantiomeric mixture of D,L-glufosinate or a salt thereof, a resolving agent comprising optically active lysine, and a solvent to promote a resolution reaction, wherein the resolution reaction produces a resolution reaction mixture comprising an optically active glufosinate-lysine salt; b) crystallizing the glufosinate-lysine salt; and c) separating the glufosinate-lysine salt from the resolution reaction mixture. 2 . The method according to claim 1 , wherein the solvent is a mixture of two or more solvents selected from the group consisting of C1 to C4 monohydric or polyhydric alcohols, dimethylformamide, acetone, acetonitrile, methyl glycol, and water.

3. The method of claim 2, wherein the C1 to C4 monohydric or polyhydric alcohol is selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, tert-butanol, ethylene glycol, propylene glycol, butylene glycol, glycerol, and combinations thereof. The method according to claim 1 , wherein the solvent is an anhydrous solvent or an aqueous solvent.

5. The method of claim 4, wherein the solvent is anhydrous and comprises propylene glycol or glycerol and further comprises one or more of the following: ethanol, isopropyl alcohol, methyl glycol, acetonitrile, and dimethylformamide.

6. The method of claim 4, wherein the solvent is aqueous and comprises water and further comprises one or more of: methanol, ethanol, isopropanol, tert-butanol, methyl glycol, and acetone.

7. The method of any one of claims 1 to 6, wherein the molar ratio of L-glufosinate to D-glufosinate in the enantiomeric mixture of D,L-glufosinate or a salt thereof is from about 0.25:1 to about 4:

1.

8. The method of any one of claims 1 to 6, wherein the molar ratio of L-glufosinate to D-glufosinate in the enantiomeric mixture of D,L-glufosinate or a salt thereof is from about 0.3:1 to about 3:

1.

9. The method according to any one of claims 1 to 6, wherein the enantiomeric mixture of D,L-glufosinate or a salt thereof is racemic.

10. The method according to any one of claims 1 to 6, wherein the molar ratio of D,L-phosphinothricin or a salt thereof to the optically active lysine mixed in the resolution reaction mixture is about 1:0.2 to about 1:

2.

11. The method according to any one of claims 1 to 6, wherein the molar ratio of D,L-phosphinothricin or a salt thereof to the optically active lysine mixed in the resolution reaction mixture is about 1:0.4 to about 1:1.

5.

12. The method of any one of claims 1 to 6, wherein the volume of water in the solvent is 0% to about 70%.

13. The method of any one of claims 1 to 6, wherein the volume of water in the solvent is 0% to about 50%.

14. The method of any one of claims 1 to 6, wherein the solvent is mixed with the enantiomeric mixture of D,L-glufosinate or its salt in an amount of about 1 mL to about 20 mL per gram of D,L-glufosinate or its salt.

15. The method of any one of claims 1 to 6, wherein the solvent is mixed with the enantiomeric mixture of D,L-glufosinate or its salt in an amount of about 3 mL to about 18 mL per gram of D,L-glufosinate or its salt.

16. The process of any one of claims 1 to 6, wherein the temperature of the resolution reaction mixture is maintained at a temperature of about 0°C to about 90°C.

17. The process of any one of claims 1 to 6, wherein the temperature of the resolution reaction mixture is maintained at a temperature of about 15°C to about 65°C.

18. The method of any one of claims 1 to 6, wherein crystallizing the glufosinate-lysine salt comprises adding seed crystals of the optically active glufosinate-lysine salt.

19. The method of any one of claims 1 to 6, wherein separating the glufosinate-lysine salt from the resolution reaction mixture comprises filtration or centrifugation.

20. The method according to any one of claims 1 to 6, wherein the optically active glufosinate-lysine salt is selected from the group consisting of L-glufosinate-D-lysine salt, D-glufosinate-D-lysine salt, L-glufosinate-L-lysine salt and D-glufosinate-L-lysine salt.

21. The method according to any one of claims 1 to 4, wherein when the optically active glufosinate-lysine salt is D-glufosinate-D-lysine salt or L-glufosinate-L-lysine salt, the solvent is anhydrous, and when the optically active glufosinate-lysine salt is L-glufosinate-D-lysine or D-glufosinate-L-lysine, the solvent is aqueous.

22. The method of any one of claims 1 to 4, wherein the optically active glufosinate-lysine salt is L-glufosinate-D-lysine salt, the optically active lysine is D-lysine, and the solvent is aqueous.

23. The method of any one of claims 1 to 4, wherein the optically active glufosinate-lysine salt is D-glufosinate-D-lysine salt, the optically active lysine is D-lysine, and the solvent is anhydrous.

24. The method according to any one of claims 1 to 4, wherein the optically active glufosinate-lysine salt is L-glufosinate-L-lysine salt, the optically active lysine is L-lysine, and the solvent is anhydrous.

25. The method of any one of claims 1 to 4, wherein the optically active glufosinate-lysine salt is D-glufosinate-L-lysine salt, the optically active lysine is L-lysine, and the solvent is aqueous.

26. An optically active glufosinate-lysine salt selected from the group consisting of L-glufosinate-D-lysine salt, D-glufosinate-D-lysine salt, L-glufosinate-L-lysine salt and D-glufosinate-L-lysine salt.

27. The optically active glufosinate-lysine salt according to claim 26, wherein: The L-phosphinothricin-D-lysine salt is a compound of formula I: The D-phosphinothricin-D-lysine salt is a compound of formula II: The L-phosphinothricin-L-lysine salt is a compound of formula III: And the D-phosphinothricin-L-lysine salt is a compound of formula IV:

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