WO2024158883A1

WO2024158883A1 - Optically active amino acid salts and method for their preparation

Info

Publication number: WO2024158883A1
Application number: PCT/US2024/012729
Authority: WO
Inventors: Dihu Yu; Rick SHANG; Dapeng HOU; Yiwu QU; Quan Wang
Original assignee: Vulpes Agricultural Corp
Current assignee: Vulpes Agricultural Corp
Priority date: 2023-01-25
Filing date: 2024-01-24
Publication date: 2024-08-02
Anticipated expiration: 2025-07-25
Also published as: CN120677140A; EP4655280A1; AU2024213094A1

Abstract

The present invention discloses optically active glufosinate-lysine salts, with the structures of formulas (I – IV) shown below. The present invention also discloses a method of preparing the the optically active glufosinate-lysine salts, comprising using D,L-glufosinate or its salt as raw material, using D-lysine or L-lysine as the resolution agent, and obtaining L-glufosinate-D-lysine salt, D-glufosinate-D-lysine salt, L-glufosinate-L-lysine salt or D-glufosinate-L-lysine salt by resolution reaction, crystallization, and filtration in the suitable resolution agent system. D-glufosinate-D-lysine salt or L-glufosinate-L-lysine salt is prepared with the resolution solvent as an anhydrous system; and L-glufosinate-D-lysine salt or D-glufosinate-L-lysine salt is prepared with the resolution solvent as an aqueous system.

Description

OPTICALLY ACTIVE AMINO ACID SALTS AND METHOD FOR THEIR

PREPARATION

FIELD OF THE INVENTION

[0001] This disclosure involves 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. This disclosure also involves methods of preparing these salts from D,L-glufosinate and optically active lysine and use of these salts in agriculture to control unwanted plants, including in the propagation of transgenic crop plants.

BACKGROUND OF THE INVENTION

[0002] Glufosinate-ammonium, 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-ammonium belongs to the group of organophosphorus herbicides, which is one of the three major non-selective herbicides in the world. At present, the expanding global ban on paraquat, the continuing problem of glyphosate resistance, and the promotion of genetically modified technology are effectively driving the rapid increase of glufosinate demand. In recent years, glufosinate-resistant transgenic crops have been promoted and planted in select countries in Asia and Europe and in Australia, and the glufosinate resistant genes have been introduced into more than 20 crops including rice, wheat, com, sugar beet, tobacco, soybean, cotton, potato, tomato, rapeseed, and sugarcane. Glufosinate-ammonium has become the second largest transgenic crop herbicide in the world.

[0004] There are two optical isomers of glufosinate, L- and D-glufosinate, but only L-configuration has an herbicidal effect. D-configuration has almost no herbicidal activity. L-glufosinate, also known as glufosinate-P, has twice the herbicidal activity of common, racemic glufosinate. Thus, the application dosage is only 50% of glufosinate per acre for L-glufosinate compared to D, L-glufosinate, and the application cost is basically the same for both. Since glufosinate in the market is generally the racemate of L- and D- glufosinate, the development and production of pure optical isomers of L- glufosinate will greatly reduce the required amount of the herbicidal active ingredient, which is very important to improve the product economics, reduce the amount of herbicide use, and reduce environmental pressure.

[0005] At present, the preparation methods of L-glufosinate can be divided into synthetic methods and resolution methods from the perspective of raw materials. From the perspective of preparation means, the synthetic and resolution methods can be further divided into biological methods and chemical methods respectively.

[0006] The biological synthesis method is mainly based on the keto acid method, in which 2-oxo-4-(hydroxymethylphosphinyl)butyric acid (PPO) is used as the substrate to synthesize L-glufosinate by the amination reaction of transaminase or amino acid dehydrogenase. However, there are problems such as expensive raw materials, low conversion rate, complex system, and difficult separation process, which make the method difficult to industrialize.

[0007] The chemical synthesis method includes chiral auxiliary method, asymmetric catalytic method, and chiral source method. The auxiliary method uses expensive chiral auxiliaries, with demanding reaction conditions. The asymmetric catalytic method uses expensive catalysts, which are difficult to recover and recycle. Therefore, the method is difficult to industrialize because of uncontrollable costs. The chiral source method uses expensive raw materials, has complex reaction steps, requires demanding reaction conditions and equipment requirements, produces many byproducts, and causes serious pollution. In short, chemical synthesis methods all face challenges in industrialization.

[0008] The biological resolution method involves ketoacid and acylation methods, both featuring the involvement of biological enzymes, such as US9834802 and CN108690854. But the biological resolution method involves a few biological enzymes and amine donor, leading to complicated reaction systems, challenges in product purification, challenges in recycling the catalysts, production of high phosphorus content wastewater, among other problems. Due to challenges in overall industrialization cost, it is rare to see commercialized and industrialized products in large quantities on the market.

[0009] The chemical resolution method mainly involves the resolution of the enantiomeric isomers of D, L-glufosinate or its salts with different chemical resolution agents such as EP0499376A1, DE4407197A, EP16204249A, EP16204245A, and CN112979701 A, which respectively disclose the use of bromocamphorsulfonic acid, quinine, cinchonine, ephedrine, and ligands to resolve the enantiomeric isomers of D,L- glufosinate. However, bromocamphorsulfonic acid, quinine, and cinchonine are expensive, ephedrine is a controlled substance, and the ligands are costly with complicated reactions and heavy metal wastewater streams. For those reasons, the above chemical resolution patents have not been successfully industrialized.

[0010] It can be seen that there is still no efficient, green, and simple resolution process that can use D,L-glufosinate or its salts as raw material. In particular, there is no such industrial method to obtain L-glufosinate by chemical resolution. Thus, there is an urgent need for a low-cost, simple, and industrially feasible chemical resolution process of L-glufosinate.

BRIEF SUMMARY OF THE INVENTION

[0011] The present disclosure provides optically active, glufosinate-lysine salts and methods for their preparation. 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 disclosure is directed to a method of producing an optically active glufosinate-lysine salt. The method comprises a) mixing an enantiomeric mixture of D,L- glufosinate or its salt, a resolution agent comprising optically active lysine, and a solvent to facilitate a resolution reaction that produces a resolution reaction mixture comprising the optically active glufosinate-lysine salt; b) crystallizing the glufosinate-lysine salt; and c) separating 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 resolution solvent for the preparation of D-glufosinate-D-lysine salt or L-glufosinate-L-lysine salt is an anhydrous system. In another embodiment, the resolution solvent for the preparation of L-glufosinate-D-lysine salt or D-glufosinate-L-lysine salt is an aqueous system.

[0014] L-glufosinate-D-lysine salt is a compound of the structure of formula

[0015] D-glufosinate-D-lysine salt is a compound of the structure of formula I

[0016] L-glufosinate-L-lysine salt is a compound of the structure of formula I

[0017] D-glufosinate-L-lysine salt is a compound of the structure of formula

[0018] Other objects and features will be in part apparent and in part pointed out hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 depicts NMR ¹³C of D-glufosinate-L-lysine salt (IV) prepared in Example 1.

[0020] Figure 2 depicts NMR 'H of D-glufosinate-L-lysine salt (IV) prepared in Example 1.

[0021] Figure 3 depicts NMR ¹³C of L-glufosinate-D-lysine salt (I) prepared in Example 3;

[0022] Figure 4 depicts NMR 'H of L-glufosinate-D-lysine salt (I) prepared in Example 3.

[0023] Figure 5 depicts NMR ¹³C of L-glufosinate-L-lysine salt (III) prepared in Example 4.

[0024] Figure 6 depicts NMR 'H of L-glufosinate-L-lysine salt (III) prepared in Example 4.

[0025] Figure 7 depicts NMR ¹³C of D-glufosinate-D-lysine salt (II) prepared in Example 5.

[0026] Figure 8 depicts NMR 'H of D-glufosinate-D-lysine salt (II) prepared in Example 5. [0027] Corresponding reference characters indicate corresponding parts throughout the drawings.

DETAILED DESCRIPTION OF THE INVENTION

[0028] The present disclosure provides optically active amino acid salts and methods for their preparation. The optically active amino acid salts include L- glufosinate-D-lysine salt, D-glufosinate-D-lysine salt, L-glufosinate-L-lysine salt, and D- glufosinate-L-lysine salt.

[0029] The L-glufosinate-D-lysine salt described is a compound of the structure of formula

(I).

[0030] The D-glufosinate-D-lysine salt described is a compound of the structure of formula I

[0031] The L-glufosinate-L-lysine salt described is a compound of the structure of formula

[0032] The D-glufosinate-L-lysine salt described is a compound of the structure

[0033] The present invention also provides a simple and workable method for the preparation of optically active amino acid salts. The preparation method comprises: using D,L-glufosinate or its salt as raw material, using D-lysine or L-lysine as the resolution agent, and obtaining L-glufosinate-D-lysine salt, D-glufosinate-D-lysine salt,

L-glufosinate-L-lysine salt and D-glufosinate-L-lysine salt by resolution reaction, crystallization, and filtration in the suitable resolution agent system. The main reaction equations are as follows:

[0034] Glufosinate and lysine can form stable salt compounds in suitable solvents and crystallize as solids to obtain optically active glufosinate-lysine salts.

[0035] In particular, different solvent compositions have a significant effect on the optical activity of the formed glufosinate-lysine salts. In the anhydrous resolution system, with optically active lysine as the resolution agent, the resolution yields D- glufosinate-D-lysine salt or L-glufosinate-L-lysine salt; in the aqueous resolution system, with optically active lysine as the resolution agent, the resolution yields L-glufosinate-D- lysine salt or D glufosinate-L-lysine salt. This surprising finding has not been reported in any published literature.

[0036] Specifically, in the anhydrous resolution system, when L-lysine is used as the resolution agent, L-glufosinate-L-lysine salt (III) has lower solubility and can be crystallized more easily, so the resolution obtained is L-glufosinate-L-lysine salt (III). When D-lysine is used as the resolution agent, D-glufosinate-D-lysine salt (II) has lower solubility and can be crystallized more easily, so the resolution obtained is D- glufosinate-D-lysine salt (II). [0037] In the aqueous resolution system, using L-lysine as the resolution agent, D-glufosinate-L-lysine salt (IV) has lower solubility and crystallize more easily, so the resolution results in D-glufosinate-L-lysine salt (IV). Using D-lysine as the resolution agent, L-glufosinate-D-lysine salt (I) has lower solubility and crystallize more easily, so the resolution results in L-glufosinate-D-lysine salt (I).

[0038] The optically active glufosinate can be obtained from the resolution product or resolution mother liquor obtained by the present invention by methods well known to those skilled in the art. These methods can include filtration and centrifugation.

[0039] For example, one can use D001 macro-reticular type ion exchange resin to separate L-glufosinate-D-lysine salt. First, the resin can be put in the chromatography column, and 5% ammonia solution can be used to substitute the positive ions in the resin with ammonium ions. A water solution of a suitable amount of L-glufosinate-D-lysine can be prepared, and the ammonium ion loaded resin can be used for column chromatography. It can then be washed with pure water to obtain high-purity L- glufosinate-ammonium water solution, and then L-glufosinate-ammonium can be obtained through crystallization. After washing with pure water, 5% ammonia solution can be used to wash out the absorbed D-lysine in the resin to obtain a D-lysine water solution, and D-lysine can be obtained after crystallization. D-lysine obtained this way can be used in the resolution reaction disclosed in this patent. Lysine obtained through column chromatography does not change its optical activity and has a high rate of recovery.

[0040] The following is a preferred technical solution for the preparation method of the present invention.

[0041] The molar ratio of the L-configuration to the D-configuration in the enantiomeric mixture of the raw material D,L-glufosinate or its salt can be from 0.25: 1 to 4: 1. When L-glufosinate lysine amino acid salts (I and III) are prepared and the content of D-glufosinate or D-glufosinate salt in the raw material is too high, the resolution process cannot crystallize the salt of L-glufosinate well. The products obtained by resolution are still mostly D-glufosinate amino acid salts (II and IV), which need to be recrystallized several times to obtain the products rich in I and III structures. In addition, the operation is time consuming, and the yield is very low. Therefore, D-configuration- rich raw materials are less suitable for the preparation of L-glufosinate lysine salts (I and III). Similarly, L-configuration-rich raw materials are also less suitable for the preparation of D-glufosinate lysine salts (II and IV). Moreover, when the content of a single configuration of glufosinate in the raw material is too high, the product of glufosinate rich in the single configuiration can be obtained by simple recrystallization without the need of resolution reaction. The molar ratio of the L-configuration to the D- configuration in the raw material D,L-glufosinate or its salt is further preferred to be 0.3: 1 to 3:l.

[0042] In the preparation method, the resolution agent is optically active lysine, and in a suitable solvent system, D,L-glufosinate reacts with the corresponding optically active lysine to form optically active glufosinate-lysine salts, which are further separated according to their differences in solubility in the resolution system to obtain the corresponding optically active glufosinate-lysine salts.

[0043] The molar ratio of the D,L-glufosinate or its salt to the resolution agent lysine can be from 1 :0.2 to 1 :2. When the amount of optically active lysine used for resolution is low, the product yield is low. When the amount of optically active lysine is large, it does not significantly change the resolution result and wastes the resolution agent, increases the difficulty of post-treatment, and causes unnecessary pollution. Therefore, the molar ratio of D,L-glufosinate or its salt to the resolution agent lysine is further preferred to be 1 :0.4 to 1 : 1.5.

[0044] In the preparation method, wherein the resolution reaction utilizes a resolution solvent, the resolution solvent can be a mixture of two or more solvents selected from the group consisting of Ci to C4 mono- or polyols, dimethylformamide, acetone, acetonitrile, methyl ethylene glycol, and water. The Ci to C4 mono- or polyols can 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 can be from 0 to 70%.

[0045] Further preferably, the Ci to C4 mono-alcohol or polyol is one or more of methanol, ethanol, isopropanol, ethylene glycol, or propylene glycol.

[0046] In the preparation of the D-glufosinate-D-lysine salt or L-glufosinate-L- lysine salt, the resolution solvent can be an anhydrous system, preferably comprising one or more of ethanol, isopropanol, methyl ethylene glycol, acetonitrile, and dimethylformamide, and with propylene glycol or glycerol. [0047] In the preparation of the L-glufosinate-D-lysine salt or D-glufosinate-L- lysine salt, the resolution solvent can be an aqueous system, preferably comprising one or more of methanol, ethanol, isopropanol, tert-butanol, methyl ethylene glycol, and acetone with water.

[0048] In the preparation method, the volume of water in the resolution solvent can be from 0 to 70%. In the anhydrous system, the percentage of water is 0%. In the aqueous system, when the proportion of water in the resolution solvent is high, the solubility of both salts formed by D,L-glufosinate enantiomeric isomers and optically active lysine during the resolution process is relatively large in the resolution solvent, and the difference in solubility is small. Thus, the resolution effect is poor, and the resolution yield is extremely low, which is less suitable for the resolution reaction. When the proportion of water in the resolution solvent is low, as long as a suitable resolution solvent is selected, even if the volume of water in the resolution solvent is very low, it still has a good resolution effect. The volume of water in the resolution solvent is further preferred to be 0-50%.

[0049] In the preparation method, the volume of the resolution solvent can be lmL-20mL/g of raw material, i.e. 1g of D,L-glufosinate or its salt requires lmL-20mL of resolution solvent. When the used resolution solvent is lower than ImL/g of raw material, the solubility of the salt formed by the corresponding isomer of the raw material and the chiral amino acid is relatively low, and the optical purity of the product in the crystallized solid is low. When the solvent volume is higher than 20 mL/g of raw material, the optical purity of the crystallized product is better, but the yield is extremely low. The volume of the resolution solvent is further preferred to be 3mL-18mL/g of raw material.

[0050] In the preparation method, the temperature of the resolution reaction can be 0-90°C. At high temperature, the difference in solubility of the salt formed by the enantiomeric isomer and the chiral amino acid is large, and a product with high optical purity can be obtained. The solubility of both is high under high temperature conditions, but the yield is extremely low; at low temperature, the difference in solubility of both is small, and the product obtained has poor optical purity. The resolution temperature of the resolution method is further preferred to be 15-65°C. [0051] In the preparation method, the addition of the target product’s crystal seed can speed up the crystallization process; the product crystal can also be obtained without the addition of the corresponding crystal seed but with much longer crystallization time.

[0052] The present invention has the following advantages.

[0053] 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 optically active amino acid salts with stable properties, which can be separated from the two amino acids by a simple method to obtain a single optically pure glufosinate (D- configuration or L-configuration) or to prepare glufosinate of different chiral purity as needed.

[0054] The resolution agent used in the present invention is optically active lysine, and the raw material is widely available and inexpensive.

[0055] The method of the present disclosure for preparing optically active amino acid salts, using the resolution done in the same resolution solvent system, is simple to prepare and highly operative, and can prepare L-glufosinate at low cost.

[0056] Having described the invention in detail, it will be apparent that modifications and variations are possible without departing from the scope of the invention defined in the appended claims.

EXAMPLES

[0057] The following non-limiting examples are provided to further illustrate the present invention.

[0058] The present invention is further elucidated hereinafter in connection with specific embodiments, it being understood that these embodiments are intended only to illustrate the invention and not to limit the scope of the invention, and that after reading the invention, various modifications of the invention in equivalent form by those skilled in the art fall within the scope defined by the claims of the invention.

Example 1

[0059] Under stirring, 40mL of water was added to a 500mL three-necked flask. Then 16.1g (0.1 Imol) of L-lysine and D, L-glufosinate 20g (0.1 Imol), wherein D:L = 50:50, were added in turn, and the mixture was stirred thoroughly until it was clear. The temperature of the mixture was raised to above 50°C, and 200mL of methanol was added. After stirring thoroughly, the temperature of the mixture was raised to 60°C with continued stirring. After 2h, the temperature of the mixture was slowly cooled down to 40°C for crystallization while stirring. After 60h of crystallization, the crystallized mixture was filtered at 40°C while hot and the filtered solids were dried to obtain D- glufosinate-L-lysine salt 14.1g with a yield of 39.1% and HPLC analysis D-glufosinate optical purity of 84.6%.

[0060] ¹³C NMR (126 MHz, D₂O) 5 174.55, 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.

[0061] 'HNMR (500 MHz, D₂O) 5 3.67 (dt, J = 18.8, 6.2 Hz, 2H), 2.96 - 2.89 (m, 2H), 1.97 (dtt, J = 11.6, 8.6, 5.8 Hz, 2H), 1.80 (dtd, J = 9.6, 6.2, 3.3 Hz, 2H), 1.68 - 1.61 (m, 1H), 1.61 - 1.45 (m, 3H), 1.45 - 1.27 (m, 2H), 1.16 (d, J = 13.4 Hz, 3H).

Example 2

[0062] Under stirring, 50mL of water was added to a 500mL three-necked flask. Then, 19.3g (0.13mol) of L-lysine and 15.9g (0.088mol) of D,L-glufosinate, wherein D:L = 58:42, were added in turn, and the mixture was stirred thoroughly until it was clear. The temperature of the mixture was raised to above 50°C, and 150mL of methanol and 40mL of ethanol were added. The mixture was stirred thoroughly and then kept at 60°C with continued stirring. After 2h, the temperature of the mixture was slowly lowered to 40°C to crystallize while stirring. After 3 Oh, the crystallized mixture was filtered at 40°C while hot, and the filtered solids were dried to get D-glufosinate-L-lysine salt 10.3g with a yield of 36% and HPLC analysis D-glufosinate optical purity of 91.8%.

Example 3

[0063] Under stirring, 70mL of water, 21.9g (0.15mol) of D-lysine, and 39.6g (0.2mol) of D,L-glufosinate ammonium salt, where in D:L=50:50, were added to a 500mL three-necked flask. The mixture was stirred thoroughly to dissolve and become clear. Then, 9mL of ammonia was removed under -0.095MPa at 45°C. The temperature of the mixture was kept at 50°C, and 250mL of methanol and 25mL of isopropanol were added. The mixture was stirred thoroughly. After stirring, 0.1 g of L-glufosinate-D-lysine salt (I) crystal were added, and the mixture was slowly cooled down to room temperature for crystallization while stirring. After 15h crystallization, the crystallized mixture was filtered at room temperature, and the filtered solids were dried to obtain L-glufosinate-D- lysine salt 16.2g with a yield of 33% and HPLC analysis L-glufosinate optical purity of 94.2%.

[0064] ¹³C NMR (126 MHz, D₂O) 5 174.55, 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.

[0065] 'HNMR (500 MHz, D₂O) 5 3.73 - 3.63 (m, 2H), 2.97 - 2.90 (m, 2H), 2.05 - 1.93 (m, 2H), 1.81 (dtd, J = 9.3, 6.3, 2.6 Hz, 2H), 1.64 (dd, J = 8.5, 6.8 Hz, 2H), 1.61 - 1.47 (m, 2H), 1.47 - 1.30 (m, 2H), 1.17 (d, J = 13.4 Hz, 3H).

Example 4

[0066] Under stirring condition, ethylene glycol 220mL was added to a 500mL three-necked flask. L-lysine 30g (0.205mol) and D, L-glufosinate 43.6g (0.24mol), where in D:L=40:60, were added in turn. The temperature of the mixture was raised to dissolve until it was clear and kept at 70°C. Ethanol lOOmL was slowly added, and 0.1 g of L- glufosinate-L-lysine salt (III) crystal seed were added. The temperature was slowly lowered to 50°C to crystalize while stirring. After 20h, the mixture was filtered at 50°C while hot. The filtered cake was washed with ethanol and dried to obtain L-glufosinate L-lysine salt 28.2g with a yield of 42% and HPLC analysis L-glufosinate optical purity of 90.2%.

[0067] ¹³C NMR (126 MHz, D₂O) 5 174.54, 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.

[0068] 'HNMR (500 MHz, D₂O) 5 3.68 (dt, J = 18.9, 6.0 Hz, 2H), 2.93 (t, J = 7.6 Hz, 2H), 1.98 (dtt, J = 10.6, 8.6, 6.0 Hz, 2H), 1.81 (dtd, J = 9.6, 6.3, 3.2 Hz, 2H), 1.63 (p, J = 7.7 Hz, 2H), 1.59 - 1.47 (m, 2H), 1.47 - 1.27 (m, 3H), 1.17 (d, J = 13.4 Hz, 3H).

Example 5

[0069] Under stirring condition, 75mL of propylene glycol, 7.3g (0.05 mol) of D- lysine, and 10g (0.055 mol) of D, L-glufosinate were added to a 250mL three-necked flask. The mixture was stirred thoroughly to dissolve until it was clear. The temperature of the mixture was maintained at 50°C. 16mL of dimethylformamide was added, and the mixture was stirred thoroughly. After stirring, 0.1g of D-glufosinate-D-lysine salt (II) crystal seed were added, and the mixture was slowly cooled down to room temperature to crystallize. After 8h crystallization, the crystallized mixture was filtered at room temperature, and the filtered solids were dried to obtain D-glufosinate-D-lysine salt 7.65g with 46.8% yield and 88.8% optical purity of D-glufosinate by HPLC analysis.

[0070] ¹³C NMR (126 MHz, D₂O) 5 174.53, 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.

[0071] 'HNMR (500 MHz, D₂O) 5 3.68 (dt, J = 19.5, 6.2 Hz, 2H), 2.93 (t, J = 7.6 Hz, 2H), 2.07 - 1.89 (m, 2H), 1.81 (dtd, J = 9.6, 6.2, 3.2 Hz, 2H), 1.68 - 1.59 (m, 2H), 1.52 (dddd, J = 25.3, 14.6, 10.8, 5.9 Hz, 2H), 1.46 - 1.28 (m, 2H), 1.17 (d, J = 13.5 Hz, 3H).

Example 6

[0072] Under stirring condition, 3.6L of water, 1.6kg of D-lysine, and 2.2kg of D,L-glufosinate ammonium salt were added to a 20L reaction kettle. 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. The crystalized mixture was filtered while hot after 20h and dried to get 1.51 kg of L-glufosinate-D-lysine salt with a yield of 42% and HPLC analysis L- glufosinate optical purity of 96.4%

Example 7

[0073] Under stirring condition, 200 mL of water and 220 g of D-glufosinate-L- lysine salt (optical purity D:L=79.1 :20.9) was added to a 2000 mL reaction vial. The temperature of the mixture was raised to dissolve until it was clear, and 1000 mL of methanol was added at 60°C. The mixture was stirred thoroughly and crystallized. The crystallized mixture was filtered at room temperature, and the filtered solids were dried to obtain 155 g of D-glufosinate-L-lysine salt with a 70.5% yield. The optical purity of D-glufosinate was 99.2% by HPLC analysis.

[0074] When introducing elements of the present invention or the preferred embodiments(s) 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. [0075] In view of the above, it will be seen that the several objects of the invention are achieved, and other advantageous results attained.

[0076] 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

WHAT IS CLAIMED:

1. A method of producing an optically active glufosinate-lysine salt, the method comprising: a) mixing an enantiomeric mixture of D,L-glufosinate or its salt, a resolution agent comprising optically active lysine, and a solvent to facilitate a resolution reaction that 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 of claim 1, wherein the solvent is a mixture of two or more solvents selected from the group consisting of Ci to C4 mono- or polyols, dimethylformamide, acetone, acetonitrile, methyl ethylene glycol, and water.

3. The method of claim 2, wherein the Ci to C4 mono- or polyols are 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.

4. The method of claim 1, wherein the solvent is an anhydrous or 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 ethanol, isopropanol, methyl ethylene 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 ethylene 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 its salt 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 its salt is from about 0.3 : 1 to about 3: 1.

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

10. The method of any one of claims 1 to 6, wherein the molar ratio of D,L- glufosinate or its salt to the optically active lysine mixed in the resolution reaction mixture is from about 1 :0.2 to about 1 :2.

11. The method of any one of claims 1 to 6, wherein the molar ratio of D,L- glufosinate or its salt to the optically active lysine mixed in the resolution reaction mixture is from 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 from 0 to about 70%.

13. The method of any one of claims 1 to 6, wherein the volume of water in the solvent is from 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 from 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 from about 3 mL to about 18 mL per gram of D,L-glufosinate or its salt.

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

17. The method of any one of claims 1 to 6, wherein the temperature of the resolution reaction mixture is maintained at a temperature of from 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 a seed crystal 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 of 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 of any one of claims 1 to 4, wherein the solvent is anhydrous when the optically active glufosinate-lysine salt is D-glufosinate-D-lysine salt or L- glufosinate-L-lysine salt, and the solvent is aqueous when the optically active glufosinate-lysine salt is L-glufosinate-D-lysine or D-glufosinate-L-lysine.

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 of 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 of claim 26, wherein: the L-glufosinate-D-lysine salt is a compound of the structure of formula I:

the D-glufosinate-D-lysine salt is a compound of the structure of formula II:

the L-glufosinate-L-lysine salt is a compound of the structure of formula III:

; and the D-glufosinate-L-lysine salt is a compound of the structure of formula IV: