Chiral phosphoramide compound and application of chiral phosphoramide compound as agricultural bacteriostatic agent or in preparation of agricultural bacteriostatic agent

Abstract

The invention provides a chiral phosphoramide compound, which belongs to the technical field of organic synthesis technology and pesticide bacteriostatic activity research, and the structural general formula of the chiral phosphoramide compound is as shown in formula 1. The chiral phosphoramide compound has remarkable sterilization performance and has remarkable bacteriostatic activity on rice bacterial blight germs and rice leaf streak germs, and the chiral phosphoramide compound has important significance on further development and utilization of the chiral phosphoramide compound. The invention also provides an application of the chiral phosphoramide compound as an agricultural bacteriostatic agent or in preparation of the agricultural bacteriostatic agent.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis technology and pesticide antibacterial activity research, and particularly relates to a chiral phosphonamide compound and its application as or in the preparation of an agricultural antibacterial agent. Background Art

[0002] Phosphorus (V) chiral compounds are a unique and important class of compounds that exhibit a variety of biological activities, including anticancer (J.Med.Chem.2018,61,2211-2226) and antiviral (J.Med.Chem.2012.55,1196-2211) properties. Phosphamide compounds are widely used in the fields of medicine and agrochemicals due to their unique chemical properties. At the same time, phosphamide compounds are also widely used in the synthesis of ligands and catalysts. However, research on the use of catalyst control strategies to synthesize phosphamide compounds with high enantioselectivity has always been limited. In 2012, Zhang's group achieved the first synthesis of chiral phosphamide compounds by using chiral bicyclic imidazole catalysts (Tetrahedron:Asymmetry.2012,23,329-332). Recently, Miller and colleagues successfully constructed a series of chiral phosphamide compounds with high enantioselectivity through chiral phosphoric acid catalysis (Science 2021, 371, 702-707). In addition to these breakthroughs, there are still few catalytic methods for the high enantioselective synthesis of phosphamide compounds. In addition, phosphamide compounds are widely used in pesticides. Therefore, the efficient synthesis of chiral phosphamide compounds is of great research significance for the synthesis of agricultural fungicides. Summary of the invention

[0003] In order to obtain a series of new phosphamide compounds, the present invention provides a chiral phosphamide compound with higher enantioselectivity, and it is found that the chiral phosphamide compound has significant sterilization performance, which is of great significance to the further development and utilization of the chiral phosphamide compounds.

[0004] The present invention also provides an application of a chiral phosphamide compound as or in the preparation of an agricultural antibacterial agent.

[0005] The present invention is achieved through the following technical solutions:

[0006] The present invention provides a chiral phosphamide compound, the general structural formula of the chiral phosphamide compound is shown in Formula 1:

[0007]

[0008] In formula 1, the * phosphorus atom is a chiral phosphorus atom;

[0009] R 1Including any one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-methylphenyl, 4-phenylphenyl, 4-methoxyphenyl, 4-acetylphenyl, 3-chlorophenyl, 3-methoxyphenyl, 2-bromophenyl, 2-methoxyphenyl and methyl;

[0010] In formula 1, the sphere It includes any one of n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, allyl, phenyl, azetidinyl and tetrahydropyrrole.

[0011] Based on the same inventive concept, the present invention provides a method for preparing a chiral phosphamide compound, the preparation method comprising:

[0012] Mixing compound 1, benzoyl chloride, potassium carbonate, chiral catalyst C7 and toluene to obtain a mixture;

[0013] The mixture is reacted at a certain temperature for a period of time to obtain a reaction solution;

[0014] Adding 9-fluorenol to the reaction solution, stirring and reacting for a period of time to obtain a first mixed solution;

[0015] The first mixed solution is subjected to column chromatography and concentrated, and the obtained concentrated product is dissolved in carbon tetrachloride to obtain a second mixed solution;

[0016] Adding amine and triethylamine to the second mixed solution, reacting at a certain temperature for a period of time, to obtain a third mixed solution;

[0017] Purifying the third mixed solution to obtain a chiral phosphamide compound;

[0018] Wherein, the structural formula of the chiral catalyst C7 is shown in Formula 3:

[0019]

[0020] The structural formula of the compound 1 is as follows:

[0021]

[0022] R 1 The group includes any one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-methylphenyl, 4-phenylphenyl, 4-methoxyphenyl, 4-acetylphenyl, 3-chlorophenyl, 3-methoxyphenyl, 2-bromophenyl, 2-methoxyphenyl and methyl.

[0023] Further, the compound 1, benzoyl chloride, potassium carbonate, chiral catalyst C7 and toluene are mixed to obtain a mixture, specifically comprising:

[0024] Under an inert atmosphere, compound 1, benzoyl chloride, potassium carbonate, chiral catalyst C7 and toluene are mixed to obtain a mixture;

[0025] Wherein, the molar ratio of the compound 1, the benzoyl chloride and the potassium carbonate is 1:2:2;

[0026] The molar ratio of the chiral catalyst C7 to the compound 1 is 15:100.

[0027] Further, the mixture is reacted at a certain temperature for a period of time to obtain a reaction solution, which specifically includes:

[0028] The mixture was stirred at -10°C for 15 min to obtain a reaction solution.

[0029] Further, adding 9-fluorenol to the reaction solution and stirring the reaction for a period of time to obtain a first mixed solution specifically includes:

[0030] Add 9-fluorenol to the reaction solution, and stir the mixture at -10°C for 72 hours to obtain a first mixed solution;

[0031] The molar ratio of the 9-fluorenol to the compound 1 is 1.2:1.

[0032] Furthermore, the first mixed solution is subjected to column chromatography and concentrated, and the concentrated product is dissolved in carbon tetrachloride to obtain a second mixed solution, which specifically includes:

[0033] Using dichloromethane to perform column chromatography on the first mixed solution, and then concentrating under reduced pressure;

[0034] The obtained concentrated product is dissolved in carbon tetrachloride to obtain a second mixed solution.

[0035] Further, the step of adding amine and triethylamine to the second mixed solution and reacting them at a certain temperature for a period of time to obtain a third mixed solution specifically includes:

[0036] Adding amine and triethylamine to the second mixed solution, reacting at -20°C for 72 hours, to obtain a third mixed solution;

[0037] The molar ratio of the amine, the triethylamine and the compound 1 is 2:2:1.

[0038] Further, the third mixed solution is purified to obtain a chiral phosphamide compound, specifically comprising:

[0039] The third mixed solution is purified by silica gel column chromatography to obtain a chiral phosphamide compound.

[0040] Based on the same inventive concept, the present invention provides an application of a chiral phosphamide compound as or in the preparation of an agricultural antibacterial agent.

[0041] Based on the same inventive concept, the present invention provides a use of a chiral phosphamide compound as or in the preparation of an antibacterial agent for rice bacterial blight pathogen and / or rice leaf streak pathogen.

[0042] Based on the same inventive concept, the present invention provides an agricultural antibacterial agent, wherein the active ingredient of the agricultural antibacterial agent includes the above-mentioned chiral phosphamide compound.

[0043] One or more technical solutions in the embodiments of the present invention have at least the following technical effects or advantages:

[0044] 1. The present invention discloses a chiral phosphamide compound, which is prepared by using compound 1 and 9-fluorenol. The chiral phosphamide compound has good substrate universality, excellent yield (up to 87%), enantioselectivity (up to 98:2 e.r.) and significant biological activity. The prepared chiral phosphamide compound has excellent antibacterial activity and significant antibacterial activity against rice bacterial blight pathogen and rice leaf streak pathogen, and has important research significance for the further development and utilization of chiral phosphorus compounds.

[0045] 2. The present invention discloses a method for preparing a chiral phosphamide compound. The present invention uses phenylphosphinic acid and 9-alcohol under the catalysis of a thiourea small molecule catalyst C7 to construct a chiral phosphamide compound through an Atherton–Todd reaction. The substrate has good universality, excellent yield (up to 87%), and high enantioselectivity (up to 98:2 e.r.). The prepared chiral phosphamide compound has excellent antibacterial activity. The development of chiral phosphamide compounds provides a useful skeleton structure for future exploration of crop protection drugs, especially agricultural chemicals with antibacterial and antifungal activity, and has important research significance for the further development and utilization of chiral phosphamide compounds. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0047] Figure 1 The figure is a synthetic route diagram of the chiral phosphamide compounds of the present invention.

[0048] Figure 2 The synthetic route of compound 1 of the present invention is shown in FIG. DETAILED DESCRIPTION

[0049] The present invention will be described in detail below in conjunction with specific implementations and examples, and the advantages and various effects of the present invention will be more clearly presented. It should be understood by those skilled in the art that these specific implementations and examples are used to illustrate the present invention, rather than to limit the present invention.

[0050] Throughout the specification, unless otherwise specifically stated, the terms used herein should be understood as meanings commonly used in the art. Therefore, unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art to which the present invention belongs. In the event of a conflict, the present specification takes precedence.

[0051] Unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0052] The following is a detailed description of a chiral phosphonamide compound of the present application and its application as or in the preparation of an agricultural antibacterial agent in combination with examples and experimental data.

[0053] Example 1

[0054] This embodiment provides a method for preparing a chiral phosphamide compound, which is specifically as follows:

[0055] 1. Synthesis of Compound 1

[0056] like Figure 2 As shown, aniline (1.05 mol, 1.0 equiv.) was added dropwise to an aqueous solution of hypophosphorous acid (1.05 mol, 1.0 equiv.) at 0°C over 30 minutes through a dropping funnel. After the addition of aniline was completed, the light brown solution quickly turned into a thick slurry. After filtration, the off-white crystalline precipitate S1 was washed with cold acetone and used directly in the next step without further purification.

[0057] S1 (4.0 mmol, 2.0 equiv.), aryl iodobenzene (2.0 mmol, 1.0 equiv.), triethylamine (6.0 mmol, 3.0 equiv.), tetrakis(triphenylphosphine)palladium (0.04 mmol, 0.02 equiv.) were dissolved in acetonitrile or DMSO, and the reaction mixture was refluxed for 2-6 hours under good stirring. The reaction was monitored by TLC plate, and after completion of the reaction, it was filtered and evaporated under reduced pressure. H 2 O (20.0 mL), washed with ether (50 mL.). The aqueous phases were combined and acidified with aqueous potassium bisulfite. The resulting mixed solution was extracted with ethyl acetate (3 x 20.0 mL), anhydrous Na 2 SO 4 Drying and concentration were performed to obtain compound 1.

[0058] 2. Synthesis of chiral phosphamide compounds

[0059] like Figure 1 As shown, under nitrogen protection, compound 1 (0.1 mmol, 1.0 equiv.), benzoyl chloride (3a) (0.2 mmol, 2.0 equiv.), potassium carbonate (0.2 mmol, 2.0 equiv.), chiral catalyst C7 (15 mol%) and toluene (1.5 mL) were added to a 4.0 mL vial equipped with a magnetic stirrer. After the reaction mixture was stirred at -10 ° C for 15 minutes, 9-fluorenol (2d) (1.2 equiv.) was added to the system. The reaction was stirred at -10 ° C for 72 hours. Once the starting material was completely consumed by TLC detection, the resulting mixed solution was subjected to column chromatography on a 30 mm short silica gel column with dichloromethane (25.0 mL), and then the mixture was concentrated under reduced pressure. The resulting mixture was dissolved in 1.0 mL of carbon tetrachloride, followed by the addition of amine (2.0 equiv.) and triethylamine (2.0 equiv.). The reaction was reacted at -20 ° C for 72 hours. After the starting material was completely consumed, it was purified by silica gel column chromatography (petroleum ether:ethyl acetate=3:1) to obtain product 6-7.

[0060] The specific spectrum analysis of product 6-7 is as follows:

[0061] 9H-Fluoren-9-yl(S)-N-benzyl-P-phenylphosphonamidate(6d):

[0062]

[0063] 6d, white solid mp 159.1–160.9°C; 35.7 mg, 87% yield

[0064] 1 H NMR (400 MHz, CDCl 3 )δ7.89(ddd,J=13.1,8.3,1.4Hz,2H),7.70(dd,J=7.5,1.0Hz,1H),7.63(tt,J=7.7,0.9Hz,2H),7.55–7.48(m,2H),7.47–7.43(m,2H),7.41–7. 33(m,2H),7.41–7.33(m,2H),7.27(d,J=1.1Hz,2H),7.25–7.18(m,3H), 6.39(d,J=9.9Hz,1H),4.24–4.12(m,2H),3.33(dt,J=10.0,7.0Hz,1H).

[0065] 13 C NMR (101 MHz, CDCl 3 ) δ 142.5 (d, J = 4.0 Hz), 142.4 (d, J = 4.0 Hz), 140.6 (d, J = 22.2 Hz), 139.3 (d, J = 7.1 Hz), 132.1 (d, J = 3.0 Hz), 131.8 (d, J = 10.1 Hz), 131.6, 129.9, 129.4 (d, J = 9.1 Hz), 128.0 (d, J = 144.1 Hz), 127.8, 127.9 (d, J = 107.1 Hz), 126.2 (d, J = 27.3 Hz), 119.9 (d, J = 12.1 Hz), 76.1 (d, J = 6.1 Hz), 44.9.

[0066] 31 P NMR (162 MHz, CDCl 3 ) δ 24.3.

[0067] HRMS (ESI, m / z): Calculated for C 26 H 22 NNaO 2 P + [M + Na] + : 434.1280, found: 434.1269.

[0068] HPLC analysis: 98:2 e.r. (Chiralcel IA 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 8.0 min, Rt (minor) = 6.6 min.

[0069] 9H-Fluoren-9-yl (S)-N-benzyl-P-(4-fluorophenyl)phosphonamidate (6e):

[0070]

[0071] 6e, white solid m.p. 151.7–153.5 °C; 34.8 mg, 81% yield

[0072] 1 H NMR (400 MHz, CDCl 3)δ7.92–7.83(m,2H),7.69–7.63(m,3H),7.50(d,J=7.5Hz,1H),7.40(dd,J=13.8,6.2Hz,2H),7.31–7.27(m,2H),7.26–7.24(m,2H),7.23–7.21(m,2H),7.20–7.19(m,1H),7.12(td,J=8.7,3.0Hz,2H),6.40(d,J=9.8Hz,1H),4.24–4.11(m,2H),3.31–3.25(m,1H).

[0073] 13 C NMR(101MHz,CDCl 3 )δ142.4(d,J=4.0Hz),142.3(d,J=4.0Hz),140.6(d,J=22.2Hz),139.2(d,J=7.1Hz),134.6(d,J=21.2Hz),134.5(d,J=3.0Hz),129.5(d,J=7.1Hz),128.1(d,J=123.2Hz),127.9(d,J=3.0Hz),127.5,126.2(d,J=28.3Hz),120.0(d,J=12.1Hz),115.8(d,J=37.4Hz),115.6(d,J=5.1Hz),76.2(d,J=6.1Hz),45.0.

[0074] 31 P NMR(162MHz,CDCl 3 )δ23.2.

[0075] 19 F NMR(377MHz,CDCl 3 )δ-106.4.

[0076] HRMS(ESI,m / z):Calculated for C 26 H 21 FNNaO 2 P + [M+Na] + :452.1186,found:452.1203.

[0077]

[0078] HPLC analysis: 97:3 e.r. (Chiralcel IG 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 8.5 min, Rt (minor) = 9.7 min.

[0079] 9H-Fluoren-9-yl (S)-N-benzyl-P-(4-chlorophenyl)phosphonamidate (6f):

[0080]

[0081] 6f, white solid, m.p. 151.1–152.6 °C; 37.4 mg, 84% yield

[0082] 1 H NMR (400 MHz, CDCl 3 δ 7.83–7.77 (m, 2H), 7.69–7.63 (m, 3H), 7.51 (d, J = 7.5 Hz, 1H), 7.44–7.36 (m, 4H), 7.33–7.27 (m, 3H), 7.26–7.21 (m, 4H), 6.40 (d, J = 9.8 Hz, 1H), 4.23–4.09 (m, 2H), 3.31–3.22 (m, 1H).

[0083] 13 C NMR (101 MHz, CDCl 3 ) δ 142.3 (d, J = 3.0 Hz), 142.2 (d, J = 4.0 Hz), 140.6 (d, J = 24.2 Hz), 139.1 (d, J = 7.1 Hz), 138.7 (d, J = 7.1 Hz), 133.3 (d, J = 11.1 Hz), 130.4, 129.6 (d, J = 7.1 Hz), 128.8 (d, J = 15.2 Hz), 128.1 (d, J = 125.2 Hz), 127.9 (d, J = 5.1 Hz), 127.5, 126.2 (d, J = 27.3 Hz), 120.0 (d, J = 12.1 Hz), 76.3 (d, J = 6.1 Hz), 45.0.

[0084] 31 P NMR (162 MHz, CDCl 3 ) δ 23.0.

[0085] HRMS (ESI, m / z): Calculated for C 26 H 21 ClNNaO2 P + [M + Na] + : 468.0891, found: 468.1027.

[0086]

[0087] HPLC analysis: 96:4 e.r. (Chiralcel IG 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 9.9 min, Rt (minor) = 11.0 min.

[0088] 9H-Fluoren-9-yl (S)-N-benzyl-P-(4-bromophenyl)phosphonamidate (6 g):

[0089]

[0090] 6 g, white solid m.p. 152.6–154.2 °C; 39.6 mg, 81% yield

[0091] 1 H NMR (400 MHz, CDCl 3 ) δ 7.75–7.70 (m, 2H), 7.66 (q, J = 7.7, 7.3 Hz, 3H), 7.58 (dd, J = 8.3, 3.2 Hz, 2H), 7.51 (d, J = 7.5 Hz, 1H), 7.43–7.36 (m, 2H), 7.31–7.27 (m, 2H), 7.26–7.24 (m, 4H), 7.24–7.21 (m, 2H), 6.40 (d, J = 9.8 Hz, 1H), 4.23–4.09 (m, 1H), 3.29–3.23 (m, 1H).

[0092] 13 C NMR (101 MHz, CDCl 3)δ 142.3 (d, J = 3.0 Hz), 142.4 (d, J = 4.0 Hz), 140.6 (d, J = 24.2 Hz), 139.1 (d, J = 7.1 Hz), 133.4 (d, J = 11.1 Hz), 131.8 (d, J = 15.2 Hz), 130.0 (d, J = 175.7 Hz), 129.6 (d, J = 7.1 Hz), 128.1 (d, J = 125.2 Hz), 127.9 (d, J = 6.1 Hz), 127.5, 127.2 (d, J = 4.0 Hz), 126.2 (d, J = 27.3 Hz), 120.0 (d, J = 12.1 Hz), 76.3 (d, J = 5.1 Hz), 45.0.

[0093] 31 P NMR (162 MHz, CDCl 3 )δ 23.1.

[0094] HRMS (ESI, m / z): Calculated for C 26 H 21 BrNNaO 2 P + [M + Na] + : 512.0385, found: 512.0377.

[0095]

[0096] HPLC analysis: 95:5 e.r. (Chiralcel ID 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 11.1 min, Rt (minor) = 12.3 min.

[0097] 9H-Fluoren-9-yl (S)-N-benzyl-P-(4-(trifluoromethyl)phenyl)phosphonamidate (6h):

[0098]

[0099] 6h, white solid m.p. 149.8–151.4 °C; 40.2 mg, 84% yield

[0100] 1 H NMR (400 MHz, CDCl 3)δ7.97(dd,J=12.7,7.9Hz,2H),7.71–7.66(m,1H),7.65–7.64(m,2H),7.63(t,J=6.1Hz,2H),7.54(d,J=7.5Hz,1H),7.44–7.37(m,2H),7.31–7.28(m,2H),7.27–7.25(m,3H),7.24–7.22(m,2H),6.43(d,J=9.7Hz,1H),4.25–4.11(m,2H),3.31(q,J=7.8Hz,1H).

[0101] 13 C NMR(101MHz,CDCl 3 )δ142.1(d,J=4.0Hz),140.7(d,J=29.3Hz),138.9(d,J=7.1Hz),134.6,133.9,133.6,132.2(d,J=10.1Hz),129.7(d,J=7.1Hz),128.1(d,J=129.3Hz),127.9(d,J=9.1Hz),127.6,126.2(d,J=30.3Hz),125.4(d,J=3.0Hz),125.3(d,J=4.0Hz),120.1(d,J=14.1Hz),76.5(d,J=6.1Hz),45.1.

[0102] 31 P NMR(162MHz,CDCl 3 )δ21.6.

[0103] 19 F NMR(377MHz,CDCl 3 )δ-63.2.

[0104] HRMS(ESI,m / z):Calculated for C 27 H 21 F 3 NNaO 2 P + [M+Na] + :502.1154,found:502.1157.

[0105]

[0106] HPLC analysis: 96:4 e.r. (Chiralcel IG 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 6.6 min, Rt (minor) = 7.7 min.

[0107] 9H-Fluoren-9-yl (S)-N-benzyl-P-(4-cyanophenyl)phosphonamidate (6i):

[0108]

[0109] 6i, white solid, m.p. 156.7–157.2 °C; 34.5 mg, 79% yield

[0110] 1 H NMR (400 MHz, CDCl 3 ) δ 7.91 (dd, J = 12.9, 8.2 Hz, 2H), 7.69 (d, J = 3.3 Hz, 1H), 7.68–7.63 (m, 3H), 7.62–7.61 (m, 1H), 7.54 (d, J = 7.5 Hz, 1H), 7.44–7.37 (m, 2H), 7.30 (dd, J = 5.4, 3.3 Hz, 1H), 7.27–7.26 (m, 2H), 7.25–7.23 (m, 2H), 7.24–7.20 (m, 2H), 6.42 (d, J = 9.7 Hz, 1H), 4.24–4.11 (m, 2H), 3.42–3.36 (m, 1H).

[0111] 13 C NMR (101 MHz, CDCl 3 ) δ 141.9 (d, J = 3.0 Hz), 141.8 (d, J = 5.1 Hz), 140.7 (d, J = 30.3 Hz), 138.7 (d, J = 7.1 Hz), 136.6 (d, J = 172.7 Hz), 132.2 (d, J = 9.1 Hz), 132.0 (d, J = 14.1 Hz), 130.0 (d, J = 7.1 Hz), 128.1 (d, J = 131.3 Hz), 128.0 (d, J = 10.1 Hz), 127.7, 126.2 (d, J = 35.4 Hz), 120.1 (d, J = 14.1 Hz), 118.0, 115.5 (d, J = 3.0 Hz), 76.6 (d, J = 6.1 Hz), 45.1.

[0112] 31 P NMR (162 MHz, CDCl3 ) δ 20.7.

[0113] HRMS(ESI, m / z): Calculated for C 27 H 21 N 2 NaO 2 P + [M + Na] + : 459.1233, found: 459.1231.

[0114]

[0115] HPLC analysis: 88:12 e.r. (Chiralcel ID40: 60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt(major) = 8.7 min, Rt(minor) = 9.4 min.

[0116] 9H-Fluoren-9-yl (S)-N-benzyl-P-(p-tolyl)phosphonamidate (6j):

[0117]

[0118] 6j, white solid m.p. 124.7–126.1 °C; 34.0 mg, 80% yield

[0119] 1 H NMR (400 MHz, CDCl 3 ) δ 7.78 (dd, J = 12.9, 8.1 Hz, 2H), 7.72 (dd, J = 7.4, 1.0 Hz, 1H), 7.65–7.61 (m, 2H), 7.50 (dd, J = 7.5, 1.0 Hz, 1H), 7.42–7.33 (m, 2H), 7.29–7.28 (m, 2H), 7.27 (s, 1H), 7.25–7.24 (m, 3H)), 7.23–7.21 (m, 2H), 7.20–7.18 (m, 1H), 6.37 (d, J = 9.9 Hz, 1H), 4.23–4.09 (m, 2H), 3.29–7.27 (m, 1H), 2.39 (s, 3H).

[0120] 13 C NMR (101 MHz, CDCl 3)δ142.7(d,J = 2.0Hz), 142.6(d,J = 6.1Hz), 140.6(d,J = 20.2Hz), 139.5(d,J = 7.1Hz), 132.0(d,J = 10.1Hz), 129.3(d,J = 1.4Hz), 129.4(d,J = 24.4Hz), 128.3, 128.0(d,J = 111.1Hz), 127.8(d,J = 2.0Hz), 127.3, 126.6, 126.3(d,J = 23.2Hz), 119.9(d,J = 11.1Hz), 76.0(d,J = 6.1Hz), 44.9, 21.6(d,J = 2.0Hz).

[0121] 31 P NMR(162MHz, CDCl 3 )δ25.0.

[0122] HRMS(ESI, m / z): Calculated for C 27 H 24 NNaO 2 P + [M + Na] + : 448.1437, found: 448.1434.

[0123]

[0124] HPLC analysis: 97:3 e.r. (Chiralcel IG 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt(major) = 7.9 min, Rt(minor) = 16.7 min.

[0125] 9H-Fluoren-9-yl (S)-P-([1,1'-biphenyl]-4-yl)-N-benzylphosphonamidate(6k):

[0126]

[0127] 6k, white solid m.p. 177.3–178.6 °C; 41.9 mg, 86% yield

[0128] 1 H NMR(400MHz, CDCl 3)δ7.95(dd,J=12.8,8.2Hz,2H),7.73(dd,J=7.5,1.0Hz,1H),7.68–7.67(m,1H),7.66(d,J=1.6Hz,1H),7.63(d,J=7.7Hz,2H),7.61–7.58(m,2H),7.56(dd,J=7.5,1.0Hz,1H),7.48–7.43(m,2H),7.40(ddd,J=8.0,6.6,1.5Hz,2H),7.35(dd,J=7.5,1.2Hz,1H),7.29(d,J=1.7Hz,3H),7.28–7.23(m,3H),7.22–7.20(m,1H),6.43(d,J=9.9Hz,1H),4.28–4.14(m,2H),3.40–3.34(m,1H).

[0129] 13 C NMR(101MHz,CDCl 3 )δ144.8(d,J=3.0Hz),142.5(d,J=4.0Hz),142.3(d,J=4.0Hz),140.6(d,J=22.2Hz),140.0,139.4(d,J=7.1Hz),132.4(d,J=9.1Hz),130.3,129.4(d,J=8.1Hz),128.8(d,J=32.3Hz),128.1,127.8(d,J=3.0Hz),127.5,127.4(d,J=24.2Hz),127.2,127.1,126.3(d,J=28.3Hz),119.9(d,J=12.1Hz),76.1(d,J=6.1Hz),45.0.

[0130] 31 P NMR(162MHz,CDCl 3 )δ24.4.

[0131] HRMS(ESI,m / z):Calculated for C 32 H 26 NNaO 2 P + [M+Na] + :510.1593,found:510.1580.

[0132]

[0133] HPLC analysis: 98:2 e.r. (Chiralcel IA 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 7.4 min, Rt (minor) = 6.8 min.

[0134] 9H-Fluoren-9-yl (S)-N-benzyl-P-(4-methoxyphenyl)phosphonamidate (6l):

[0135]

[0136] 6l, white solid, m.p. 158.1–159.4 °C; 37.5 mg, 85% yield

[0137] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.87–7.81 (m, 2H), 7.74–7.72 (m, 1H), 7.64 (td, J = 7.7, 0.9 Hz, 2H), 7.49–7.46 (m, 1H), 7.41–7.34 (m, 2H), 7.29 (d, J = 0.9 Hz, 2H), 7.28–7.25 (m, 3H), 7.24–7.19 (m, 2H), 6.99–6.94 (m, 2H), 6.37 (d, J = 10.0 Hz, 1H), 4.24–4.09 (m, 2H), 3.85 (s, 3H), 3.15 (s, 1H).

[0138] 13 13C NMR (101 MHz, CDCl 3 ) δ 162.7 (d, J = 3.0 Hz), 142.7 (d, J = 5.1 Hz), 142.6 (d, J = 4.0 Hz), 140.6 (d, J = 17.2 Hz), 139.5 (d, J = 8.1 Hz), 133.9 (d, J = 11.1 Hz), 129.4 (d, J = 8.1 Hz), 128.0 (d, J = 113.1 Hz), 127.8 (d, J = 3.0 Hz), 127.4, 126.3 (d, J = 18.2 Hz), 121.9 (d, J = 179.8 Hz), 119.9 (d, J = 10.1 Hz), 114.0 (d, J = 15.2 Hz), 76.0 (d, J = 6.1 Hz), 55.3, 44.9.

[0139] 31 31P NMR (162 MHz, CDCl 3 ) δ 25.0.

[0140] HRMS(ESI, m / z): Calculated for C 27 H 24 NNaO 3 P + [M + Na] + : 464.1386, found: 464.1383.

[0141]

[0142] HPLC analysis: 95:5 e.r. (Chiralcel IA 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt(major) = 8.0 min, Rt(minor) = 7.4 min.

[0143] 9H-Fluoren-9-yl (S)-N-benzyl-P-(4-formylphenyl)phosphonamidate(6m):

[0144]

[0145] 6m, white solid m.p. 141.5–142.6 °C; 38.5 mg, 85% yield

[0146] 1 H NMR(400 MHz, CDCl 3 ) δ 7.99–7.97 (m, 3H), 7.96–7.94 (m, 1H), 7.70–7.63 (m, 3H), 7.55–7.52 (m, 1H), 7.43–7.35 (m, 2H), 7.32–7.27 (m, 2H), 7.26–7.24 (m, 3H), 7.23–7.21 (m, 2H), 6.42 (d, J = 9.7 Hz, 1H), 4.21–4.14 (m, 2H), 3.39–3.33 (m, 1H), 2.62 (s, 3H).

[0147] 13 C NMR(101 MHz, CDCl 3) δ 197.6, 142.2 (d, J = 4.0 Hz), 140.6 (d, J = 27.3 Hz), 139.5 (d, J = 3.0 Hz), 139.0 (d, J = 7.1 Hz), 136.0 (d, J = 171.7 Hz), 132.1 (d, J = 10.1 Hz), 129.6 (d, J = 8.1 Hz), 128.2, 128.0 (d, J = 126.3 Hz), 127.9 (d, J = 8.1 Hz), 127.9, 127.5, 126.2 (d, J = 26.3 Hz), 120.0 (d, J = 12.1 Hz), 76.3 (d, J = 6.1 Hz), 45.0, 26.8.

[0148] 31 P NMR (162 MHz, CDCl 3 ) δ 22.3.

[0149] HRMS (ESI, m / z): Calculated for C 28 H 24 NNaO 3 P + [M + Na] + : 476.1386, found: 476.1389.

[0150]

[0151] HPLC analysis: 97:3 e.r. (Chiralcel IB 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 9.1 min, Rt (minor) = 16.2 min.

[0152] 9H-Fluoren-9-yl (S)-N-benzyl-P-(3-chlorophenyl)phosphonamidate (6n):

[0153]

[0154] 6n, white solid m.p. 141.5–142.7 °C; 37.4 mg, 84% yield

[0155] 1 H NMR (400 MHz, CDCl 3)δ7.83(dt,J=13.5,1.8Hz,1H),7.73(ddt,J=12.7,7.5,1.3Hz,1H),7.69–7.60(m,3H),7.54(dd,J=7.5,1.0Hz,1H),7.50–7.47(m,1H),7.41(dd,J=7.5,1.1Hz,1H),7.39–7.34(m,2H),7.28(d,J=1.4Hz,1H),7.27(d,J=1.7Hz,3H),7.26–7.22(m,3H),6.40(d,J=9.8Hz,1H),4.25–4.09(m,2H),3.38–3.32(m,1H).

[0156] 13 C NMR(101MHz,CDCl 3 )δ142.2(d,J=2.0Hz),142.1(d,J=2.0Hz),140.6(d,J=26.3Hz),139.1(d,J=7.1Hz),134.8(d,J=19.2Hz),133.3(d,J=173.7Hz),132.2(d,J=3.0Hz),131.7(d,J=11.1Hz),129.9(d,J=25.3Hz),129.8,129.6(d,J=7.1Hz),128.1(d,J=122.2Hz),127.9(d,J=9.1Hz),127.5,126.2(d,J=32.3Hz),120.0(d,J=13.1Hz),76.3(d,J=6.1Hz),45.0.

[0157] 31 P NMR(162MHz,CDCl 3 )δ22.0.

[0158] HRMS(ESI,m / z):Calculated for C 26 H 21 ClNNaO 2 P + [M+Na] + :468.0891,found:468.0895.

[0159]

[0160] HPLC analysis: 97:3 e.r. (Chiralcel IA 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 7.1 min, Rt (minor) = 6.1 min.

[0161] 9H-Fluoren-9-yl (S)-N-benzyl-P-(3-methoxyphenyl)phosphonamidate (6o):

[0162]

[0163] 6o, white solid, m.p. 116.7–118.5 °C; 36.6 mg, 83% yield

[0164] 1 H NMR (400 MHz, CDCl 3 ) δ 7.72 (dd, J = 7.5, 1.0 Hz, 1H), 7.64 (tt, J = 7.5, 0.9 Hz, 2H), 7.51–7.44 (m, 2H), 7.43–7.40 (m, 1H), 7.39–7.34 (m, 3H), 7.29 (dd, J = 3.4, 1.1 Hz, 2H), 7.28–7.25 (m, 3H), 7.25–7.19 (m, 2H), 7.08–7.05 (m, 1H), 6.40 (d, J = 9.9 Hz, 1H), 4.26–4.15 (m, 2H), 3.78 (s, 3H), 3.23–3.17 (m, 1H).

[0165] 13 C NMR (101 MHz, CDCl 3 ) δ 159.5 (d, J = 18.2 Hz), 142.5 (d, J = 4.0 Hz), 142.4 (d, J = 5.1 Hz), 140.6 (d, J = 19.2 Hz), 139.3 (d, J = 7.1 Hz), 132.9, 131.2, 129.8 (d, J = 17.2 Hz), 129.5 (d, J = 8.1 Hz), 128.0 (d, J = 115.1 Hz), 127.8 (d, J = 2.0 Hz), 126.3 (d, J = 24.2 Hz), 124.1 (d, J = 9.1 Hz), 119.9 (d, J = 11.1 Hz), 118.6 (d, J = 3.0 Hz), 116.4 (d, J = 12.1 Hz), 76.2 (d, J = 5.1 Hz), 55.4, 44.9.

[0166] 31P NMR (162 MHz, CDCl 3 ) δ 24.1.

[0167] HRMS (ESI, m / z): Calculated for C 27 H 24 NNaO 3 P + [M + Na] + : 464.1386, found: 464.1400.

[0168]

[0169] HPLC analysis: 94:6 e.r. (Chiralcel IC 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 14.9 min, Rt (minor) = 13.6 min.

[0170] 9H-Fluoren-9-yl (S)-N-benzyl-P-(2-bromophenyl)phosphonamidate (6p):

[0171]

[0172] 6p, white solid, m.p. 141.5–142.8 °C; 41.6 mg, 85% yield

[0173] 1 H NMR (400 MHz, CDCl 3 ) δ 8.18–8.09 (m, 1H), 7.72 (ddd, J = 9.1, 7.7, 1.1 Hz, 2H), 7.65 (dt, J = 3.9, 2.1 Hz, 1H), 7.64–7.61 (m, 2H), 7.41–7.37 (m, 2H), 7.37–7.30 (m, 3H), 7.29–7.27 (m, 2H), 7.27–7.25 (m, 2H), 7.24–7.19 (m, 2H), 6.44 (d, J = 9.9 Hz, 1H), 4.31–4.18 (m, 2H), 3.78–3.72 (m, 1H).

[0174] 13 C NMR (101 MHz, CDCl 3)δ142.2(d, J = 2.0Hz), 142.1(d, J = 2.0Hz), 140.6(d, J = 30.3Hz), 139.3(d, J = 7.1Hz), 136.0(d, J = 7.1Hz), 134.0(d, J = 10.1Hz), 133.2(d, J = 2.0Hz), 131.9(d, J = 175.7Hz), 129.5(d, J = 6.1Hz), 128.0(d, J = 106.1Hz), 127.8(d, J = 14.1Hz), 127.3, 127.2(d, J = 13.1Hz), 126.6(d, J = 47.5Hz), 124.7(d, J = 5.1Hz), 119.9(d, J = 17.2Hz), 76.3(d, J = 6.1Hz), 45.25.

[0175] 31 P NMR(162MHz, CDCl 3 )δ20.3.

[0176] HRMS(ESI, m / z): Calculated for C 26 H 21 BrNNaO 2 P + [M + Na] + : 512.0385, found: 512.0390.

[0177]

[0178] HPLC analysis: 95:5 e.r. (Chiralcel IG 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt(major) = 10.5 min, Rt(minor) = 15.9 min.

[0179] 9H-Fluoren-9-yl (S)-N-benzyl-P-(2-methoxyphenyl)phosphonamidate(6q):

[0180]

[0181] 6q, white solid, m.p. 139.1–140.5 °C; 36.2 mg, 82% yield

[0182] 1 H NMR(400MHz, CDCl 3)δ8.04(ddd,J=14.5,7.5,1.8Hz,1H),7.81–7.78(m,1H),7.64–7.60(m,2H),7.54–7.49(m,1H),7.43–7.37(m,2H),7.36–7.32(m,1H),7.31–7.28(m,2H),7.27–7.25(m,2H),7.24–7.23(m,1H),7.23–7.19(m,2H),7.09–7.05(m,1H),7.00–6.92(m,1H),6.29(d,J=11.0Hz,1H),4.33(ddd,J=9.2,6.8,2.2Hz,2H),3.82(s,3H),3.63–3.59(m,1H).

[0183] 13 C NMR(101MHz,CDCl 3 )δ160.1(d,J=3.0Hz),142.8(d,J=4.0Hz),142.7(d,J=5.1Hz),140.6(d,J=10.1Hz),140.3(d,J=7.1Hz),134.6(d,J=7.1Hz),133.9(d,J=2.0Hz),129.2(d,J=7.1Hz),128.4,127.5,127.7(d,J=5.1Hz),127.1,126.2(d,J=4.0Hz),120.9(d,J=13.1Hz),119.8(d,J=7.1Hz),110.9(d,J=9.1Hz),75.8(d,J=6.1Hz),55.7,44.9.

[0184] 31 P NMR(162MHz,CDCl 3 )δ23.2

[0185] HRMS(ESI,m / z):Calculated for C 26 H 21 NO 4 + [M+Na] + :464.1386,found:464.1382.

[0186]

[0187] HPLC analysis: 95:5 e.r. (Chiralcel IC 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 8.4 min, Rt (minor) = 6.0 min.

[0188] 9H-fluoren-9-yl (S)-N-benzyl-P-methylphosphonamidate (6r):

[0189]

[0190] 6r, white solid, m.p. 99.7–101.9 °C; 26.5 mg, 76% yield

[0191] 1 H NMR (400 MHz, CDCl 3 ) δ 6.63 (dd, J = 7.5, 1.2 Hz, 1H), 6.41–6.38 (m, 2H), 6.28 (dd, J = 7.5, 1.1 Hz, 1H), 6.17–6.12 (m, 2H), 6.10 (d, J = 2.3 Hz, 2H), 6.09–6.07 (m, 2H), 6.06–5.98 (m, 3H), 5.08 (d, J = 10.4 Hz, 1H), 3.19–2.93 (m, 2H), 1.91 (d, J = 8.3 Hz, 1H), 0.33 (d, J = 16.5 Hz, 3H).

[0192] 13 C NMR (101 MHz, CDCl 3 ) δ 142.7 (d, J = 4.0 Hz), 142.4 (d, J = 5.1 Hz), 140.6 (d, J = 47.5 Hz), 139.4 (d, J = 6.1 Hz), 129.5 (d, J = 6.1 Hz), 128.0 (d, J = 158.6 Hz), 127.9, 127.6 (d, J = 20.2 Hz), 126.2 (d, J = 83.8 Hz), 119.9 (d, J = 22.2 Hz), 75.4 (d, J = 7.1 Hz), 45.0, 14.0 (d, J = 132.3 Hz).

[0193] 31 P NMR (162 MHz, CDCl 3 ) δ 34.3.

[0194] HRMS (ESI, m / z): Calculated for C 21 H 20NNaO 2 P + [M+Na] + :372.1124, found: 372.1128.

[0195]

[0196] HPLC analysis: 93:7 e.r. (Chiralcel ODH 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 13.9 min, Rt (minor) = 24.9 min.

[0197] 9H-Fluoren-9-yl (S)-P-phenyl-N-propylphosphonamidate (7a):

[0198]

[0199] 7a, white solid m.p. 149.8–150.4 °C; 31.5 mg, 87% yield

[0200] 1 H NMR (400 MHz, CDCl 3 ) δ 7.89 (ddd, J = 13.0, 8.2, 1.4 Hz, 2H), 7.80 (dd, J = 7.5, 1.0 Hz, 1H), 7.64 (ddt, J = 11.4, 7.5, 1.0 Hz, 2H), 7.56–7.51 (m, 1H), 7.49 (t, J = 0.9 Hz, 1H), 7.48–7.45 (m, 1H), 7.44–7.40 (m, 2H), 7.34 (dtd, J = 8.6, 7.5, 1.2 Hz, 2H), 7.21 (td, J = 7.5, 1.1 Hz, 1H), 6.37 (d, J = 10.0 Hz, 1H), 3.03–2.91 (m, 3H), 1.56–1.47 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H).

[0201] 13 C NMR (101 MHz, CDCl 3)δ142.7(d,J = 4.0Hz), 142.3(d,J = 4.0Hz), 140.6(d,J = 30.3Hz), 132.0(d,J = 3.0Hz), 131.8(d,J = 10.1Hz), 129.4(d,J = 12.1Hz), 128.4(d,J = 15.2Hz), 127.8(d,J = 6.1Hz), 126.3(d,J = 34.3Hz), 119.9(d,J = 17.2Hz), 75.8(d,J = 5.1Hz), 42.8, 25.0(d,J = 6.1Hz), 11.2.

[0202] 31 P NMR(162MHz, CDCl 3 )δ24.6.

[0203] HRMS(ESI, m / z): Calculated for C 22 H 22 NNaO 2 P + [M + Na] + : 386.1280, found: 386.1277.

[0204]

[0205] HPLC analysis: 98:2 e.r. (Chiralcel ID 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt(major) = 11.1 min, Rt(minor) = 13.5 min.

[0206] 9H-Fluoren-9-yl (S)-N-isopropyl-P-phenylphosphonamidate(7b):

[0207]

[0208] 7b, white solid m.p. 171.2–173.4 °C; 29.4 mg, 81% yield

[0209] 1 H NMR(400MHz, CDCl 3)δ7.91(ddd,J=13.0,8.3,1.5Hz,2H),7.86–7.84(d,J=8.0Hz,1H),7.64(dd,J=11.6,7.5Hz,2H),7.56–7.51(m,1H),7.49–7.44(m,2H),7.43–7.39(m,2H),7.34(tt,J=7.5,1.4Hz,2H),7.19(td,J=7.5,1.1Hz,1H),6.34(d,J=10.0Hz,1H),3.61–3.47(m,1H),2.70(t,J=9.7Hz,1H),1.15(t,J=14.4Hz,6H).

[0210] 13 C NMR(101MHz,CDCl 3 )δ142.8(d,J=4.0Hz),142.6(d,J=4.0Hz),140.6(d,J=21.2Hz),132.7,131.9(d,J=18.7Hz),131.8(d,J=9.1Hz),129.4(d,J=12.1Hz),128.4(d,J=14.1Hz),127.8(d,J=3.0Hz),126.3(d,J=9.1Hz),119.9(d,J=13.1Hz),75.9(d,J=7.1Hz),43.4,25.7(dd,J=5.0,2.4Hz).

[0211] 31 P NMR(162MHz,CDCl 3 )δ22.6.

[0212] HRMS(ESI,m / z):Calculated for C 22 H 22 NNaO 2 P + [M+Na] + :386.1280,found:386.1275.

[0213]

[0214] HPLC analysis:97:3e.r.(Chiralcel ID 40:60i-PrOH / n-Hexane,Flow:1.0mL / min),Rt(major)=6.2min,Rt(minor)=6.9min.

[0215] 9H-Fluoren-9-yl (S)-N-cyclopropyl-P-phenylphosphonamidate (7c):

[0216]

[0217] 7c, white solid, m.p. 149.8–150.6 °C; 30.7 mg, 85% yield

[0218] 1 H NMR (400 MHz, CDCl 3 ) δ 7.92 (ddd, J = 13.1, 8.3, 1.4 Hz, 2H), 7.87 (dd, J = 7.5, 1.0 Hz, 1H), 7.63 (ddt, J = 9.6, 7.6, 1.0 Hz, 2H), 7.57–7.53 (m, 1H), 7.47 (tdd, J = 7.1, 4.0, 1.8 Hz, 2H), 7.43–7.37 (m, 2H), 7.33 (td, J = 7.4, 1.2 Hz, 2H), 7.18 (td, J = 7.5, 1.1 Hz, 1H), 6.35 (d, J = 9.8 Hz, 1H), 3.45 (d, J = 10.4 Hz, 1H), 2.41–2.35 (m, 1H), 0.56–0.46 (m, 4H).

[0219] 13 C NMR (101 MHz, CDCl 3 ) δ 142.6 (d, J = 4.0 Hz), 142.4 (d, J = 5.1 Hz), 140.6 (d, J = 14.1 Hz), 132.1 (d, J = 3.0 Hz), 131.9 (d, J = 10.1 Hz), 129.4 (d, J = 11.1 Hz), 128.4 (d, J = 14.1 Hz), 127.7 (d, J = 3.0 Hz), 126.3 (d, J = 16.2 Hz), 119.9 (d, J = 7.1 Hz), 76.1 (d, J = 5.1 Hz), 22.7 (d, J = 1.0 Hz), 7.2 (dd, J = 22.6, 5.2 Hz).

[0220] 31 P NMR (162 MHz, CDCl 3 ) δ 24.9.

[0221] HRMS (ESI, m / z): Calculated for C 22 H 20 NNaO 2 P + [M+Na]+ : 384.1124, found: 384.1118.

[0222]

[0223] HPLC analysis: 97:3 e.r. (Chiralcel IA 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 5.1 min, Rt (minor) = 6.1 min.

[0224] 9H-Fluoren-9-yl (S)-N-cyclobutyl-P-phenylphosphonamidate (7d):

[0225]

[0226] 7d, white solid m.p. 151.7–153.2 °C 30.0 mg, 80% yield

[0227] 1 H NMR (400 MHz, CDCl 3 ) δ 7.85 (ddd, J = 13.1, 8.3, 1.5 Hz, 2H), 7.77 (dd, J = 7.3, 1.1 Hz, 1H), 7.66–7.62 (m, 2H), 7.58–7.56 (m, 1H), 7.53–7.49 (m, 1H), 7.45–7.43 (m, 1H), 7.43–7.39 (m, 2H), 7.34 (dtd, J = 15.0, 7.6, 1.1 Hz, 2H), 7.23 (td, J = 7.5, 1.1 Hz, 1H), 6.36 (d, J = 9.9 Hz, 1H), 3.80–3.67 (m, 1H), 3.34 (t, J = 10.2 Hz, 1H), 2.31–2.23 (m, 1H),, 2.19–2.09 (m, 1H),, 1.92–1.76 (m, 2H), 1.63–1.55 (m, 1H), 1.51–1.42 (m, 1H).

[0228] 13 C NMR (101 MHz, CDCl 3)δ142.6(d, J = 4.0Hz), 140.6(d, J = 33.3Hz), 131.9(d, J = 3.0Hz), 131.7(d, J = 10.1Hz), 131.4(d, J = 172.7Hz), 129.4(d, J = 12.1Hz), 128.4(d, J = 15.1Hz), 127.8(d, J = 27.3Hz), 126.3(d, J = 32.3Hz), 119.9(d, J = 16.2Hz), 75.7(d, J = 5.1Hz), 46.7(d, J = 1.0Hz), 33.9(d, J = 4.0Hz), 34.0.

[0229] 31 P NMR(162MHz, CDCl 3 )δ22.5.

[0230] HRMS(ESI, m / z): Calculated for C 23 H 22 NNaO 2 P + [M + Na] + : 398.1280, found: 398.1279.

[0231]

[0232] HPLC analysis: 97:3 e.r. (Chiralcel IA 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt(major) = 5.3 min, Rt(minor) = 6.3 min.

[0233] 9H-Fluoren-9-yl (S)-N-cyclopentyl-P-phenylphosphonamidate(7e):

[0234]

[0235] 7e, white solid m.p. 152.1–153.9 °C; 32.3 mg, 83% yield

[0236] 1 H NMR(400MHz, CDCl 3)δ7.90(ddd,J=13.0,8.3,1.4Hz,2H),7.84(dd,J=7.6,1.1Hz,1H),7.67–7.61(m,2H),7.56–7.51(m,1H),7.48–7.43(m,3H),7.40(dd,J=7.5,1.2Hz,1H),7.35(tdd,J=7.4,5.1,1.2Hz,2H),7.20(td,J=7.5,1.1Hz,1H),6.36(d,J=9.9Hz,1H),3.71–3.60(m,1H),2.87(t,J=9.5Hz,1H),1.93–1.77(m,2H),1.69–1.60(m,2H),1.56–1.45(m,2H),1.44–1.32(m,2H).

[0237] 13 C NMR(101MHz,CDCl 3 )δ142.7(d,J=4.0Hz),142.6(d,J=4.0Hz),140.6(d,J=25.3Hz),132.0(d,J=172.7Hz),131.9(d,J=9.1Hz),129.4(d,J=13.1Hz),128.4(d,J=14.1Hz),127.8(d,J=4.0Hz),126.3(d,J=16.2Hz),120.0(d,J=14.1Hz),75.9(d,J=5.1Hz),53.0,35.2(d,J=2.0Hz),23.1(d,J=4.0Hz).

[0238] 31 P NMR(162MHz,CDCl 3 )δ23.5.

[0239] HRMS(ESI,m / z):Calculated for C 24 H 24 NNaO 2 P + [M+Na] + :412.1437,found:412.1437.

[0240]

[0241] HPLC analysis: 97:3 e.r. (Chiralcel ID 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 6.8 min, Rt (minor) = 7.8 min.

[0242] 9H-Fluoren-9-yl (S)-N,N-diethyl-P-phenylphosphonamidate (7f):

[0243]

[0244] 7f, white solid, m.p. 159.1–160.9 °C; 27.2 mg, 72% yield

[0245] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.81 (ddd, J = 12.9, 8.3, 1.4 Hz, 2H), 7.73 (dd, J = 7.5, 1.0 Hz, 1H), 7.71–7.68 (m, 1H), 7.67–7.63 (m, 2H), 7.51–7.47 (m, 1H), 7.45–7.42 (m, 2H), 7.41–7.38 (m, 1H), 7.34 (ddd, J = 15.0, 8.0, 1.2 Hz, 2H), 7.23 (dd, J = 7.5, 1.1 Hz, 1H), 6.35 (d, J = 9.5 Hz, 1H), 3.28–3.20 (m, 4H), 1.08 (t, J = 7.1 Hz, 6H).

[0246] 13 13C NMR (101 MHz, CDCl 3 ) δ 142.8 (d, J = 3.0 Hz), 142.7 (d, J = 4.0 Hz), 140.6 (d, J = 43.4 Hz), 131.6 (d, J = 10.1 Hz), 131.5 (d, J = 3.0 Hz), 129.4 (d, J = 13.1 Hz), 128.3 (d, J = 14.1 Hz), 127.8 (d, J = 25.3 Hz), 126.4 (d, J = 84.8 Hz), 119.9 (d, J = 25.3 Hz), 75.7 (d, J = 6.1 Hz), 38.9 (d, J = 5.1 Hz), 14.1 (d, J = 2.0 Hz).

[0247] 31 31P NMR (162 MHz, CDCl 3 ) δ 24.9.

[0248] HRMS(ESI, m / z): Calculated for C 23 H 24 NNaO 2 P + [M + Na] + : 400.1473, found: 400.1421.

[0249]

[0250] HPLC analysis: 96:4 e.r. (Chiralcel ODH 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt(major) = 5.0 min, Rt(minor) = 15.9 min.

[0251] 9H-Fluoren-9-yl (S)-N,N-diallyl-P-phenylphosphonamidate (7g):

[0252]

[0253] 7g, white solid m.p. 100.4–101.3 °C; 28.5 mg, 71% yield

[0254] 1 H NMR (400 MHz, CDCl 3 ) δ 7.82 (ddd, J = 13.0, 6.9, 1.5 Hz, 2H), 7.73 (d, J = 7.5 Hz, 1H), 7.70–7.64 (m, 3H), 7.44 (dd, J = 4.8, 2.9 Hz, 2H), 7.43–7.38 (m, 2H), 7.38–7.31 (m, 2H), 7.26–7.22 (m, 1H), 6.38 (d, J = 9.4 Hz, 1H), 5.70–5.60 (m, 2H), 5.17–5.12 (m, 4H), 3.83–3.69 (m, 4H).

[0255] 13 C NMR (101 MHz, CDCl 3)δ142.6(d,JC3.0Hz),142.5(d,JC5.1Hz),140.6(d,JC40.4Hz),134.2(d,JC3.0Hz),131.9(d,JC10.1Hz),129.4(d,JC14.1Hz). ),128.4(d,JS14.1Hz),127.8(d,JS19.2Hz),126.8,126.0,119.9(d,JS24.2Hz),118.4,75.9(d,JS6.1Hz),47.1(d,JS5.1Hz).

[0256] 31 P NMR (162MHz, CDCl 3 )δ24.7.

[0257] HRMS(ESI,m / z):Calcd 25 H 24 NNaO 2 P.S + [M+Na] + :424.1437,found:424.1432.

[0258]

[0259] HPLC analysis:98:2e.r.(Chiralcel ODH 40:60i-PrOH / n-Hexane,Flow:1.0mL / min),Rt(major)D4.8min,Rt(minor)11.0min.

[0260] 9H-Fluoren-9-yl(S)-azetidin-1-yl(phenyl)phosphinate(7h):

[0261]

[0262] 7h,dose range mp127.6–128.5°C28.2mg,79% dose

[0263] 1 H NMR (400MHz, CDCl 3)δ7.90–7.86(m,2H),7.85–7.83(m,1H),7.64(dd,J=13.5,7.5Hz,2H),7.58–7.52(m,1H),7.51–7.46(m,2H),7.45–7.39(m,2H),7.38–7.31(m,2H),7.19(td,J=7.5,1.1Hz,1H),6.36(d,J=9.6Hz,1H),3.98–3.83(m,4H),2.37–2.21(m,2H).

[0264] 13 C NMR(101MHz,CDCl 3 )δ142.7(d,J=4.0Hz),142.5(d,J=4.0Hz),140.1(d,J=28.3Hz),132.0(d,J=3.0Hz),131.9(d,J=10.1Hz),129.4(d,J=14.1Hz),128.5(d,J=14.1Hz),127.8(d,J=3.0Hz),126.2(d,J=37.4Hz),119.9(d,J=17.2Hz),76.0(d,J=6.1Hz),48.6(d,J=3.0Hz),18.1(d,J=17.2Hz),

[0265] 31 P NMR(162MHz,CDCl 3 )δ23.6

[0266] HRMS(ESI,m / z):Calculated for C 22 H 20 NNaO 2 P+[M+Na] + :384.1124,found:384.1116.

[0267]

[0268] HPLC analysis:98:2e.r.(Chiralcel IC 40:60i-PrOH / n-Hexane,Flow:1.0mL / min),Rt(major)=15.3min,Rt(minor)=8.1min.

[0269] 9H-Fluoren-9-yl(S)-phenyl(pyrrolidin-1-yl)phosphinate(7i):

[0270]

[0271] 7i, white solid, m.p. 131.9–132.1 °C; 28.9 mg, 77% yield

[0272] 1 H NMR (400 MHz, CDCl 3 ) δ 7.86–7.80 (m, 2H), 7.79 (dd, J = 8.0, 1.3 Hz, 1H), 7.67–7.62 (m, 2H), 7.58 (dd, J = 7.5, 1.0 Hz, 1H), 7.54–7.49 (m, 1H), 7.47–7.44 (m, 2H), 7.42–7.36 (m, 2H), 7.35–7.32 (m, 1H), 7.23 (td, J = 7.5, 1.1 Hz, 1H), 6.38 (d, J = 9.6 Hz, 1H), 3.34–3.20 (m, 4H), 1.86–1.80 (m, 4H).

[0273] 13 C NMR (101 MHz, CDCl 3 ) δ 142.7 (d, J = 4.0 Hz), 140.6 (d, J = 37.4 Hz), 131.7 (d, J = 4.0 Hz), 131.5, 131.6 (d, J = 10.1 Hz), 129.3 (d, J = 12.1 Hz), 128.4 (d, J = 14.1 Hz), 127.8 (d, J = 14.1 Hz), 126.3 (d, J = 46.5 Hz), 119.9 (d, J = 19.2 Hz), 75.9 (d, J = 6.1 Hz), 46.8 (d, J = 5.1 Hz), 26.3 (d, J = 8.1 Hz).

[0274] 31 P NMR (162 MHz, CDCl 3 ) δ 23.0.

[0275] HRMS (ESI, m / z): Calculated for C 23 H 22 NNaO 2 P + [M+Na] + : 398.1280, found: 398.1278.

[0276]

[0277] HPLC analysis: 98:2 e.r. (Chiralcel IC, 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 10.0 min, Rt (minor) = 7.4 min.

[0278] Methyl ((S)-((9H-fluoren-9-yl)oxy)(phenyl)phosphoryl)-L-alaninate (7j):

[0279]

[0280] 7j, white solid, m.p. 134.7–136.8 °C; 33.0 mg, 81% yield

[0281] 1 1H NMR (400 MHz, CDCl 3 ) δ 7.91–7.85 (m, 2H), 7.78 (dq, J = 7.4, 0.9 Hz, 1H), 7.65–7.62 (m, 2H), 7.56–7.51 (m, 1H), 7.50–7.46 (m, 2H), 7.46–7.40 (m, 2H), 7.38–7.32 (m, 2H), 7.22 (td, J = 7.5, 1.1 Hz, 1H), 6.35 (d, J = 10.3 Hz, 1H), 4.20–4.06 (m, 1H), 3.66 (s, 3H), 3.64 (s, 1H), 1.42 (d, J = 7.0 Hz, 3H).

[0282] 13 13C NMR (101 MHz, CDCl 3 ) δ 174.4 (d, J = 7.1 Hz), 142.4 (d, J = 5.1 Hz), 142.3 (d, J = 4.0 Hz), 140.6 (d, J = 25.3 Hz), 132.2 (d, J = 3.0 Hz), 131.8 (d, J = 10.1 Hz), 129.5 (d, J = 10.1 Hz), 128.5 (d, J = 14.1 Hz), 127.8 (d, J = 2.0 Hz), 126.2 (d, J = 31.3 Hz), 119.9 (d, J = 15.2 Hz), 76.1 (d, J = 6.1 Hz), 52.4, 49.5 (d, J = 3.0 Hz), 21.8 (d, J = 4.0 Hz).

[0283] 31 31P NMR (162 MHz, CDCl 3 ) δ 23.2.

[0284] HRMS(ESI, m / z): Calculated for C 23 H 22 NNaO 4 P + [M + Na] + : 430.1179, found: 430.1170.

[0285] > 20:1 d.r. (determined by 1 H NMR).

[0286] Ethyl ((S)-((9H-fluoren-9-yl)oxy)(phenyl)phosphoryl)-L-alaninate (7k):

[0287]

[0288] 7k, white solid m.p. 121.9–123.7 °C; 35.0 mg, 83% yield

[0289] 1 H NMR (400 MHz, CDCl 3 ) δ 7.94–7.79 (m, 3H), 7.64 (ddt, J = 10.5, 7.5, 1.0 Hz, 2H), 7.58–7.48 (m, 2H), 7.49–7.39 (m, 3H), 7.35 (tdd, J = 7.4, 4.1, 1.2 Hz, 2H), 7.21 (td, J = 7.5, 1.1 Hz, 1H), 6.38 (d, J = 10.1 Hz, 1H), 4.28–4.12 (m, 1H), 4.07 (qt, J = 7.3, 3.7 Hz, 2H), 3.60 (t, J = 10.2 Hz, 1H), 1.41 (d, J = 7.0 Hz, 3H), 1.16 (t, J = 7.1 Hz, 3H).

[0290] 13 C NMR (101 MHz, CDCl 3)δ174.0(d, J = 6.1Hz), 142.5(d, J = 4.0Hz), 142.4(d, J = 5.1Hz), 140.6(d, J = 26.3Hz), 132.1(d, J = 3.0Hz), 131.7(d, J = 10.1Hz), 129.4(d, J = 12.1Hz), 128.4(d, J = 14.1Hz), 127.8, 126.3(d, J = 25.3Hz), 119.9(d, J = 15.2Hz), 76.1(d, J = 6.1Hz), 61.4, 49.7(d, J = 1.0Hz), 21.5(d, J = 4.0Hz), 14.0.

[0291] 31 P NMR(162MHz, CDCl 3 )δ22.7.

[0292] HRMS(ESI, m / z): Calculated for C 24 H 24 NNaO 4 P + [M + Na] + : 444.1335, found: 444.1322.

[0293] >20:1 d.r. (determined by 1 H NMR).

[0294] Methyl((S)-((9H-fluoren-9-yl)oxy)(phenyl)phosphoryl)-L-leucinate(7l):

[0295]

[0296] 7l, white solid, m.p. 109.3–111.5 °C; 34.6 mg, 77% yield.

[0297] 1 H NMR(400MHz, CDCl 3)δ7.90–7.84(m,2H),7.79(dd,J=7.5,0.9Hz,1H),7.63(ddt,J=11.0,7.6,0.9Hz,2H),7.55–7.50(m,1H),7.49–7.45(m,2H),7.45–7.43(m,2H),7.42–7.39(m,2H),7.20(td,J=7.5,1.1Hz,1H),6.35(d,J=10.0Hz,1H),4.05–3.97(m,1H),3.58(s,3H),3.44(t,J=10.1Hz,1H),1.81–1.69(m,1H),1.62–1.48(m,2H),0.84(dd,J=13.2,6.6Hz,6H).

[0298] 13 C NMR(101MHz,CDCl 3 )δ174.5(d,J=4.0Hz),142.5(d,J=4.0Hz),142.3(d,J=4.0Hz),140.6(d,J=22.2Hz),132.1(d,J=3.0Hz),131.8(d,J=10.1Hz),130.0,129.5(d,J=11.1Hz),128.4(d,J=15.2Hz),127.8,126.3(d,J=32.3Hz),119.9(d,J=14.1Hz),76.2(d,J=6.1Hz),52.3(d,J=1.0Hz),52.2(d,J=1.0Hz),52.0,44.3(d,J=6.1Hz),24.4,22.3(d,J=69.7Hz).

[0299] 31 P NMR(162MHz,CDCl 3 )δ23.2.

[0300] HRMS(ESI,m / z):Calculated for C 26 H 28 NNaO 4 P + [M+Na] + :472..1648,found:472.1629.

[0301] >20:1d.r.(determined by 1 H NMR).

[0302] Ethyl ((S)-((9H-fluoren-9-yl)oxy)(phenyl)phosphoryl)-L-phenylalaninate (7m):

[0303]

[0304] 7m, white solid, m.p. 129.7–130.7 °C; 36.2 mg, 75% yield

[0305] 1 H NMR (400 MHz, CDCl 3 ) δ 7.82 (ddd, J = 13.3, 8.3, 1.4 Hz, 2H), 7.70–7.58 (m, 3H), 7.56–7.47 (m, 2H), 7.47–7.39 (m, 3H), 7.39–7.34 (m, 1H), 7.33–7.29 (m, 1H), 7.22 (dd, J = 7.5, 1.1 Hz, 1H), 7.20–7.14 (m, 3H), 7.10 (dd, J = 7.9, 1.7 Hz, 2H), 6.22 (d, J = 10.1 Hz, 1H), 4.57–4.29 (m, 1H), 3.59 (s, 3H), 3.47 (t, J = 10.3 Hz, 1H), 3.07 (d, J = 6.0 Hz, 2H).

[0306] 13 C NMR (101 MHz, CDCl 3 ) δ 173.1 (d, J = 6.1 Hz), 142.4 (d, J = 5.1 Hz), 142.5 (d, J = 4.0 Hz), 140.6 (d, J = 26.3 Hz), 135.8, 132.1 (d, J = 3.0 Hz), 131.7 (d, J = 4.0 Hz), 131.6, 129.9, 129.0 (d, J = 102.0 Hz), 128.9 (d, J = 103.0 Hz), 127.8 (d, J = 8.1 Hz), 127.0, 126.3 (d, J = 46.5 Hz), 119.9 (d, J = 16.2 Hz), 76.1 (d, J = 6.1 Hz), 54.7 (d, J = 2.0 Hz), 52.1, 40.9 (d, J = 4.0 Hz).

[0307] 31 P NMR (162 MHz, CDCl 3 ) δ 23.2.

[0308] HRMS (ESI, m / z): Calculated for C 29 H26 NNaO 4 P + [M+Na] + :506.1492,found:506.1472.

[0309] >20:1 d.r. (determined by 1 H NMR).

[0310] Ethyl ((S)-((9H-fluoren-9-yl)oxy)(phenyl)phosphoryl)-L-tryptophanate (7n):

[0311]

[0312] 7n, white solid, m.p. 127.7–129.2 °C; 39.1 mg, 73% yield

[0313] 1 H NMR (400 MHz, CDCl 3 ) δ 8.12 (s, 1H), 7.75–7.70 (m, 2H), 7.69–7.67 (m, 1H), 7.62 (t, J = 7.4 Hz, 2H), 7.54 (d, J = 7.5 Hz, 1H), 7.49–7.43 (m, 2H), 7.40–7.37 (m, 1H), 7.36–7.34 (m, 2H), 7.33–7.28 (m, 2H), 7.25 (td, J = 7.3, 1.1 Hz, 1H), 7.22–7.13 (m, 2H), 7.03 (ddd, J = 8.0, 7.1, 1.0 Hz, 1H), 6.97 (d, J = 2.4 Hz, 1H), 6.37 (d, J = 10.1 Hz, 1H), 4.53–4.45 (m, 1H), 3.99–3.88 (m, 2H), 3.52 (t, J = 10.8 Hz, 1H), 3.32–3.21 (m, 2H), 1.02 (t, J = 7.2 Hz, 3H).

[0314] 13 C NMR (101 MHz, CDCl 3)δ173.1(d, J = 4.0 Hz), 142.5(d, J = 5.1 Hz), 142.4(d, J = 3.0 Hz), 140.6(d, J = 21.2 Hz), 136.0, 132.0(d, J = 3.0 Hz), 131.5(d, J = 10.1 Hz), 129.4(d, J = 8.1 Hz), 128.3(d, J = 11.1 Hz), 127.8, 127.6, 126.3(d, J = 41.4 Hz), 126.3(d, J = 41.4 Hz), 122.6(d, J = 99.9 Hz), 119.9(d, J = 13.1 Hz), 119.5, 118.6, 111.1, 110.0, 76.1(d, J = 6.1 Hz), 61.3, 54.6, 30.6(d, J = 6.1 Hz), 13.9.

[0315] 31 P NMR(162 MHz, CDCl 3 )δ22.7.

[0316] HRMS(ESI, m / z): Calculated for C 32 H 29 N 2 NaO 4 P + [M + Na] + : 559.1757, found: 559.1738.

[0317] >20:1 d.r. (determined by 1 H NMR).

[0318] Methyl((S)-((9H-fluoren-9-yl)oxy)(phenyl)phosphoryl)-D-leucyl-D-leucinate(7o):

[0319]

[0320] 7o, white solid m.p. 143.7–148.3 °C; 44.4 mg, 79% yield

[0321] 1 H NMR(400 MHz, CDCl 3)δ7.92(ddd,J=13.2,8.3,1.4Hz,2H),7.86(dq,J=7.4,0.9Hz,1H),7.62(ddt,J=8.7,7.7,1.0Hz,2H),7.58–7.54(m,1H),7.50–7.45(m,2H),7.41(dd,J=7.5,1.2Hz,1H),7.39–7.36(m,1H),7.35–7.30(m,2H),7.18(td,J=7.5,1.1Hz,1H),6.88(d,J=7.7Hz,1H),6.24(d,J=10.1Hz,1H),4.50–4.44(m,1H),3.98–3.89(m,1H),3.65(s,3H),3.45(dt,J=13.4,10.3Hz,1H),1.74–1.59(m,3H),1.55–1.46(m,3H),0.85(d,J=6.3Hz,3H),0.78(d,J=6.2Hz,3H),0.72(d,J=6.1Hz,6H).

[0322] 13 C NMR(101MHz,CDCl 3 )δ173.2(d,J=2.0Hz),172.9,142.3(d,J=4.0Hz),142.1(d,J=5.1Hz),140.5(d,J=7.1Hz),132.4(d,J=3.0Hz),131.8(d,J=10.1Hz),130.60(d,J=174.7Hz),129.5(d,J=13.1Hz),128.5(d,J=14.1Hz),127.8(d,J=24.2Hz),126.2(d,J=9.1Hz),119.9(d,J=8.1Hz),76.3(d,J=5.1Hz),53.2,52.1,50.8,43.3(d,J=6.1Hz),41.1,24.5(d,J=30.3Hz),22.7(d,J=29.3Hz),21.7(d,J=15.2Hz).

[0323] 31 P NMR(162MHz,CDCl 3 )δ24.1.

[0324] HRMS(ESI,m / z):Calculated for C 30 H 33 N 3 O 3 P + [M+Na]+ : 585.2489, found: 585.2499.

[0325] > 20:1 d.r. (determined by 1 H NMR).

[0326] 9H-Fluoren-9-yl (S)-N-(((1S,4aR,10aR)-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthren-1-yl)methyl)-P-phenylphosphonamidate (7p):

[0327]

[0328] 7p, white solid m.p. 123.9–125.6 °C; 45.4 mg, 77% yield

[0329] 1 H NMR (400 MHz, CDCl 3 ) δ 7.92–7.85 (m, 2H), 7.84–7.83 (m, 1H), 7.64–7.59 (m, 2H), 7.54–7.50 (m, 1H), 7.46–7.42 (m, 2H), 7.41–7.36 (m, 1H), 7.35–7.32 (m, 2H), 7.27–7.22 (m, 1H), 7.17 (td, J = 7.5, 1.1 Hz, 1H), 7.13 (d, J = 8.2 Hz, 1H), 6.97 (dd, J = 8.2, 2.1 Hz, 1H), 6.84 (d, J = 2.0 Hz, 1H), 6.30 (d, J = 10.1 Hz, 1H), 2.93–2.85 (m, 2H), 2.84–2.79 (m, 2H), 2.78–2.73 (m, 2H), 2.70 (dd, J = 17.1, 8.5 Hz, 1H), 2.22–2.22 (m, 1H), 1.70–1.61 (m, 4H), 1.44 (dd, J = 10.1, 4.6 Hz, 1H), 1.35–1.31 (m, 3H), 1.22 (d, J = 6.9 Hz, 6H), 1.17 (s, 3H), 0.86 (s, 3H)

[0330] 13 C NMR (101 MHz, CDCl 3)δ 146.3 (d, J = 162.6 Hz), 142.6 (d, J = 4.0 Hz), 142.4 (d, J = 4.5 Hz), 140.5 (d, J = 13.1 Hz), 134.6, 132.1, 132.0 (d, J = 3.0 Hz), 132.9 (d, J = 10.1 Hz), 130.4, 129.4 (d, J = 9.1 Hz), 128.4 (d, J = 14.1 Hz), 127.8 (d, J = 9.1 Hz), 126.8, 126.2 (d, J = 11.1 Hz), 123.9 (d, J = 32.3 Hz), 119.9 (d, J = 9.1 Hz), 76.1 (d, J = 5.1 Hz), 51.9, 45.1, 38.3, 37.3, 37.2 (d, J = 6.1 Hz), 35.6, 33.4, 29.8, 25.1, 23.9 (d, J = 4.0 Hz), 18.7, 18.6, 18.4.

[0331] 31 P NMR (162 MHz, CDCl 3 ) δ 25.2.

[0332] HRMS (ESI, m / z): Calculated for C 39 H 44 NNaO 2 P + [M + Na] + : 612.3002, found: 612.2975.

[0333] > 20:1 d.r. (determined by 1 H NMR).

[0334] 9H - Fluoren - 9 - yl

[0335] (S) - N - (5 - butyl - 4 - methyl - 6 - oxo - 1,6 - dihydropyrimidin - 2 - yl) - N - ethyl - P - phenylphosphonamidate (7q):

[0336]

[0337] 7q, white solid, m.p. 136.5–137.8 °C; 41.1 mg, 80% yield

[0338] 1 H NMR (400 MHz, CDCl 3)δ7.96(ddd,J=14.3,6.9,1.4Hz,2H),7.79(d,J=7.6Hz,1H),7.74(d,J=7.5Hz,1H),7.65(dd,J=10.5,7.5Hz,2H),7.56–7.51(m,1H),7.47–7.40(m,3H),7.39–7.35(m,1H),7.31(td,J=7.5,1.1Hz,1H),7.29–7.24(m,1H),6.83(d,J=10.1Hz,1H),4.80(s,1H),3.17(p,J=6.9Hz,2H),2.51(dd,J=9.2,6.6Hz,2H),2.32(s,3H),1.52–1.45(m,2H),1.37–1.28(m,2H),1.02(t,J=7.2Hz,3H),0.86(t,J=7.3Hz,3H).

[0339] 13 C NMR(101MHz,CDCl 3 )δ168.6,163.4(d,J=7.1Hz),159.5,142.2(d,J=4.0Hz),142.1(d,J=6.1Hz),140.6(d,J=29.3Hz),132.5(d,J=3.0Hz),131.8(d,J=10.1Hz),129.6(d,J=10.1Hz),128.3(d,J=16.2Hz),127.9(d,J=21.2Hz),126.3(d,J=76.7Hz),119.9(d,J=18.2Hz),109.3(d,J=7.1Hz),77.4(d,J=7.1Hz),36.2,31.8,25.0,22.7,21.7,14.9,13.9.

[0340] 31 P NMR(162MHz,CDCl 3 )δ16.9.

[0341] HRMS(ESI,m / z):Calculated for C 30 H 33 N 3 O 3 P + [M+H] + :514.2254,found:514.2241.

[0342] >20:1d.r.(determined by 11H NMR).

[0343] HPLC analysis: 98:2 e.r. (Chiralcel IG 40:60 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 8.5 min, Rt (minor) = 12.2 min.

[0344] 3-Ethyl 5-methyl (R)-2-((2-(((S)-((9H-fluoren-9-yl)oxy)(phenyl)phosphoryl)amino)ethoxy)methyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate (7r):

[0345]

[0346] 7r, white solid, m.p. 185.7–187.6 °C; 52.7 mg, 74% yield.

[0347] 1 1H NMR (400 MHz, CDCl 3 ) δ 8.00 (s, 1H), 7.94–7.87 (m, 2H), 7.86 (dd, J = 7.4, 1.0 Hz, 1H), 7.64 (ddt, J = 11.1, 7.5, 1.0 Hz, 2H), 7.59–7.53 (m, 1H), 7.51–7.45 (m, 2H), 7.41 (td, J = 7.6, 1.2 Hz, 1H), 7.37–7.33 (m, 1H), 7.33–7.29 (m, 3H), 7.21–7.15 (m, 2H), 7.02–6.97 (m, 2H), 6.36 (d, J = 10.2 Hz, 1H), 5.39 (s, 1H), 4.69 (s, 2H), 4.10–3.97 (m, 2H), 3.60 (s, 3H), 3.59–7.54 (m, 1H), 3.41–3.34 (m, 2H), 3.27–3.16 (m, 1H), 2.36 (s, 3H), 1.18 (t, J = 7.1 Hz, 3H).

[0348] 13 13C NMR (101 MHz, CDCl 3)δ168.1,167.2,146.1,145.3(d,JS35.4Hz),142.5(d,JS3.0Hz),142.3(d,JS5.1Hz),140.6(d,JS22. 2Hz), 132.3(d,J3.0Hz),132.1,131.9(d,J610.1Hz),131.8,131.4,130.1,129.5(d,J11.1Hz),129 .0,128.6(d,JS15.2Hz),127.8(d,JS7.1Hz),127.0(d,JS16.2Hz),126.0(d,JS9.1Hz),120.0(d,JS12 .1Hz),103.6,101.5,76.2(d,JC5.1Hz),71.7(d,J3.0Hz),68.1,59.7,50.7,40.8,36.9,19.0,14.3.

[0349] 31 P NMR (162MHz, CDCl 3 )δ25.3.

[0350] HRMS(ESI,m / z):Calcd 39 H 38 ClN 2 NaO 7 P.S + [M+Na] + :735.1997,found:735.1966.

[0351] >20:1d.r.(determined by 1 H NMR).

[0352] 9H-Fluoren-9-yl(S)-((1R,5R)-8-oxo-1,5,6,8-tetrahydro-2H-1,5-methanopyrido[1,2-a][1,5]diazocin-3(4H)-yl)(phenyl)phosphinate(7s):

[0353]

[0354] 7s,preparation of mp171.8–172.6°C35.1mg,71% of the drug

[0355] 1 H NMR (400MHz, CDCl 3)δ7.75(dd,J=7.4,1.1Hz,1H),7.67–7.62(m,2H),7.51–7.45(m,2H),7.45–7.43(m,1H),7.43–7.40(m,2H),7.39–7.34(m,2H),7.33–7.28(m,2H),7.19(td,J=7.5,1.1Hz,1H),6.99(dd,J=9.0,6.8Hz,1H),6.36(dd,J=9.0,1.4Hz,1H),6.19(d,J=9.0Hz,1H),5.65(dd,J=6.9,1.3Hz,1H),4.04(d,J=15.7Hz,1H),3.94–3.84(m,2H),3.41–3.35(m,1H),3.07–3.00(m,2H),2.84(s,1H),2.43(d,J=5.9Hz,1H),1.96–1.86(m,2H).

[0356] 13 C NMR(101MHz,CDCl 3 )δ163.3,149.0,142.3(d,J=4.0Hz),142.2(d,J=4.0Hz),140.5(d,J=27.3Hz),138.5,131.9(d,J=3.0Hz),131.6(d,J=9.1Hz),129.5(d,J=17.2Hz),128.5(d,J=15.2Hz),127.8(d,J=9.1Hz),126.2(d,J=40.4Hz),119.9(d,J=19.2Hz),117.1,105.1,76.5(d,J=6.1Hz),50.9(d,J=1.0Hz),50.2(d,J=2.0Hz),49.0,34.2(d,J=6.1Hz),27.2(d,J=7.1Hz),25.9

[0357] 31 P NMR(162MHz,CDCl 3 )δ23.6.

[0358] HRMS(ESI,m / z):Calculated for C 30 H 27 N 2 NaO 3 P + [M+Na] + :517.1652,found:517.1633.

[0359] >20:1d.r.(determined by 1 H NMR).

[0360] Example 2

[0361] This embodiment provides a method for preparing derivatives 11a-11e of chiral phosphoramide compounds, comprising the following steps:

[0362]

[0363] Under nitrogen protection, R-MgBr (1.8 equiv.) and tetrahydrofuran (0.5 mL) were added to a 4.0 mL vial equipped with a magnetic stirrer, and the mixture was then cooled to -78 °C. 4d (0.1 mmol, 1.0 equiv.) was dissolved in 0.5 mL tetrahydrofuran, then slowly added dropwise to the reaction solution with a syringe and stirred overnight. After 9a was consumed (monitored by thin layer chromatography TLC), the reaction solution was quenched with saturated ammonium chloride solution and extracted with dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography on silica gel (dichloromethane / methanol = 100:1-50:1) gave pure products 11a-11e.

[0364] Shape and spectrum analysis of compound 11a:

[0365] Colorless oil; 10.2 mg, 73% yield

[0366] (R)-Methyl(phenyl)phosphine oxide(11a):

[0367]

[0368] 1 H NMR (400 MHz, CDCl 3 )δ8.25(q,J=3.8Hz,0.5H),7.76–7.69(m,2H),7.62–7.56(m,1H),7.55–7.50(m,2H),7.07(q,J=3.8Hz,0.5H),1.82(dd,J=13.9,3.8Hz,3H).

[0369] 13 C NMR (101 MHz, CDCl 3 )δ132.4(d,J=3.0Hz), 130.7(d,J=164.6Hz), 129.5(d,J=11.1Hz), 128.9(d,J=13.1Hz), 16.3(d,J=68.7Hz).

[0370] 31 P NMR (162 MHz, CDCl 3 )δ20.4.

[0371] HRMS(ESI,m / z):Calculated for C 7 H 10 OP + [M+H] + :141.0464,found:141.0462.

[0372]

[0373] HPLC analysis: 96: 4e.r. (Chiralcel ODH 20: 80i-PrOH / n-Hexane, Flow: 1.0mL / min), Rt (major) = 7.1min, Rt (minor) = 8.5min.

[0374] Shape and spectrum analysis of compound 11b:

[0375] Colorless oil; 10.9 mg, 71% yield

[0376] (R)-Ethyl(phenyl)phosphine oxide(11b):

[0377]

[0378] 1 H NMR (400 MHz, CDCl 3 )δ8.03(t,J=3.3Hz,0.5H),7.45–7.68(m,2H),7.61–7.56(m,1H),7.55–7.50(m ,2H),6.87(t,J=3.3Hz,0.5H),2.09–1.99(m,2H),1.18(dt,J=19.7,7.7Hz,3H).

[0379] 13 C NMR (101 MHz, CDCl 3 )δ132.4(d,J=3.0Hz), 130.6(d,J=96.0Hz), 129.9(d,J=11.1Hz), 128.9(d,J=13.1Hz), 23.2(d,J=68.7Hz), 5.4(d,J=4.0Hz).

[0380] 31 P NMR (162 MHz, CDCl 3)δ30.8.

[0381] HRMS(ESI,m / z):Calculated for C 8 H 12 OP + [M+H] + :155.0620,found:155.0616.

[0382]

[0383] HPLC analysis: 95:5e.r. (Chiralcel ODH 20:80i-PrOH / n-Hexane, Flow: 1.0mL / min), Rt(major)=6.4min, Rt(minor)=7.3min.

[0384] Shape and spectrum analysis of compound 11c:

[0385] Colorless oil; 15.1 mg, 70% yield

[0386] (R)-Benzyl(phenyl)phosphine oxide(11c):

[0387]

[0388] 1 H NMR (400 MHz, CDCl 3 )δ8.07(dd,J=4.1,2.9Hz,0.5H),7.57–7.53(m,1H),7.52–7.47(m,2H),7.46–7.44(m,1H),7.43–7.35(m,1H) ,7.29–7.26(m,1H),7.25–7.20(m,2H),7.08–7.04(m,2H),6.88(dd,J=4.1,2.9Hz,0.5H),3.53–3.31(m,2H).

[0389] 13 C NMR (101 MHz, CDCl 3 )δ132.6(d,J=2.9Hz),130.4(d,J=7.5Hz),130.1(d,J=10.6Hz),129.7(d,J=5.8Hz),128.8(d ,J=3.1Hz), 128.6(d,J=12.5Hz), 128.5(d,J=2.5Hz), 127.2(d,J=3.6Hz), 38.8(d,J=62.5Hz).

[0390] 31 P NMR (162 MHz, CDCl 3 )δ29.5.

[0391] HRMS(ESI,m / z):Calculated for C 13 H 13 NaOP + [M+Na] + :239.0596,found:239.0593.

[0392]

[0393] HPLC analysis: 97: 3e.r. (Chiralcel ODH 20: 80i-PrOH / n-Hexane, Flow: 1.0mL / min), Rt (major) = 9.0min, Rt (minor) = 10.4min.

[0394] Shape and spectrum analysis of compound 11d:

[0395] Colorless oil; 17.9 mg, 77% yield

[0396] (R)-(2-Methoxyphenyl)(phenyl)phosphine oxide(11d):

[0397]

[0398] 1 H NMR (400 MHz, CDCl 3 )δ8.80(s,0.5H),7.83–7.77(m,1H),7.76–7.71(m,2H),7.55(s,0.5H),7.54–7.50(m,2H),7.49– 7.43(m,2H)),7.11(tdd,J=7.4,1.9,0.8Hz,1H),6.92(ddd,J=8.4,5.6,0.9Hz,1H),3.78(s,3H).

[0399] 13 C NMR (101 MHz, CDCl 3)δ160.6(d,J=4.0Hz),134.4(d,J=2.0Hz),133.0(d,J=7.1Hz),132.1(d,J=105.0Hz),132.0(d,J=3.0Hz),130 .4(d,J=11.1Hz), 128.5(d,J=13.1Hz), 121.1(d,J=12.1Hz), 119.4(d,J=103.0Hz), 110.7(d,J=6.1Hz), 55.5.

[0400] 31 P NMR (162 MHz, CDCl 3 )δ14.3.

[0401] HRMS(ESI,m / z):Calculated for C 13 H 14 O 2 P + [M+H] + :233.0726,found:233.0726.

[0402]

[0403] HPLC analysis: 97: 3e.r. (Chiralcel ODH 20: 80i-PrOH / n-Hexane, Flow: 1.0mL / min), Rt (major) = 13.0min, Rt (minor) = 9.0min.

[0404] (R)-Mesityl(phenyl)phosphine oxide(11e):

[0405]

[0406] Shape and spectrum analysis of compound 11e:

[0407] Colorless oil; 16.6 mg, 68% yield

[0408] 1 H NMR (400 MHz, CDCl 3 )δ9.16(s,0.5H),7.96(s,0.5H),7.67–7.61(m,2H),7.55–7.50(m,1H),7.49–7.43(m,2H),6.91(d,J=3.9Hz,2H),2.46(s,6H),2.32(s,3H).

[0409] 13C NMR (101 MHz, CDCl 3 )δ142.8(d,J=2.0Hz),142.1(d,J=10.1Hz),132.3(d,J=99.0Hz),131.9(d,J=3.0Hz),130.5(d,J=1 1.1Hz), 130.3 (d, J = 11.1Hz), 128.8 (d, J = 12.1Hz), 124.3 (d, J = 104.0Hz), 21.4 (d, J = 9.1Hz), 21.3.

[0410] 31 P NMR (162 MHz, CDCl 3 )δ9.8.

[0411] HRMS(ESI,m / z):Calculated for C 15 H 18 OP + [M+H] + :245.1090,found:245.1088.

[0412]

[0413] HPLC analysis: 94:6e.r. (Chiralcel ODH 10:90i-PrOH / n-Hexane, Flow: 1.0mL / min), Rt(major)=14.0min, Rt(minor)=8.5min.

[0414] Example 3

[0415] This embodiment provides a method for preparing a chiral phosphoramide compound derivative 12a, comprising the following steps:

[0416]

[0417] Under nitrogen protection, NaH (60% w / w, 0.13mmol, 1.3equiv.) and tetrahydrofuran (0.5mL) were added to a 4.0mL vial equipped with a magnetic stirrer, and the mixture was stirred at -78°C for 15min, followed by a syringe dropwise addition of a tetrahydrofuran solution of 11d (0.5mL). The reaction was stirred at -78°C for 45min, and then a tetrahydrofuran solution of iodomethane (0.5mL) was added dropwise with a syringe. The reaction was stirred overnight, and after complete consumption of the raw material by TLC, the reaction solution was quenched with a saturated ammonium chloride solution and extracted with dichloromethane. The organic phases were combined and dried over anhydrous sodium sulfate, and the resulting mixture was concentrated under reduced pressure and purified by flash chromatography using (dichloromethane: methanol = 50: 1) to obtain a colorless oily compound (21.4mg, 81%, 96: 4e.r.).

[0418] Shape and spectrum analysis of compound 12a:

[0419] Colorless oil;

[0420] (S)-(2-Methoxyphenyl)(methyl)(phenyl)phosphine oxide(12a):

[0421]

[0422] 1 H NMR (400 MHz, CDCl 3 )δ7.97(ddd,J=13.1,7.6,1.8Hz,1H),7.77–7.72(m,2H),7.54–7.48(m,1H),7.47–7.39(m,3H),7. 10(tdd,J=7.4,1.8,0.9Hz,1H),6.89(dd,J=8.3,5.4Hz,1H),3.73(s,3H),2.08(d,J=14.0Hz,3H).

[0423] 13 C NMR (101 MHz, CDCl 3 )δ159.8(d,J=4.0Hz),134.9(d,J=105.0Hz),133.9(d,J=4.0Hz),133.8,131.2(d,J=3.0Hz),130.2(d,J=10.1Hz) ,128.1(d,J=12.1Hz),121.4(d,J=100.0Hz),120.9(d,J=11.1Hz),110.8(d,J=6.1Hz),55.2,16.1(d,J=74.7Hz).

[0424] 31 P NMR (162 MHz, CDCl 3 )δ28.5.

[0425] HRMS(ESI,m / z):Calculated for C 14 H 16 O 2 P + [M+H] + :247.0882,found:247.0881.

[0426]

[0427] HPLC analysis: 96: 4e.r. (Chiralcel IA 20: 80i-PrOH / n-Hexane, Flow: 1.0mL / min), Rt (major) = 9.3min, Rt (minor) = 8.3min.

[0428] Example 4

[0429] This embodiment provides a method for preparing a chiral phosphoramide compound derivative 12c, comprising the following steps:

[0430]

[0431] Under nitrogen protection, 11d (0.15 mmol, 3.0 equiv.), 2-vinylpyridine (0.05 mmol, 1.0 equiv.), diphenyl phosphate (0.15 mmol, 0.15 equiv.) and toluene (1.0 mL) were added to a 4.0 mL vial equipped with a magnetic stirrer. The reaction was stirred at room temperature for 48 h. The reaction was monitored by TLC, evaporated in vacuo, and concentrated. The mixture was purified by flash chromatography using (dichloromethane / methanol = 60: 1-20: 1) to obtain a colorless oil compound 12c (27.3 mg, 75%, 95: 5 e.r.).

[0432] Shape and spectrum analysis of compound 12c:

[0433] Colorless oil;

[0434] (S)-(2-Methoxyphenyl)(phenyl)(2-(pyridin-2-yl)ethyl)phosphine oxide(12c):

[0435]

[0436] 1 H NMR(400MHz,CDCl 3 )δ8.47(ddd,J=5.0,1.9,0.9Hz,1H),8.01(ddd,J=12.8,7.6,1.8Hz,1H),7.83–7.78(m,2H),7.50–7.44(m,2H),7.43–7.36(m,3H),7.09(dt,J=7.5,1.1Hz,2H),7.04(ddd,J=7.6,4.9,1.1Hz,1H),6.82(ddd,J=8.4,5.4,0.8Hz,1H),3.72(s,3H),3.19–3.00(m,2H),2.99–2.80(m,2H).

[0437] 13 C NMR(101MHz,CDCl 3 )δ160.8(d,J=14.1Hz),159.8(d,J=4.0Hz),149.1,136.3,134.4(d,J=5.1Hz),133.8(d,J=102.0Hz),132.8(d,J=2.0Hz),131.2(d,J=2.0Hz),130.7(d,J=10.1Hz),128.1(d,J=12.1Hz),123.1,121.2,121.0(d,J=11.1Hz),120.3(d,J=97.0Hz),110.7(d,J=7.1Hz),55.2,29.9(d,J=3.0Hz),28.6(d,J=73.7Hz).

[0438] 31 P NMR(162MHz,CDCl 3 )δ31.3.

[0439] HRMS(ESI,m / z):Calculated for C 19 H 17 NaO 3 P + [M+H] + :338.1304,found:338.1296.

[0440]

[0441] HPLC analysis: 95:5e.r. (Chiralcel IC 40: 60i-PrOH / n-Hexane, Flow: 1.0mL / min), Rt (major) = 30.9min, Rt (minor) = 20.6min.

[0442] Example 5

[0443] This embodiment provides a method for preparing a chiral phosphoramide compound derivative 13a, comprising the following steps:

[0444]

[0445] Under nitrogen protection, 12a (0.1 mmol, 1.0 equiv.), methyl trifluoromethanesulfonate (0.11 mmol, 1.1 equiv.) and ethylene glycol dimethyl ether (1.0 mL) were added to a 4.0 mL vial equipped with a magnetic stirrer. The mixture was stirred at room temperature for 2 h. Next, the reaction solution was cooled to -78 °C and lithium aluminum tetrahydride (0.25 mmol, 2.5 equiv.) was added all at once. After stirring for 5 h, the reaction mixture was treated with BH 3 -THF solution (0.15mmol, 1.5equiv.) was quenched, and the resulting mixture was extracted with ethyl acetate. The organic phase was concentrated and dried over anhydrous sodium sulfate. After vacuum concentration, the mixture was purified by flash chromatography using (petroleum ether: ethyl acetate = 20: 1) to obtain a white solid compound (27.3mg, 74%, 96: 4e.r.).

[0446] Shape and spectrum analysis of compound 13a:

[0447] White solid compound;

[0448]

[0449] 1 H NMR (400 MHz, CDCl 3 )δ7.87(ddd,J=13.8,7.6,1.8Hz,1H),7.62(ddt,J=11.3,6.4,1.7Hz,2H),7.49(dddd,J=8.4,7.4,1.8,1.0Hz,1H),7.45 –7.36(m,3H),7.06(tdd,J=7.5,2.1,1.0Hz,1H),6.88(ddd,J=8.4,3.4,1.0Hz,1H),3.69(s,3H),1.94(d,J=10.6Hz,3H).

[0450] 13C NMR (101 MHz, CDCl 3 )δ161.4,135.6(d,J=14.1Hz),133.7(d,J=2.0Hz),131.3(d,J=59.5Hz),131.2(d,J=9.1Hz),130.3(d,J=2.0Hz) ,128.3(d,J=10.1Hz),121.1(d,J=12.1Hz),117.4(d,J=54.5Hz),111.2(d,J=4.0Hz),55.3,10.5(d,J=42.4Hz).

[0451] 31 P NMR (162 MHz, CDCl 3 )δ31.3.

[0452] HRMS(ESI,m / z):Calculated for C 19 H 17 NaO 3 P + [M+Na] + :267.1081,found:267.1081.

[0453]

[0454] HPLC analysis: 96: 4e.r. (Chiralcel OJH 20: 80i-PrOH / n-Hexane, Flow: 1.0mL / min), Rt (major) = 15.7min, Rt (minor) = 9.7min.

[0455] Example 6

[0456] This example provides antibacterial activity tests of related compounds:

[0457] (1) Test method

[0458] ① The turbidity method was used to test the inhibitory activity of some target compounds against Xanthomonas oryzae pv.oryzae (Xoo) and Xanthomonas oryzae pv.oryzicola (Xoc), with thiophanate-methyl and chlorothiazol as positive controls. The specific operation steps are as follows:

[0459] The compound was dissolved in 150.0 μL dimethylformamide and diluted with 0.1% (V / V) Tween-20 to prepare a solution with a concentration of 25 μg / mL. 1.0 mL of the above solution was added to a non-toxic nutrient broth (NB: 1.5 g beef extract, 2.5 g peptone, 0.5 g yeast powder, 5.0 g glucose and 500 mL distilled water, pH = 7.0-7.2) liquid culture medium in a 4.0 mL test tube. Then, 40.0 μL of NB solution containing Xoo or Xoc was added to 5.0 mL of NB solution containing the test compound. The inoculated test tube was incubated at (28±1)°C by measuring the optical density (OD) at 595 nm. 595 ) to monitor culture growth and expressed as corrected turbidity. The relative inhibition rate was calculated as follows:

[0460] I(%)=(Ctur-Ttur) / Ctur×100%

[0461] Ctur: Corrected turbidity value for bacterial growth on untreated NB;

[0462] Ttur: turbidity value corrected for bacterial growth on treated NB;

[0463] I: relative inhibition rate;

[0464] Table 1. In vitro antibacterial activity of the target compounds against Xoo. [a]

[0465]

[0466] In Table 1: [a] average of three tests; [b] the inhibitory activity of the commercial drug chlorpyrifos was used as a positive control; [c] the inhibitory activity of the commercial drug thiophanate-methyl was used as a positive control.

[0467] Table 2. In vitro antibacterial activity of the target compounds against Xoc. [a]

[0468]

[0469]

[0470] In Table 2: [a] average of three tests; [b] the inhibitory activity of the commercial drug chlorpyrifos was used as a positive control; [c] the inhibitory activity of the commercial drug thiophanate-methyl was used as a positive control.

[0471] The inhibitory activity of the target compounds against Xanthomonas oryzae (Xoo) was tested by turbidity method with commercial agents thiophanate-methyl and chlorothiazol as positive controls at test concentrations of 100 and 50 μg / mL (see Table 1). The bioassay results showed that most products were very effective in inhibiting Xoo. It is worth noting that at a relatively low concentration of 50 μg / mL, 6d and 7q showed significant inhibitory effects. The chiral phosphamide compounds 6e and 6f with para-fluorine or bromine atoms showed an inhibition rate of more than 90% against Xoo, which was significantly better than the commercial bacterial fungicide chlorothiazol (BT).

[0472] At the same time, the inhibitory effect of this class of compounds on Xoc is also very promising (see Table 2). It is gratifying that at a concentration of 50 μg / mL, the inhibition rate of most tested compounds is comparable to or slightly higher than that of commercial drugs. Structure-activity relationship (SAR) analysis shows that the corresponding products when the 4-position electron-withdrawing chiral phosphamide is used as a substrate are more conducive to improving the biological activity of the compounds against bacteria.

[0473] Table 3. Study on the antibacterial effects of different configurations of compounds 6d, 6f, 7q [a]

[0474]

[0475] In Table 3: [a] average of three tests; [b] the inhibitory activity of the commercial drug chlorpyrifos was used as a positive control; [c] the inhibitory activity of the commercial drug thiophanate-methyl was used as a positive control.

[0476] We studied the effects of different configurations of compounds 6d, 6f, and 7q on the antibacterial activity of Xoo at different concentrations (see Table 3). It is noteworthy that (S)-6d and (S)-6f have significantly better inhibitory effects on Xoo than their racemates (±)-6d and (±)-6f. At the same time, compounds (S)-7q and (±)-7q have comparable inhibitory efficiencies on Xoo.

[0477] In addition, we also studied the effects of different configurations of compounds 6d, 6f, and 7q on the antibacterial activity of Xoc at different concentrations (see Table 3). Compounds (S)-6d, (S)-6f, and their racemates showed moderate inhibitory activity against Xoc. It is worth noting that (S)-7q showed a significantly high inhibition rate against Xoc (79.83% at 50 μg / mL, which was superior to its racemate (±)-7q.

[0478] Finally, it should be noted that the terms "comprises," "includes," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that includes a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements that are inherent to such process, method, article, or apparatus.

[0479] Although the preferred embodiments of the present invention have been described, those skilled in the art may make other changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0480] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A chiral phosphamide compound, characterized in that: The general structural formula of the chiral phosphamide compound is shown in Formula 1: In formula 1, the * phosphorus atom is a chiral phosphorus atom; R 1 Including any one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-methylphenyl, 4-phenylphenyl, 4-methoxyphenyl, 4-acetylphenyl, 3-chlorophenyl, 3-methoxyphenyl, 2-bromophenyl, 2-methoxyphenyl and methyl; In formula 1, the sphere It includes any one of n-propyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, allyl, phenyl, azetidinyl and tetrahydropyrrole.

2. The method for preparing a chiral phosphamide compound according to claim 1, characterized in that: The preparation method comprises: Mixing compound 1, benzoyl chloride, potassium carbonate, chiral catalyst C7 and toluene to obtain a mixture; The mixture is reacted at a certain temperature for a period of time to obtain a reaction solution; Adding 9-fluorenol to the reaction solution, stirring and reacting for a period of time to obtain a first mixed solution; The first mixed solution is subjected to column chromatography and concentrated, and the obtained concentrated product is dissolved in carbon tetrachloride to obtain a second mixed solution; Adding amine and triethylamine to the second mixed solution, reacting at a certain temperature for a period of time, to obtain a third mixed solution; Purifying the third mixed solution to obtain a chiral phosphamide compound; Wherein, the structural formula of the chiral catalyst C7 is shown in Formula 3: The structural formula of the compound 1 is as follows: R 1 The group includes any one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 4-cyanophenyl, 4-methylphenyl, 4-phenylphenyl, 4-methoxyphenyl, 4-acetylphenyl, 3-chlorophenyl, 3-methoxyphenyl, 2-bromophenyl, 2-methoxyphenyl and methyl.

3. The method for preparing a chiral phosphamide compound according to claim 2, characterized in that: The step of mixing compound 1, benzoyl chloride, potassium carbonate, chiral catalyst C7 and toluene to obtain a mixture specifically comprises: Under an inert atmosphere, compound 1, benzoyl chloride, potassium carbonate, chiral catalyst C7 and toluene are mixed to obtain a mixture; Wherein, the molar ratio of the compound 1, the benzoyl chloride and the potassium carbonate is 1:2:2; The molar ratio of the chiral catalyst C7 to the compound 1 is 15:

100.

4. The method for preparing a chiral phosphamide compound according to claim 2, characterized in that: The mixture is reacted at a certain temperature for a period of time to obtain a reaction solution, which specifically comprises: The mixture was stirred at -10°C for 15 min to obtain a reaction solution.

5. The method for preparing a chiral phosphamide compound according to claim 2, characterized in that: The step of adding 9-fluorenol to the reaction solution and stirring the reaction solution for a period of time to obtain a first mixed solution specifically comprises: Add 9-fluorenol to the reaction solution, and stir the mixture at -10°C for 72 hours to obtain a first mixed solution; The molar ratio of the 9-fluorenol to the compound 1 is 1.2:

1.

6. The method for preparing a chiral phosphamide compound according to claim 2, characterized in that: The first mixed solution is subjected to column chromatography and concentrated, and the concentrated product is dissolved in carbon tetrachloride to obtain a second mixed solution, which specifically includes: Using dichloromethane to perform column chromatography on the first mixed solution, and then concentrating under reduced pressure; The obtained concentrated product is dissolved in carbon tetrachloride to obtain a second mixed solution.

7. The method for preparing a chiral phosphamide compound according to claim 2, characterized in that: The step of adding amine and triethylamine to the second mixed solution and reacting them at a certain temperature for a period of time to obtain a third mixed solution specifically comprises: Adding amine and triethylamine to the second mixed solution, reacting at -20°C for 72 hours, to obtain a third mixed solution; The molar ratio of the amine, the triethylamine and the compound 1 is 2:2:

1.

8. The method for preparing a chiral phosphamide compound according to claim 2, characterized in that: Purifying the third mixed solution to obtain a chiral phosphamide compound specifically includes: The third mixed solution is purified by silica gel column chromatography to obtain a chiral phosphamide compound.

9. Use of a chiral phosphamide compound as claimed in claim 1 as or in the preparation of an agricultural antibacterial agent.

10. Use of a chiral phosphonamide compound according to claim 1 as or in the preparation of an antibacterial agent for bacterial blight of rice and / or rice leaf streak disease.

11. An agricultural antibacterial agent, characterized in that: The active ingredient of the agricultural antibacterial agent includes the chiral phosphamide compound described in claim 1.

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