A chiral nitrogen oxide compound and its preparation method and application

Abstract

The present invention discloses a chiral nitrogen oxide compound, its preparation method, and application, belonging to the fields of organic synthesis technology and pesticide antibacterial activity research technology. The present invention discloses a method for preparing chiral nitrogen oxide compounds from nitrogen oxides and bromocinnamaldehyde, and synthesizes a series of compounds. The derivatives have good universality, excellent yields (up to 86%), enantioselectivity (up to 96%), and good biological activity, which is of great research significance for the further development and utilization of chiral nitrogen oxide compounds.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis technology and pesticide antibacterial activity research, and specifically relates to a chiral nitrogen oxide compound and a preparation method and application thereof. Background Art

[0002] Optically active chiral sulfoxides, phosphine oxides, and amine oxides have found widespread application in biomedicine. Furthermore, these molecules are used as chiral ligands and organocatalysts in metal-catalyzed reactions. While chiral sulfoxides and phosphine oxides have advanced significantly, chiral amine oxides have remained relatively stagnant. The synthesis of chiral nitrogen compounds presents significant challenges, particularly due to the free flipping of lone pairs of electrons on nitrogen atoms and their rapid racemization at room temperature. Literature research indicates that enantioselective synthetic strategies for chiral nitrogen compounds typically utilize rigid backbone methods, amine N-oxides, N-centered metal coordination, and N-centered quaternary ammonium salts (ACS Cent. Sci. 2023, 9, 64–71; Nature 2021, 597, 70–76; Angew. Chem. Int. Ed. 2016, 55, 13043). Despite this, the asymmetric synthesis of nitrogen oxides controlled by organocatalysis remains a considerable challenge. In 2007, Ichiro Suzuki synthesized chiral nitrogen oxides using an enzymatic hydrolysis method, but this method had a very low enantioselective efficiency (Tetrahedron Lett. 2007, 48, 6873–6876). Summary of the Invention

[0003] The purpose of the present invention is to provide a chiral nitrogen oxide compound, a preparation method thereof and application in the antibacterial field, provide a class of chiral nitrogen oxide compounds with higher enantioselectivity, and find that they have good catalytic and sterilization properties, which has important research significance for the further development and utilization of chiral nitrogen oxide compounds.

[0004] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0005] A chiral nitrogen oxide compound, wherein the chiral nitrogen oxide compound has a general structural formula as shown in Formula 1:

[0006]

[0007] In formula 1, the nitrogen atom with * is a chiral nitrogen atom;

[0008] R 1It is one of benzyl, 4-methylphenyl, 4-isopropylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-nitrophenyl, 3-fluorophenyl, 3-chlorophenyl, 2-methoxyphenyl, 2-fluorophenyl, 2-bromophenyl, 2-bromo-5-fluorophenyl, 2,6-difluorophenyl, 2,6-dichlorophenyl, 2-fluoro-6-chlorophenyl, 1-naphthyl, 2-thienyl, phenyl, ethylphenyl, 4-chloroethylphenyl, cyclohexylmethyl, and butyl;

[0009] R 2 It is one of phenyl, 2-fluorophenyl, 2-bromophenyl, 4-fluorophenyl, 4-bromophenyl and 4-methoxyphenyl.

[0010] The preparation method of the chiral nitrogen oxide compound is as shown in Formula 2:

[0011]

[0012] In formula 2, the structural formula of NHC F is shown in formula 3:

[0013]

[0014] The structural formula of C-3 is shown in Formula 4:

[0015]

[0016] Preferably, the preparation reaction formula of Compound I is shown in Formula 5:

[0017]

[0018] Preferably, the preparation reaction formula of compound I is shown in Formula 6:

[0019]

[0020] The chiral nitrogen oxide compound is used as an organic catalyst in carbonyl addition reaction.

[0021] The chiral nitrogen oxide compound is used as an antibacterial agent for rice bacterial blight pathogen and citrus canker pathogen.

[0022] The derivative prepared using the chiral nitrogen oxide compound as a substrate has a general structural formula as shown in Formula 7:

[0023]

[0024] R 3 It is one of a benzene ring, a pyridine ring and their derivatives.

[0025] The derivative is used as an antibacterial agent for citrus canker bacteria.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The present invention discloses a method for preparing chiral nitrogen oxide compounds using nitrogen oxide and bromocinnamaldehyde, and synthesizes a series of compounds. The derivatives thereof have good universality, excellent yield (up to 86%), enantioselectivity (up to 96%) and good biological activity, which has important research significance for the further development and utilization of chiral nitrogen oxide compounds. DETAILED DESCRIPTION

[0028] The present invention will be further described below in conjunction with various embodiments. The embodiments of the present invention include but are not limited to the following embodiments.

[0029] Example 1

[0030] This embodiment provides a method for preparing the nitrogen oxide raw material described in the above technical solution. The synthesis route and method are as follows:

[0031]

[0032] Diethanolamine (0.5 g, 4.8 mmol) and anhydrous potassium carbonate (0.8 g, 5.7 mmol) were dissolved in anhydrous acetone (10.0 mL), and S1 (0.9 g, 5.2 mmol) was added dropwise to the reaction solution. The resulting reaction mixture was refluxed for 16 hours under good stirring. After the reaction was complete, the reaction mixture was diluted with cold water and extracted with CH2Cl2 / MeOH=10:1 (3 × 50 mL). Salt water (10.0 mL) was washed, and Na2SO4 was dried and concentrated to obtain S2, which was used directly in the next step without further purification.

[0033] Under nitrogen, 80% m-CPBA (0.9 g, 5.2 mmol) was added to a solution of diol S2 (1.0 g, 4.3 mmol) in CHCl (10.0 mL) and allowed to react at room temperature for 12 hours. After complete consumption of the starting material, the mixture was filtered and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (CHCl / MeOH = 3:1) to obtain the title compounds 1a-1y.

[0034]

[0035] Benzylamine (0.39 g, 3.6 mmol) and Et3N (0.73 g, 7.2 mmol) were dissolved in THF solution, and 3-bromo-1-propanol (1.0 g, 7.2 mmol) was slowly added dropwise to the reaction solution. The resulting reaction mixture was refluxed for 24 hours under good stirring. After completion of the reaction by thin layer chromatography (TLC), the reaction mixture was diluted with cold water and extracted with CH2Cl2 / MeOH=10:1 (3 × 50 mL). The combined organic layer was dried over Na2SO4 and concentrated to give a crude product. The residue was purified by silica gel column chromatography (CH2Cl2 / MeOH=15:1) to obtain S3.

[0036] Under nitrogen, 80% m-CPBA (0.9 g, 5.2 mmol) was added to a solution of S3 (1.0 g, 4.3 mmol) in CH2Cl2 (10.0 mL) and reacted at room temperature for 12 hours. Purification by silica gel column chromatography gave the title starting material 1z (CH2Cl2 / MeOH=3:1).

[0037] The present invention also provides a method for preparing the chiral nitrogen oxide compound using the above technical solution. The synthesis route and method are as follows:

[0038]

[0039] Under nitrogen, chiral NHC F (0.02 mmol, 20 mmol%), C-3 (0.02 mmol, 20 mmol%), substrate 1 (0.1 mmol, 1.0 equiv.), substrate 2 (0.12 mmol, 1.2 equiv.), and RbCO (0.15 mmol, 1.5 equiv.) were added to a 4.0 mL oven-dried vial equipped with a magnetic stir bar. Subsequently, CHCl / PhCl = 1:2 (10.0 mL) was added via syringe. The reaction mixture was then stirred at room temperature under nitrogen for 12 hours. Once the starting material was completely consumed, the resulting residue was purified by silica gel column chromatography (EtOAc to CHCl / MeOH = 20:1) to afford product 3.

[0040] The specific spectra of products 3a-3z are analyzed as follows:

[0041] (S,E)-N-benzyl-2-(cinnamoyloxy)-N-(2-hydroxyethyl)ethan-1-amine oxide(3a):

[0042]

[0043] 3a, colorless oil; 29 mg, 85% yield

[0044] 1 1H NMR (400 MHz, Chloroform-d) δ 7.7 (d, J = 16.0 Hz, 1H), 7.6–7.5 (m, 4H), 7.5–7.4 (m, 3H), 7.4 (dd, J = 5.1, 1.9 Hz, 3H), 6.4 (d, J = 16.0 Hz, 1H), 4.9 (t, J = 5.2 Hz, 2H), 4.7–4.5 (m, 2H), 4.2 (ddd, J = 13.2, 7.1, 2.7 Hz, 1H), 4.1 (ddd, J = 13.2, 5.9, 2.8 Hz, 1H), 3.7–3.3 (m, 4H).

[0045] 13 13C NMR (101 MHz, Chloroform-d) δ 166.5, 146.3, 134.0, 132.4, 130.8, 130.0, 129.7, 129.1, 129.0, 128.3, 116.8, 72.7, 64.2, 64.0, 58.2 (d, J = 2.4 Hz).

[0046] HRMS (ESI, m / z): Calculated for C 20 H 24 NO4 + [M + H] + : 342.1700, found: 378.1703.

[0047] [α] 2 D 5 = +2.461 (c = 1.0 in CHCl3).

[0048] HPLC analysis: 94:6 e.r. (Chiralcel ODH 75:25 i-PrOH / n-Hexane, Flow: 1.0 mL / min), Rt (major) = 32.9 min, Rt (minor) = 27.5 min.

[0049] (S,E)-N-Benzyl-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide (3b):

[0050]

[0051] 3b, colorless oil; 31.0 mg, 85% yield

[0052] 1 H NMR(400MHz,CD3OD)δ7.72(d,J=16.0Hz,1H),7.69–7.60(m,4H),7.50–7.25(m,3H),7.14(t,J=8.7Hz,2H),6.52(d,J=16.0Hz,1H),4.73(dt,J=5.9,4.4Hz,2H),4.57(s,2H),4.16–3.98(m,2H),3.74(ddd,J=13.9,6.4,4.4Hz,1H),3.59(ddd,J=13.9,5.8,4.3Hz,1H),3.47(ddd,J=13.6,6.6,4.0Hz,1H),3.39(ddd,J=13.5,5.9,4.0Hz,1H).

[0053] 13 C NMR(101MHz,CD3OD)δ166.4,164.1(d,J=250.4Hz),144.4,132.8,130.7(d,J=3.5Hz),130.2(d,J=8.4Hz),129.8,129.4,128.2,116.7(d,J=2.6Hz),115.6(d,J=22.4Hz),71.6,66.6,64.0,58.1,55.9ppm.

[0054] 19 FNMR(377MHz,CD3OD)δ-111.6ppm.

[0055] HRMS(ESI,m / z):Calculated for C 20 H 23 FNO4 + [M+H] + :360.1606,found:360.1604.

[0056] [α] 2 D 5 =+3.768(c=1.0in CHCl3).

[0057] HPLC analysis:95:5e.r.(Chiralcel ODH,17:83i-PrOH / n-Hexane,0.3mL / min),Rt(major)=69.6min,Rt(minor)=65.1min.

[0058] (S,E)-2-((3-(4-Fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)-N-(4-methylbenzyl)ethan-1-amine oxide (3c):

[0059]

[0060] 3c, colorless oil; 32 mg, 86% yield

[0061] 1 H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 16.0 Hz, 1H), 7.51 (dd, J = 8.6, 5.5 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 7.8 Hz, 2H), 7.08 (t, J = 8.6 Hz, 2H), 6.35 (d, J = 16.0 Hz, 1H), 4.86 (t, J = 5.2 Hz, 2H), 4.63–4.35 (m, 2H), 4.26 (ddd, J = 13.2, 7.0, 2.9 Hz, 1H), 4.06 (ddd, J = 13.2, 5.6, 2.9 Hz, 1H), 3.51 (ddd, J = 18.9, 13.7, 6.9 Hz, 2H), 3.44–3.29 (m, 2H), 2.37 (s, 3H).

[0062] 13 C NMR (101 MHz, CDCl3) δ 166.4, 164.1 (d, J = 252.2 Hz), 144.8, 140.2, 132.2, 130.3 (d, J = 3.3 Hz), 130.2 (d, J = 8.6 Hz), 129.8, 126.7, 116.7 (d, J = 2.2 Hz), 116.2 (d, J = 22.2 Hz), 72.6, 64.0, 63.9, 58.2, 58.1, 21.2 ppm.

[0063] 19 F NMR (376 MHz, CDCl3) δ -108.7 ppm.

[0064] HRMS (ESI, m / z): Calculated for C 21 H 25 FNO4 + [M + H] + : 374.1762, found: 374.1760.

[0065] [α] 2 D5 = +5.375 (c = 1.0 in CHCl3).

[0066] HPLC analysis: 91:9 e.r. (Chiralcel ID, 20:80 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 50.9 min, Rt (minor) = 41.7 min.

[0067] (S,E)-2-((3-(4-Fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)-N-(4-isopropylbenzyl)ethan-1-amine oxide (3d):

[0068]

[0069] 3d, colorless oil; 32 mg, 79% yield

[0070] 1 H NMR (400 MHz, Chloroform-d) δ 7.69 (d, J = 16.0 Hz, 1H), 7.51 (dd, J = 8.5, 5.4 Hz, 2H), 7.42 (d, J = 7.9 Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.08 (t, J = 8.5 Hz, 2H), 6.36 (d, J = 16.0 Hz, 1H), 4.88 (t, J = 5.2 Hz, 2H), 4.64–4.44 (m, 2H), 4.27 (ddd, J = 13.3, 6.5, 3.0 Hz, 1H), 4.06 (ddd, J = 13.3, 5.5, 3.0 Hz, 1H), 3.50–3.47 (m, 2H), 3.43–3.36 (m, 2H), 2.93–2.87 (m, 1H), 1.25 (d, J = 6.8 Hz, 6H).

[0071] 13 C NMR (101 MHz, Chloroform-d) δ 166.4, 164.1 (d, J = 252.1 Hz), 150.9, 144.8, 132.3, 130.3 (d, J = 3.8 Hz), 130.2 (d, J = 8.6 Hz), 127.2, 127.1, 116.7 (d, J = 2.6 Hz), 116.2 (d, J = 21.9 Hz), 72.6, 63.9 (d, J = 7.0 Hz), 58.2 (d, J = 6.5 Hz), 33.9, 23.8.

[0072] 19 FNMR (376 MHz, Chloroform-d) δ -108.7.

[0073] HRMS (ESI, m / z): Calculated for C 23 H 28 FNO4Na + [M + Na] + : 424.1895, found: 424.1897.

[0074] [α] 2 D 5 = +6.455 (c = 1.0 in CHCl3).

[0075] HPLC analysis: 91:9 e.r. (Chiralcel ID, 17:83 i-PrOH / n-Hexane, 0.3 mL / min), Rt (major) = 125.9 min, Rt (minor) = 147.8 min.

[0076] (S,E)-N-(4-Fluorobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide (3e):

[0077]

[0078] 3e, colorless oil; 21 mg, 57% yield

[0079] 1 H NMR (400 MHz, CD3OD) δ 7.74 (d, J = 16.1 Hz, 1H), 7.70 (d, J = 7.2 Hz, 2H), 7.66 (d, J = 7.6 Hz, 2H), 7.21 (t, J = 8.7 Hz, 2H), 7.15 (t, J = 9.1 Hz, 2H), 6.54 (d, J = 16.0 Hz, 1H), 4.77–4.62 (m, 4H), 4.22–3.99 (m, 2H), 3.96–3.88 (m, 1H), 3.73 (dt, J = 14.2, 4.9 Hz, 1H), 3.60 (ddd, J = 13.7, 6.7, 3.9 Hz, 1H), 3.49 (ddd, J = 13.7, 5.7, 3.8 Hz, 1H).

[0080] 1313C NMR (101 MHz, CDCl3) δ 166.4, 164.2 (d, J = 252.2 Hz), 163.7 (d, J = 250.7 Hz), 145.1, 134.5 (d, J = 8.4 Hz), 130.2 (d, J = 8.7 Hz), 125.4 (d, J = 3.6 Hz), 116.4, 116.3, 116.1 (d, J = 4.0 Hz), 115.9, 71.4, 64.5, 64.2, 58.2, 57.8 ppm.

[0081] 19 19F NMR (377 MHz, CDCl3) δ -108.5, -110.4 ppm.

[0082] HRMS (ESI, m / z): Calculated for C 20 H 22 F2NO4 + [M + H] + : 378.1511, found: 378.1516.

[0083] [α] 2 D 5 = +4.928 (c = 1.0 in CHCl3).

[0084] HPLC analysis: 96:4 e.r. (Chiralcel ODH, 15:85 i-PrOH / n-Hexane, 0.5 mL / min), Rt (major) = 51.7 min, Rt (minor) = 47.4 min.

[0085] (S,E)-N-(4-Chlorobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide (3f):

[0086]

[0087] 3f, colorless oil; 25 mg, 63% yield

[0088] 1H NMR(400MHz,CD3OD)δ7.73(d,J=16.0Hz,1H),7.69–7.62(m,4H),7.44(d,J=8.5Hz,2H),7.14(t,J=8.7Hz,2H),6.53(d,J=16.0Hz,1H),4.78–4.65(m,2H),4.64–4.34(m,2H),4.06(ddd,J=13.0,8.2,3.8Hz,2H),3.79(ddd,J=14.0,6.5,4.2Hz,1H),3.60(ddd,J=14.0,5.9,4.2Hz,1H),3.49(ddd,J=13.6,6.7,3.8Hz,1H),3.38(ddd,J=13.6,5.9,3.8Hz,1H).

[0089] 13 C NMR(101MHz,Methanol-d4)δ166.4,164.1(d,J=250.0Hz),144.4,135.6,134.4,131.1,130.7(d,J=3.2Hz),130.2(d,J=8.6Hz),128.5,128.3,116.7(d,J=2.6Hz),115.6(d,J=21.9Hz),70.5,66.7,64.2,58.0,55.9ppm.

[0090] 19 FNMR(377MHz,CD3OD)δ-111.57ppm.

[0091] HRMS(ESI,m / z):Calculated for C 20 H 22 ClFNO4 + [M+H] + :394.1216,found:394.1214.

[0092] [α] 2 D 5 =+5.168(c=1.0in CHCl3).

[0093] HPLC analysis:94:6e.r.(Chiralcel ODH,15:85i-PrOH / n-Hexane,0.5mL / min),Rt(major)=60.6min,Rt(minor)=53.4min.

[0094] (S,E)-N-(4-Bromobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-am ine oxide(3g):

[0095]

[0096] 3g, white solid, m.p. 143.8–145.7 °C; 35 mg, 81% yield

[0097] 1 H NMR (400 MHz, DMSO-d6) δ 7.82 (dd, J = 8.7, 5.7 Hz, 2H), 7.69 (d, J = 16.1 Hz, 1H), 7.61 (d, J = 8.6 Hz, 2H), 7.57 (d, J = 8.7 Hz, 2H), 7.27 (t, J = 8.9 Hz, 2H), 6.65 (d, J = 16.1 Hz, 1H), 4.65 (t, J = 5.2 Hz, 2H), 4.55–4.34 (m, 2H), 3.89 (t, J = 4.9 Hz, 2H), 3.57 (dt, J = 13.7, 5.1 Hz, 1H), 3.48–3.33 (m, 2H), 3.27–3.15 (m, 1H).

[0098] 13 C NMR (101 MHz, DMSO-d6) δ 166.4, 163.9 (d, J = 248.9 Hz), 144.3, 135.4, 131.4, 131.3, 131.1 (d, J = 3.2 Hz), 130.9, 123.2, 118.0, 116.4 (d, J = 21.8 Hz), 70.0, 64.9, 64.3, 58.9, 57.3 ppm.

[0099] 19 F NMR (376 MHz, DMSO-d6) δ -109.7 ppm.

[0100] HRMS (ESI, m / z): Calculated for C 20 H 22 BrFNO4 + [M+H] + : 438.0711, found: 438.0707.

[0101] [α] 2 D 5 = +7.367 (c = 1.0 in CHCl3).

[0102] HPLC analysis: 95:5 e.r. (Chiralcel ODH, 15:85 i-PrOH / n-Hexane, 0.5 mL / min), Rt (major) = 63.0 min, Rt (minor) = 56.7 min.

[0103] (S,E)-2-((3-(4-Fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)-N-(4-iodobenzyl)ethan-1-amine oxide (3h):

[0104]

[0105] 3h, colorless oil; 37 mg, 76% yield

[0106] 1 H NMR (400 MHz, CD3OD) δ 7.79 (d, J = 8.3 Hz, 2H), 7.71 (d, J = 16.1 Hz, 1H), 7.58 (dd, J = 8.7, 5.4 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 7.11 (t, J = 8.7 Hz, 2H), 6.42 (d, J = 16.0 Hz, 1H), 4.79–4.67 (m, 2H), 4.52–4.44 (m, 2H), 4.15–3.99 (m, 2H), 3.66 (ddd, J = 13.9, 6.0, 4.6 Hz, 1H), 3.56 (dt, J = 13.8, 4.8 Hz, 1H), 3.44 (ddd, J = 13.5, 6.6, 3.6 Hz, 1H), 3.40–3.30 (m, 1H).

[0107] 13 C NMR (101 MHz, CDCl3) δ 170.5, 168.1 (d, J = 251.9 Hz), 149.0, 141.8, 138.4, 134.2 (d, J = 8.6 Hz), 133.0, 120.3 (d, J = 2.2 Hz), 120.0, 119.8, 100.2, 75.3, 70.1, 68.2, 62.1, 60.3 ppm.

[0108] 19 F NMR (376 MHz, CDCl3) δ -105.6 ppm.

[0109] HRMS (ESI, m / z): Calculated for C 20 H22 FINO4 + [M+H] + :486.0572, found: 486.0574.

[0110] [α] 2 D 5 = +8.035 (c = 1.0 in CHCl3).

[0111] HPLC analysis: 93:7 e.r. (Chiralcel ID, 20:80 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 43.2 min, Rt (minor) = 38.4 min.

[0112] (S,E)-2-((3-(4-Fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)-N-(4-nitrobenzyl)ethan-1-amine oxide (3i):

[0113]

[0114] 3i, colorless oil; 27 mg, 68% yield

[0115] 1 H NMR (400 MHz, CDCl3) δ 8.28 (d, J = 8.7 Hz, 2H), 7.84 (d, J = 8.7 Hz, 2H), 7.70 (d, J = 16.0 Hz, 1H), 7.52 (dd, J = 8.8, 5.3 Hz, 2H), 7.10 (t, J = 8.6 Hz, 2H), 6.35 (d, J = 16.0 Hz, 1H), 4.79 (t, J = 5.1 Hz, 2H), 4.64 (d, J = 12.6 Hz, 1H), 4.52 (d, J = 12.6 Hz, 1H), 4.14 (t, J = 4.6 Hz, 2H), 3.71–3.50 (m, 3H), 3.40 (dt, J = 12.9, 4.5 Hz, 1H).

[0116] 1313C NMR (101 MHz, CDCl3) δ 166.3, 164.3 (d, J = 252.8 Hz), 148.8, 145.4, 136.3, 133.8, 130.2 (d, J = 8.7 Hz), 130.1 (d, J = 3.5 Hz), 123.7, 116.3 (d, J = 21.9 Hz), 116.2 (d, J = 2.4 Hz), 70.7, 65.31, 65.28, 58.2, 57.9 ppm.

[0117] 19 19F NMR (376 MHz, CDCl3) δ -108.3 ppm.

[0118] HRMS (ESI, m / z): Calculated for C 20 H 22 F N2O6 + [M + H] + : 405.1456, found: 405.1454.

[0119] [α] 2 D 5 = +3.727 (c = 1.0 in CHCl3).

[0120] HPLC analysis: 95:5 e.r. (Chiralcel ID, 50:50 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 13.3 min, Rt (minor) = 12.0 min.

[0121] (S,E)-N-(3-Fluorobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide (3j):

[0122]

[0123] 3j, colorless oil; 28 mg, 73% yield

[0124] 1H NMR(400MHz,CDCl3)δ7.62(d,J=15.9Hz,1H),7.44(dd,J=8.7,5.4Hz,2H),7.33(td,J=8.0,5.9Hz,1H),7.29–7.21(m,2H),7.08–7.01(m,1H),7.01(t,J=8.6Hz,2H),6.28(d,J=16.0Hz,1H),4.76(t,J=5.1Hz,2H),4.46(s,2H),4.07–4.01(m,2H),3.57–3.44(m,2H),3.36(ddd,J=13.0,6.5,2.7Hz,2H).

[0125] 13 C NMR(101MHz,CDCl3)δ166.3,164.2(d,J=253.5Hz),162.6(d,J=248.3Hz),145.1,131.8(d,J=7.8Hz),130.5(d,J=8.1Hz),130.2(d,J=8.1Hz),130.19(d,J=3.0Hz),128.2(d,J=3.0Hz),119.5(d,J=22.3Hz),117.1(d,J=21.0Hz),116.5(d,J=2.4Hz),116.2(d,J=21.9Hz),71.7,64.7,64.5,58.2,57.9ppm.

[0126] 19 FNMR(376MHz,CDCl3)δ-108.6,-111.3ppm.

[0127] HRMS(ESI,m / z):Calculated for C 20 H 22 F2NO4 + [M+H] + :378.1511,found:378.1507.

[0128] [α] 2 D 5 =+7.902(c=1.0in CHCl3).

[0129] HPLC analysis:94:6e.r.(Chiralcel ODH,15:85i-PrOH / n-Hexane,1.0mL / min),Rt(major)=24.5min,Rt(minor)=21.7min.

[0130] (S,E)-N-(3-Chlorobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-am ine oxide (3k):

[0131]

[0132] 3k, colorless oil; 16 mg, 40% yield

[0133] 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 16.1 Hz, 1H), 7.57 (s, 1H), 7.52 (dd, J = 8.7, 5.5 Hz, 2H), 7.45 (ddt, J = 11.5, 8.1, 1.5 Hz, 2H), 7.41–7.32 (m, 1H), 7.09 (t, J = 8.6 Hz, 2H), 6.36 (d, J = 16.0 Hz, 1H), 4.83 (dd, J = 6.0, 4.0 Hz, 2H), 4.57–4.42 (m, 2H), 4.27–4.04 (m, 2H), 3.58–3.51 (m, 2H), 3.44 (ddd, J = 13.0, 6.5, 2.6 Hz, 2H).

[0134] 13 C NMR (101 MHz, CDCl3) δ 166.3, 164.2 (d, J = 252.6 Hz), 145.1, 134.8, 132.5, 131.5, 130.7, 130.26, 130.22, 130.18, 116.5 (d, J = 2.7 Hz), 116.3, 116.1, 71.6, 64.7, 64.6, 58.2, 58.0 ppm.

[0135] 19 F NMR (376 MHz, CDCl3) δ -108.6 ppm.

[0136] HRMS (ESI, m / z): Calculated for C 20 H 22 ClFNO4 + [M + H] + : 394.1216, found: 394.1213.

[0137] [α] 2 D 5 = +3.601 (c = 1.0 in CHCl3).

[0138] HPLC analysis: 94:6 e.r. (Chiralcel ODH, 20:80 i-PrOH / n-Hexane, 0.5 mL / min), Rt (major) = 34.1 min, Rt (minor) = 31.4 min.

[0139] (S,E)-2-((3-(4-Fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)-N-(2-methoxybenzyl)ethan-1-amine oxide (3l):

[0140]

[0141] 3l, colorless oil; 26 mg, 68% yield

[0142] 1 H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 16.0 Hz, 1H), 7.56 (dd, J = 7.6, 1.8 Hz, 1H), 7.51 (dd, J = 8.8, 5.3 Hz, 2H), 7.42 (ddd, J = 8.3, 7.5, 1.7 Hz, 1H), 7.11–7.06 (m, 2H), 7.03 (td, J = 7.5, 1.1 Hz, 1H), 6.96 (dd, J = 8.4, 1.1 Hz, 1H), 6.34 (dd, J = 16.0, 0.6 Hz, 1H), 4.93–4.77 (m, 2H), 4.72 (d, J = 12.9 Hz, 1H), 4.52 (d, J = 12.9 Hz, 1H), 4.29 (ddd, J = 13.2, 7.5, 2.2 Hz, 1H), 4.02 (ddd, J = 13.2, 6.0, 2.5 Hz, 1H), 3.87 (s, 3H), 3.57 (ddd, J = 13.6, 6.2, 4.1 Hz, 1H), 3.52–3.43 (m, 2H), 3.39 (ddd, J = 13.0, 6.0, 2.2 Hz, 1H).

[0143] 1313C NMR (101 MHz, CDCl3) δ 166.4, 164.1 (d, J = 251.9 Hz), 158.3, 144.6, 134.9, 131.7, 130.3 (d, J = 3.4 Hz), 130.1 (d, J = 8.7 Hz), 121.1, 118.1, 116.8 (d, J = 2.6 Hz), 116.2 (d, J = 21.9 Hz), 111.1, 66.7, 64.4, 63.7, 58.5, 58.3, 55.5 ppm.

[0144] 19 19F NMR (376 MHz, CDCl3) δ -108.9 ppm.

[0145] HRMS (ESI, m / z): Calculated for C 21 H 25 FNO5 + [M + H] + : 390.1711, found: 390.1704.

[0146] [α] 2 D 5 = +5.570 (c = 1.0 in CHCl3).

[0147] HPLC analysis: 94:6 e.r. (Chiralcel ODH, 50:50 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 7.0 min, Rt (minor) = 5.5 min.

[0148] (S,E)-N-(2-Fluorobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide (3m):

[0149]

[0150] 3m, colorless oil; 28.6 mg, 76% yield

[0151] 1H NMR(400MHz,CDCl3)δ7.73(t,J=7.6,1.9Hz,1H),7.68(d,J=16.0Hz,1H),7.51(dd,J=8.7,5.5Hz,2H),7.49–7.37(m,1H),7.32–7.21(m,1H),7.14(t,J=9.8,8.3,1.2Hz,1H),7.08(t,J=8.6Hz,2H),6.35(d,J=16.0Hz,1H),4.93–4.72(m,2H),4.59(dd,2H),4.22(ddd,J=13.3,7.2,2.4Hz,1H),4.08(ddd,J=13.2,6.3,2.5Hz,1H),3.67–3.49(m,3H),3.39(ddd,J=13.0,6.4,2.3Hz,1H).

[0152] 13 C NMR(101MHz,CDCl3)δ166.3,164.2(d,J=252.5Hz),161.7(d,J=249.5Hz),144.8,135.2(d,J=2.9Hz),132.2(d,J=8.7Hz),130.3(d,J=3.7Hz),130.2(d,J=8.6Hz),124.8(d,J=3.6Hz),117.0(d,J=13.2Hz),116.7(d,J=2.3Hz),116.2(d,J=21.9Hz),115.8(d,J=22.5Hz),65.3,64.9,64.2,58.3,58.0ppm.

[0153] 19 FNMR(376MHz,CDCl3)δ-108.8,-114.9ppm.

[0154] HRMS(ESI,m / z):Calculated for C 20 H 22 F2NO4 + [M+H] + :378.1511,found:378.1513.

[0155] [α] 2 D 5 =+7.331(c=1.0in CHCl3).

[0156] HPLC analysis: 93:7 e.r. (Chiralcel ODH, 20:80 i-PrOH / n-Hexane, Flow: 0.5 mL / min), Rt (major) = 37.6 min, Rt (minor) = 34.8 min.

[0157] (S,E)-N-(2-Bromobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide (3n):

[0158]

[0159] 3n, colorless oil; 37 mg, 85% yield

[0160] 1 H NMR (400 MHz, CDCl3) δ 8.02 (dd, J = 7.8, 1.8 Hz, 1H), 7.69 (d, J = 16.0 Hz, 1H), 7.63 (dd, J = 8.0, 1.3 Hz, 1H), 7.59–7.47 (m, 2H), 7.41 (td, J = 7.5, 1.3 Hz, 1H), 7.30 (td, J = 7.7, 1.7 Hz, 1H), 7.09 (t, J = 8.6 Hz, 2H), 6.36 (d, J = 16.0 Hz, 1H), 4.97–4.73 (m, 2H), 4.63 (d, J = 12.7 Hz, 1H), 4.10 (t, J = 4.7 Hz, 2H), 3.77 (ddd, J = 13.9, 6.5, 3.5 Hz, 1H), 3.69–3.52 (m, 2H), 3.39 (dt, J = 13.0, 4.5 Hz, 1H).

[0161] 13 C NMR (101 MHz, CDCl3) δ 166.3, 164.2 (d, J = 252.2 Hz), 144.9, 136.0, 132.3 (d, J = 157.7 Hz), 130.3, 130.2 (d, J = 8.7 Hz), 129.3, 127.9, 126.9, 116.6 (d, J = 2.7 Hz), 116.2 (d, J = 21.9 Hz), 70.7, 65.7, 64.3, 58.4, 58.1 ppm.

[0162] 19 F NMR (376 MHz, CDCl3) δ -108.7 ppm.

[0163] HRMS(ESI, m / z): Calculated for C 20 H 22 BrFNO4 + [M + H] + : 438.0711, found: 438.0708.

[0164] [α] 2 D 5 = +8.269 (c = 1.0 in CHCl3).

[0165] HPLC analysis: 93:7 e.r. (Chiralcel ODH, 50:50 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 13.1 min, Rt (minor) = 8.3 min.

[0166] (S,E)-N-(2-Bromo-5-fluorobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide (3o):

[0167]

[0168] 3o, colorless oil; 38 mg, 86% yield

[0169] 1 1H NMR (400 MHz, CD3OD) δ 7.78 (dd, J = 9.6, 3.2 Hz, 1H), 7.74–7.68 (m, 2H), 7.68–7.62 (m, 2H), 7.25–7.04 (m, 3H), 6.52 (d, J = 16.0 Hz, 1H), 4.85–4.75 (m, 2H), 4.69 (ddd, J = 13.3, 6.1, 3.2 Hz, 2H), 4.06 (ddd, J = 13.1, 6.4, 3.3 Hz, 2H), 3.94 (ddd, J = 13.9, 7.0, 3.7 Hz, 1H), 3.63 (ddd, 13.9, 6.4, 3.5 Hz, 2H), 3.43 (ddd, J = 13.5, 5.9, 3.3 Hz, 1H).

[0170] 1313C NMR (101 MHz, Methanol-d4) δ 166.3, 164.1 (d, J = 250.3 Hz), 162.4 (d, J = 246.4 Hz), 144.4, 134.3 (d, J = 8.0 Hz), 131.7 (d, J = 8.1 Hz), 130.7 (d, J = 3.1 Hz), 130.2 (d, J = 8.6 Hz), 122.4 (d, J = 24.1 Hz), 121.2 (d, J = 3.0 Hz), 118.4 (d, J = 22.7 Hz), 116.7 (d, J = 2.3 Hz), 115.6 (d, J = 22.4 Hz), 70.0, 67.7, 64.7, 58.2, 55.9 ppm.

[0171] 19 19F NMR (377 MHz, Methanol-d4) δ -111.5, -115.7 ppm.

[0172] HRMS (ESI, m / z): Calculated for C 20 H 21 BrF2NO4 + [M+H] + : 456.0616, found: 456.0619.

[0173] [α] 2 D 5 = +4.601 (c = 1.0 in CHCl3).

[0174] HPLC analysis: 93:7 e.r. (Chiralcel ID, 30:70 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 17.3 min, Rt (minor) = 15.6 min.

[0175] (S,E)-N-(2,6-Difluorobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide (3p):

[0176]

[0177] 3p, colorless oil; 29 mg, 73% yield

[0178] 1H NMR(400MHz,CDCl3)δ7.67(d,J=16.0Hz,1H),7.54–7.48(m,2H),7.48–7.40(m,1H),7.08(t,J=8.6Hz,2H),7.03(t,J=8.4Hz,2H),6.34(d,J=16.0Hz,1H),4.97(ddd,J=13.1,6.5,3.9Hz,1H),4.89–4.69(m,2H),4.58(d,J=13.5Hz,1H),4.35(ddd,J=13.5,8.3,1.8Hz,1H),3.99(ddd,J=13.5,5.5,2.3Hz,1H),3.66–3.50(m,3H),3.34(dd,J=12.9,5.3Hz,1H).

[0179] 13 C NMR(126MHz,Acetone-d6)δ165.9,164.0(d,J=249.2Hz),162.8(dd,J=250.5,7.1Hz).143.8,132.5(t,J=10.8Hz),131.0(d,J=3.3Hz),130.6(d,J=8.6Hz),117.7(d,J=2.3Hz),115.9(d,J=22.0Hz),114.4–110.4(m),108.0(t,J=18.2Hz),64.9,64.2,59.4,58.6,57.9ppm. 19 FNMR(377MHz,CDCl3)δ-108.8,-108.9ppm.

[0180] HRMS(ESI,m / z):Calculated for C 20 H 21 F3NO4 + [M+H] + :396.1417,found:396.1427.

[0181] [α] 2 D 5 =+2.768(c=1.0in CHCl3).

[0182] HPLC analysis:97:3e.r.(Chiralcel ID,50:50i-PrOH / n-Hexane,1.0mL / min),Rt(major)=15.9min,Rt(minor)=19.6min.

[0183] (S,E)-N-(2-Chloro-6-fluorobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide (3q):

[0184]

[0185] 3q, colorless oil; 31 mg, 75% yield

[0186] 1 H NMR (400 MHz, CD3OD) δ 7.72 (d, J = 16.0 Hz, 1H), 7.66 (dd, J = 8.8, 5.4 Hz, 2H), 7.49 (td, J = 8.2, 6.0 Hz, 1H), 7.44–7.32 (m, 1H), 7.22 (ddd, J = 9.6, 8.3, 1.2 Hz, 1H), 7.14 (t, J = 8.7 Hz, 2H), 6.53 (d, J = 16.0 Hz, 1H), 4.82–4.64 (m, 2H), 4.16 (ddd, J = 13.1, 7.3, 3.2 Hz, 1H), 4.05 (ddd, J = 13.1, 5.8, 3.3 Hz, 1H), 3.97 (ddd, J = 13.9, 6.7, 3.9 Hz, 1H), 3.68 (ddd, J = 13.9, 6.6, 3.6 Hz, 2H), 3.53 (ddd, J = 13.5, 5.8, 3.2 Hz, 1H).

[0187] 13 C NMR (101 MHz, CD3OD) δ 166.4, 164.1 (d, J = 250.0 Hz), 163.1 (d, J = 251.9 Hz), 144.4, 138.3 (d, J = 4.6 Hz), 132.2 (d, J = 10.3 Hz), 130.7 (d, J = 3.0 Hz), 130.2 (d, J = 8.5 Hz), 126.0 (d, J = 3.5 Hz), 116.9 (d, J = 17.0 Hz), 116.7 (d, J = 2.5 Hz), 115.6 (d, J = 22.2 Hz), 114.5 (d, J = 23.4 Hz), 68.2, 65.0 (d, J = 2.2 Hz), 62.6, 58.2, 56.1 ppm.

[0188] 19 F NMR (377 MHz, CD3OD) δ -106.7, -111.5 ppm.

[0189] HRMS(ESI, m / z): Calculated for C 20 H 21 ClF2NO4 + [M + H] + : 412.1122, found: 412.1125.

[0190] [α] 2 D 5 = +8.522 (c = 1.0 in CHCl3).

[0191] HPLC analysis: 98:2 e.r. (Chiralcel ID, 50:50 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 15.7 min, Rt (minor) = 18.9 min.

[0192] (S,E)-N-(2,6-Dichlorobenzyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide (3r):

[0193]

[0194] 3r, colorless oil; 34 mg, 84% yield

[0195] ​​​​​13C NMR (101 MHz, CDCl3) δ 166.4, 164.2 (d, J = 252.1 Hz), 144.8, 139.2, 131.5, 130.3 (d, J = 3.8 Hz), 130.2 (d, J = 8.7 Hz), 129.3, 126.7, 116.7, 116.2 (d, J = 21.9 Hz), 66.5, 65.9, 64.9, 58.5, 58.5 ppm.

[0197] 19 19F NMR (377 MHz, CDCl3) δ -108.7 ppm.

[0198] HRMS (ESI, m / z): Calculated for C 20 H 21 Cl2FNO4 + [M + H] + : 428.0826, found: 428.0823.

[0199] [α] 2 D 5 = +5.776 (c = 1.0 in CHCl3).

[0200] HPLC analysis: 97:3 e.r. (Chiralcel ID, 50:50 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 16.3 min, Rt (minor) = 19.2 min.

[0201] (S,E)-2-((3-(4-Fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)-N-(naphthalen-1-ylmethyl)ethan-1-amine oxide (3s):

[0202]

[0203] 3s, colorless oil; 35 mg, 86% yield

[0204] 1H NMR(400MHz,CDCl3)δ8.30(d,J=8.6Hz,1H),7.96(d,J=8.3Hz,1H),7.91(d,J=8.2,1.4Hz,1H),7.79(d,J=7.2,1.3Hz,1H),7.67(d,J=16.0Hz,1H),7.62(t,J=8.5,6.8,1.4Hz,1H),7.56–7.46(m,4H),7.07(t,J=8.6Hz,2H),6.33(d,J=16.0Hz,1H),5.12(d,J=13.2Hz,1H),4.96(d,J=13.2Hz,1H),4.91–4.74(m,2H),4.23(ddd,J=13.2,7.2,2.5Hz,1H),4.09(ddd,J=13.2,6.2,2.6Hz,1H),3.62(t,J=5.0Hz,2H),3.56(ddd,J=9.7,7.1,3.6Hz,1H),3.48(ddd,J=13.0,6.2,2.5Hz,1H).

[0205] 13 C NMR(126MHz,Acetone-d6)δ166.6,164.6(d,J=249.3Hz),144.5,134.7(d,J=17.5Hz),134.0,131.6(d,J=3.3Hz),131.2(d,J=8.6Hz),130.7,129.2,128.0,127.1,126.4,126.3,125.6,118.3(d,J=2.3Hz),116.5(d,J=22.1Hz),68.3,65.6,65.2,59.3,58.4.

[0206] 19 F NMR(377MHz,CDCl3)δ-108.7ppm.

[0207] HRMS(ESI,m / z):Calculated for C 24 H 25 FNO4 + [M+H] + :410.1762,found:410.1762.

[0208] [α] 2 D 5 =+4.761(c=1.0in CHCl3).

[0209] HPLC analysis: 94:6 e.r. (Chiralcel ODH, 50:50 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 17.9 min, Rt (minor) = 12.2 min.

[0210] (S,E)-2-((3-(4-Fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)-N-(thiophen-2-ylmethyl)ethan-1-amine oxide (3t):

[0211]

[0212] 3t, colorless oil; 31 mg, 86% yield

[0213] 1 H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 16.0 Hz, 1H), 7.52 (dd, J = 8.6, 5.4 Hz, 2H), 7.46 (d, J = 5.2 Hz, 1H), 7.22 (dd, J = 3.5, 1.2 Hz, 1H), 7.13–7.01 (m, 3H), 6.38 (d, J = 16.0 Hz, 1H), 4.95–4.85 (m, 1H), 4.85–4.80 (m, 1H), 4.77 (d, J = 3.6 Hz, 2H), 4.21 (ddd, J = 13.2, 7.1, 2.6 Hz, 1H), 4.08 (ddd, J = 13.3, 6.0, 2.9 Hz, 1H), 3.77–3.62 (m, 1H), 3.54 (ddd, J = 13.8, 6.0, 3.4 Hz, 1H), 3.44 (ddd, J = 15.7, 9.8, 3.7 Hz, 2H).

[0214] 13 C NMR (101 MHz, CDCl3) δ 166.3, 164.2 (d, J = 252.3 Hz), 145.0, 131.9, 130.9, 130.24, 130.2 (d, J = 8.7 Hz), 129.6, 127.1, 116.6 (d, J = 2.5 Hz), 116.2 (d, J = 22.3 Hz), 66.7, 64.6, 64.0, 58.2, 58.0 ppm.

[0215] 19 F NMR (376 MHz, CDCl3) δ −108.6 ppm.

[0216] HRMS(ESI, m / z): Calculated for C 18 H 21 FNO4S + [M + H] + : 366.1170, found: 366.1163.

[0217] [α] 2 D 5 = +3.080 (c = 1.0 in CHCl3).<000077x>

[0218] HPLC analysis: 92:8 e.r. (Chiralcel ODH, 15:85 i-PrOH / n-Hexane, 1.0 mL / min), Rt(major) = 29.0 min, Rt(minor) = 24.5 min.

[0219] (S,E)-N-(2-((3-(4-Fluorophenyl)acryloyl)oxy)ethyl)-N-(2-hydroxyethyl)aniline oxide (3u):

[0220] 3u, colorless oil; 29 mg, 85% yield

[0221] 1 H NMR (400 MHz, CDCl3) δ 7.90 (dd, J = 8.7, 1.2 Hz, 2H), 7.55–7.47 (m, 2H), 7.46–7.38 (m, 3H), 7.34 (d, J = 16.1 Hz, 1H), 7.08 (td, J = 8.6 Hz, 2H), 6.02 (dd, J = 16.0, 0.6 Hz, 1H), 4.65 (td, J = 4.7, 1.4 Hz, 2H), 4.09 (ddd, J = 12.8, 6.3, 5.1 Hz, 1H), 4.12–4.01 (m, 1H), 3.99–3.83 (m, 1H), 3.83–3.69 (m, 2H), 3.62 (ddd, J = 1x.1, 10.0, 1.4 Hz, 1H).

[0222] 13 It should be noted that in the provided text, there are some tags like <000077x> which seem to be incorrect or incomplete in the original format. I've translated them as is while keeping the original structure. If there are specific corrections or clarifications for such tags, the translation can be adjusted accordingly.13C NMR (101 MHz, CDCl3) δ 166.3, 164.0 (d, J = 252.5 Hz), 149.5, 144.1, 130.3, 130.0 (d, J = 8.7 Hz), 129.4, 129.2, 121.7, 116.7, 116.2 (d, J = 22.0 Hz), 71.5, 71.0, 58.3, 57.7 ppm.

[0223] 19 19F NMR (377 MHz, Chloroform-d) δ -109.0 ppm.

[0224] HRMS (ESI, m / z): Calculated for C 19 H 21 19FNO4 + [M + H] + : 346.1449, found: 346.1447.

[0225] [α] 2 D 5 = +3.401 (c = 1.0 in CHCl3).

[0226] HPLC analysis: 92:8 e.r. (Chiralcel ID, 50:50 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 15.0 min, Rt (minor) = 12.1 min.

[0227] (S,E)-2-((3-(4-Fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)-N-phenethylethan-1-amine oxide (3v):

[0228]

[0229] 3v, colorless oil; 30 mg, 81% yield

[0230] 1H NMR(400MHz,CDCl3)δ7.7(d,J=16.0Hz,1H),7.5–7.4(m,2H),7.3–7.2(m,3H),7.2–7.2(m,2H),7.1(t,J=8.6Hz,2H),6.3(d,J=16.0Hz,1H),4.9–4.5(m,2H),4.1(m,2H),3.8–3.7(m,2H),3.7–3.6(m,2H),3.6–3.5(m,2H),3.3–3.1(m,1H),3.1–3.0(m,1H).

[0231] 13 C NMR(101MHz,CDCl3)δ166.3,164.2(d,J=252.2Hz),145.1,136.3,130.2(d,J=8.7Hz),130.1,129.0,128.7,127.2,116.4(d,J=2.6Hz),116.2(d,J=21.8Hz),68.3,65.7,64.8,58.2,57.8,30.1ppm.

[0232] 19 FNMR(377MHz,CDCl3)δ-108.5ppm.

[0233] HRMS(ESI,m / z):Calculated for C 21 H 25 FNO4 + [M+H] + :374.1762,found:374.1767.

[0234] [α] 2 D 5 =+3.601(c=1.0in CHCl3).

[0235] HPLC analysis:95:5e.r.(Chiralcel ODH,40:60i-PrOH / n-Hexane,0.3mL / min),Rt(major)=40.5min,Rt(minor)=36.5min.

[0236] (S,E)-N-(4-Chlorophenethyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide(3w):

[0237]

[0238] 3w, colorless oil; 35 mg, 85% yield

[0239] 1 H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 14.9 Hz, 1H), 7.41 (t, J = 7.2 Hz, 2H), 7.24–7.12 (m, 4H), 7.07 (t, J = 8.6 Hz, 2H), 6.24 (d, J = 14.9 Hz, 1H), 4.77 (dd, J = 18.1, 12.8 Hz, 2H), 4.14 (s, 2H), 3.78 (d, J = 5.9 Hz, 2H), 3.72–3.40 (m, 5H), 3.26–2.80 (m, 2H).

[0240] 13 C NMR (101 MHz, CDCl3) δ 166.2, 164.2 (d, J = 252.2 Hz), 145.2, 134.9, 133.1, 130.2 (d, J = 8.7 Hz), 130.1, 130.0, 129.1, 116.3 (d, J = 2.8 Hz), 116.3 (d, J = 21.8 Hz), 68.1, 65.8, 64.9, 58.2, 57.8, 29.2 ppm.

[0241] 19 F NMR (377 MHz, CDCl3) δ -108.3 ppm.

[0242] HRMS (ESI, m / z): Calculated for C 21 H 24 ClFNO4 + [M+H] + : 408.1372, found: 408.1376.

[0243] [α] 2 D 5 = +5.129 (c = 1.0 in CHCl3).

[0244] HPLC analysis: 92:8 e.r. (Chiralcel ASH, 50:50 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 10.0 min, Rt (minor) = 21.5 min.

[0245] (S,E)-N-(Cyclohexylmethyl)-2-((3-(4-fluorophenyl)acryloyl)oxy)-N-(2-hydroxyethyl)ethan-1-amine oxide(3x):

[0246]

[0247] 3x, colorless oil; 26.2 mg, 61% yield

[0248] 1 H NMR(400 MHz, CDCl3)δ7.69(d, J = 16.0 Hz, 1H), 7.61–7.39(m, 2H), 7.10(t, J = 8.6 Hz, 2H), 6.35(d, J = 16.0 Hz, 1H), 4.86–4.65(m, 2H), 4.13(ddd, J = 13.2, 7.0, 2.6 Hz, 1H), 4.05(ddd, J = 13.2, 6.1, 2.7 Hz, 1H), 3.75–3.58(m, 2H), 3.54(ddd, J = 12.9, 7.0, 2.8 Hz, 1H), 3.45(ddd, J = 12.9, 6.1, 2.6 Hz, 1H), 3.34–3.14(m, 2H), 2.08–1.81(m, 3H), 1.79–1.54(m, 3H), 1.38–1.23(m, 2H), 1.23–1.02(m, 3H).

[0249] 13 C NMR(101 MHz, CDCl3)δ166.4, 164.2(d, J = 252.2 Hz), 145.0, 130.2, 130.2(d, J = 8.4 Hz), 116.5(d, J = 2.2 Hz), 116.2(d, J = 21.9 Hz), 74.5, 65.6, 65.3, 58.3, 57.9, 33.3(d, J = 10.4 Hz), 33.3, 25.9(d, J = 2.1 Hz), 25.7 ppm.

[0250] 19 F NMR(377 MHz, CDCl3)δ - 108.6 ppm.

[0251] HRMS(ESI, m / z): Calculated for C 20 H 29 [[ID=2�]]FNO4 + [M + H] + : 366.2075, found: 366.2080.

[0252] [α] 2 D 5 = +3.737 (c = 1.0 in CHCl3).

[0253] HPLC analysis: 92:8 e.r. (Chiralcel ODH, 15:85 i-PrOH / n-Hexane, 0.5 mL / min), Rt (major) = 29.7 min, Rt (minor) = 24.5 min.

[0254] (S,E)-N-(2-((3-(4-Fluorophenyl)acryloyl)oxy)ethyl)-N-(2-hydroxyethyl)butan-1-amine oxide (3y):

[0255]

[0256] 3y, colorless oil; 24.1 mg, 63% yield

[0257] 1 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 16.0 Hz, 1H), 7.58–7.48 (m, 2H), 7.14–7.02 (m, 2H), 6.33 (d, J = 16.0 Hz, 1H), 4.87–4.59 (m, 2H), 4.32–4.01 (m, 2H), 3.68 (t, J = 5.0 Hz, 2H), 3.63–3.33 (m, 4H), 1.90–1.55 (m, 2H), 1.40 (q, J = 7.4 Hz, 2H), 0.96 (t, J = 7.3 Hz, 3H).

[0258] 13 13C NMR (101 MHz, CDCl3) δ 166.3, 164.2 (d, J = 252.4 Hz), 145.1, 130.2 (d, J = 8.1 Hz), 130.17 (d, J = 2.9 Hz), 116.4, 116.3 (d, J = 22.5 Hz), 67.3, 65.7, 64.4, 58.0, 57.4, 25.8, 20.0, 13.7 ppm. 19 19F NMR (377 MHz, Chloroform-d) δ -108.5 ppm.

[0259] HRMS (ESI, m / z): Calculated for C 17 H 25 FNO4+ [M+H] + : 326.1762, found: 326.1767.

[0260] [α] 2 D 5 = +5.716 (c = 1.0 in CHCl3).

[0261] HPLC analysis: 87:13 e.r. (Chiralcel ODH, 20:80 i-PrOH / n-Hexane, 1.0 mL / min), Rt (major) = 9.4 min, Rt (minor) = 8.0 min.

[0262] (S,E)-N-Benzyl-3-((3-(4-fluorophenyl)acryloyl)oxy)-N-(3-hydroxypropyl)propan-1-amine oxide (3z):

[0263]

[0264] 3z, colorless oil; 30 mg, 77% yield

[0265] 1 H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 16.0 Hz, 1H), 7.57–7.44 (m, 4H), 7.44–7.37 (m, 3H), 7.09 (t, J = 8.5 Hz, 2H), 6.31 (d, J = 16.0 Hz, 1H), 4.44 (d, J = 2.1 Hz, 2H), 4.39–4.10 (m, 2H), 3.86–3.55 (m, 2H), 3.44 (d, J = 6.7 Hz, 2H), 3.38–2.73 (m, 2H), 2.52–2.27 (m, 2H), 2.26–1.81 (m, 2H).

[0266] 13 C NMR (126 MHz, Acetone-d6) δ 166.0, 163.9 (d, J = 248.9 Hz), 143.4, 132.6, 131.4, 131.1, 130.5 (d, J = 8.6 Hz), 129.1, 128.2, 117.9 (d, J = 2.4 Hz), 115.9 (d, J = 22.1 Hz), 69.7, 66.7, 62.2, 62.0, 60.5, 28.1, 23.3 ppm.

[0267] 19FNMR (377MHz, CDCl3) δ-109.1ppm.

[0268] HRMS(ESI,m / z):Calculated for C 22 H 27 FNO4 + [M+H] + :388.1919,found:388.1928.

[0269] [α] 2 D 5 = +4.457 (c = 1.0 in CHCl3).

[0270] HPLC analysis: 85:15e.r. (Chiralcel ID, 50:50i-PrOH / n-Hexane, 1.0mL / min), Rt(major)=16.5min, Rt(minor)=13.6min.

[0271] Example 2

[0272] The present invention also provides a method for utilizing the chiral nitrogen oxide derivative 4 described in the above technical solution, comprising the following steps:

[0273]

[0274] Benzoic anhydride (37.8 mg, 0.167 mmol), KCO (28.8 mg, 0.209 mmol) and 3b (50.0 mg, 0.139 mmol) were dissolved in CHCl solution at 0°C, followed by the slow addition of DMAP (1.7 mg, 0.014 mmol). The reaction mixture was allowed to warm to room temperature and maintained overnight. After complete consumption of the starting material by TLC, the mixture was purified by flash chromatography using (CHCl / MeOH=20:1) to give a colorless oily compound (61.3 mg, 95%, 95:5 e.r.).

[0275] Shape and spectrum analysis of compound 4:

[0276] Colorless oil;

[0277] 11H NMR (400 MHz, CDCl3) δ 8.00 (dd, J = 8.3, 1.5 Hz, 2H), 7.65 (d, J = 16.1 Hz, 1H), 7.61 (dd, J = 7.4, 2.2 Hz, 2H), 7.56 (d, J = 7.5 Hz, 1H), 7.48 (dd, J = 8.7, 5.4 Hz, 2H), 7.46–7.38 (m, 5H), 7.06 (t, J = 8.6 Hz, 2H), 6.33 (d, J = 16.0 Hz, 1H), 5.08–4.92 (m, 2H), 4.85 (t, J = 5.1 Hz, 2H), 4.52 (d, J = 2.1 Hz, 2H), 3.63 (td, J = 5.4, 1.9 Hz, 2H), 3.58 (dd, J = 6.4, 4.1 Hz, 2H).

[0278] 13 13C NMR (101 MHz, CDCl3) δ 166.3, 166.2, 164.1 (d, J = 252.2 Hz), 144.9, 133.5, 132.5, 130.3, 130.2, 130.1, 129.9, 129.7, 129.6, 129.3, 129.0, 128.6, 128.0, 116.6 (d, J = 2.3 Hz), 116.3, 116.0, 73.3, 64.8, 64.7, 58.8, 58.4 ppm.

[0279] 19 19F NMR (377 MHz, CDCl3) δ -108.8 ppm.

[0280] HRMS (ESI, m / z): Calculated for C 27 H 27 FNO5 + [M + H] + : 464.1868, found: 464.1865.

[0281] [α] 2 D 5 = -6.584 (c = 1.0 in CHCl3).

[0282] HPLC analysis: 95:5 e.r. (Chiralcel ODH, 30:70 i-PrOH / n-Hexane, 0.5 mL / min), Rt (major) = 25.7 min, Rt (minor) = 30.3 min.

[0283] Example 3

[0284] The present invention also provides a method for utilizing the chiral nitrogen oxide derivative 5 described in the above technical solution, comprising the following steps:

[0285]

[0286] At 0 ° C, picolinic acid (12.0 mg, 0.097 mmol), DMAP (1.0 mg, 0.008 mmol) and 3b (30.0 mg, 0.081 mmol) were dissolved in CH2Cl2 solution, and EDCI (18.7 mg, 0.097 mmol) was slowly added. The reaction mixture was warmed to room temperature and kept overnight. After the starting material was completely consumed by TLC, the mixture was purified by flash chromatography using (CH2Cl2 / MeOH=20:1) to obtain the compound (23.7 mg, 61%, 95:5 e.r.) as a colorless oil.

[0287] Shape and spectrum analysis of compound 5:

[0288] Colorless oil

[0289] 1 H NMR (400MHz, CDCl3) δ8.72 (dd, J=5.0, 1.7Hz, 1H), 8.11 (d, J=7.8Hz, 1H), 7.84 (td ,J=7.8,1.8Hz,1H),7.70–7.61(m,3H),7.49(tt,J=8.1,4.4Hz,3H),7.47–7.38(m ,3H),7.13–6.99(m,2H),6.34(d,J=16.0Hz,1H),5.05(t,J=5.1Hz,2H),4.87(t,J =5.0Hz,2H),4.57(d,J=1.5Hz,2H),3.68(t,J=5.2Hz,2H),3.63(q,J=5.1Hz,2H).

[0290] 13 C NMR(101MHz, CDCl3)δ166.3,165.4(d,J=252.5Hz),164.9,150.0,147.4,144.8,137.2,132.7,132.4,130.2,130.1, 129.8(d,J=7.7Hz),128.9,127.3,125.4,116.7(d,J=2.3Hz),116.1(d,J=21.8Hz),73.5,64.9,64.2,59.6,58.5ppm.

[0291] 19FNMR (377MHz, CDCl3) δ-108.8ppm.

[0292] HRMS(ESI,m / z):Calculated for C 26 H 26 FN2O5 + [M+H] + :465.1820,found:465.1817.

[0293] [α] 2 D 5 =-8.729 (c = 1.0 in CHCl3).

[0294] HPLC analysis: 95:5e.r. (Chiralcel ODH, 30:70i-PrOH / n-Hexane, 0.2mL / min), Rt (major) = 118.6min, Rt (minor) = 104.5min.

[0295] Example 4

[0296] The present invention also provides a method for utilizing the chiral nitrogen oxide derivative 6 described in the above technical solution, comprising the following steps:

[0297]

[0298] At 0 ° C, 2- (4-chloro-2-methylphenoxy) acetic acid (20.0 mg, 0.099 mmol), DMAP (1.0 mg, 0.008 mmol) and 3b (30.0 mg, 0.083 mmol) were dissolved in CH Cl solution, and DCC (20.5 mg, 0.099 mmol) was slowly added. The reaction mixture was warmed to room temperature and kept overnight. After the raw material was completely consumed by TLC, the mixture was purified by flash chromatography using (CH Cl / MeOH = 20: 1) to obtain the compound (41.2 mg, 91%, 95: 5 e.r.) as a colorless oil.

[0299] Shape and spectrum analysis of compound 6:

[0300] Colorless oil;

[0301] 11H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 16.0 Hz, 1H), 7.56–7.48 (m, 4H), 7.47–7.38 (m, 3H), 7.13–6.98 (m, 4H), 6.58 (d, J = 8.6 Hz, 1H), 6.35 (d, J = 16.0 Hz, 1H), 4.86 (td, J = 4.9, 1.4 Hz, 2H), 4.83–4.72 (m, 2H), 4.66 (s, 2H), 4.43 (d, J = 12.8 Hz, 1H), 4.34 (d, J = 12.8 Hz, 1H), 3.65–3.44 (m, 2H), 3.40 (t, J = 5.1 Hz, 2H), 2.18 (s, 3H).

[0302] 13 13C NMR (101 MHz, CDCl3) δ 168.5, 166.3, 164.2 (d, J = 252.0 Hz), 154.4, 145.0, 132.4, 131.0, 130.2, 130.2, 130.0, 129.6, 129.1, 129.0, 126.5, 126.4, 116.5 (d, J = 2.3 Hz), 116.2 (d, J = 21.9 Hz), 111.9, 73.4, 65.6, 64.6, 64.5, 59.1, 58.3, 16.1 ppm.

[0303] 19 19F NMR (377 MHz, CDCl3) δ -10,8.6 ppm.

[0304] HRMS (ESI, m / z): Calculated for C 29 H[[ID=Y]] 29 ClFNO6 + [M + H] + : 542.1740, found: 542.1736.

[0305] [α] 2 D 5 = +7.331 (c = 1.0 in CHCl3).

[0306] HPLC analysis: 95:5 e.r. (Chiralcel ODH, 20:80 i-PrOH / n-Hexane, 0.5 mL / min), Rt (major) = 40.3 min, Rt (minor) = 36.4 min.

[0307] Example 5

[0308] The present invention also provides a method for utilizing the chiral nitrogen oxide derivative 7 described in the above technical solution, comprising the following steps:

[0309]

[0310] At 0 ° C, 3b (17.0 mg, 0.047 mmol) and Et3N (7.2 mg, 0.071 mmol) were dissolved in CH2Cl2 solution, followed by the slow addition of diphenylphosphonyl chloride (13.4 mg, 0.057 mmol). The reaction mixture was warmed to room temperature for 10 minutes. After complete consumption of the starting material by TLC, the mixture was purified by flash chromatography using (CH2Cl2 / MeOH=20:1) to obtain the compound (25.2 mg, 95%, 95:5 e.r.) as a colorless oil.

[0311] Shape and spectrum analysis of compound 7:

[0312] Colorless oil;

[0313] 1 H NMR(400MHz, Acetone-d6)δ7.97–7.80(m,4H),7.75(dd,J=8.7,5.6Hz,2H),7.74–7.63(m,3H),7.62–7.52(m,2H),7.50(q,J=7.9Hz,4H),7.44–7.2 8(m,3H),7.19(t,J=8.8Hz,2H),6.58(d,J=16.0Hz,1H),4.83–4.69(m,2H ),4.72–4.59(m,2H),4.60(s,2H),3.81–3.65(m,2H),3.63–3.59(m,2H).

[0314] 13 C NMR (101MHz, Acetone-d6) δ 166.7, 164.7 (d, J = 249.4Hz), 144.5, 133.8, 133.2 (d, J = 2.9Hz), 132.4 (d, J = 10.2Hz), 132.0, 131.8 (d, J = 3.2Hz), 131. 4(d,J=8.7Hz),129.8,129.6,129.5,128.8,118.5(d,J=2.1Hz),116.7(d ,J=22.0Hz),72.8,66.5(d,J=6.5Hz),65.6,59.9(d,J=5.1Hz),59.4ppm.

[0315] 31PNMR (162MHz, Acetone-d6) δ31.3ppm.

[0316] 19 FNMR (376MHz, Acetone-d6) δ-111.4ppm.

[0317] HRMS(ESI,m / z):Calculated for C 32 H 32 FNO5P + [M+H] + :560.1997,found:560.1995.

[0318] [α] 2 D 5 =-7.376 (c = 1.0 in CHCl3).

[0319] HPLC analysis: 95:5e.r. (Chiralcel ODH, 20:80i-PrOH / n-Hexane, 0.5mL / min), Rt (major) = 40.3min, Rt (minor) = 36.4min.

[0320] Example 6

[0321] The present invention also provides a method for utilizing the chiral nitrogen oxide derivative 10 described in the above technical solution, comprising the following steps:

[0322]

[0323] Under nitrogen protection, Zn (OTf) 2 (2.3 mg, 0.0062 mmol), ligand 3b (4.5 mg, 0.012 mmol) and Rb 2 CO 3 (2.9 mg, 0.012 mmol) were dissolved in acetone (0.5 mL) and stirred at room temperature for 2 hours. Next, a solution of 8 (0.062 mmol) in acetone (0.2 mL) was added with a syringe. The resulting mixture was then cooled to 0 ° C. After the mixture was stirred for 0.5 hours, allyl borate ester 9 (0.16 mmol) dissolved in acetone (0.3 mL) was added at one time. The reaction was monitored by TLC, evaporated in vacuo, and concentrated. The mixture was purified by flash chromatography using (PE / EtOAc = 3: 1) to obtain a compound with a white solid (12.1 mg, >99%, 61:39 e.r.).

[0324] Example 7

[0325] The present invention also provides a method for utilizing the chiral nitrogen oxide derivative 13 described in the above technical solution, comprising the following steps:

[0326]

[0327] Under nitrogen protection, In(OTf)3 (3.2 mg, 0.0057 mmol) and ligand 3b (4.1 mg, 0.012 mmol) were dissolved in THF (0.5 mL) and stirred at room temperature for 4 hours. Next, a solution of 11 (0.057 mmol) in THF (0.2 mL) was added with a syringe. The resulting mixture was then cooled to 0 ° C. After the mixture was stirred for 0.5 hours, a solution of 12 (0.14 mmol) in THF (0.3 mL) was added at one time. After the reaction was completed by TLC monitoring, the reaction solution was evaporated in vacuo. The mixture was purified by flash chromatography using (PE / EtOAc=20:1) to obtain a colorless oily compound (12.3 mg, 83%, 58:42 e.r.).

[0328] Example 8

[0329] This example provides antibacterial activity tests of related derivatives:

[0330] (1) Test method

[0331] The inhibitory activity of some target compounds against Xanthomonas oryzae pv.oryzae (Xoo.), the pathogen of rice bacterial blight, and Xanthomonas axonopodis pv.citri (Xac.), were tested using the turbidity method. The specific steps are as follows:

[0332] The compound was dissolved in 150.0 μL DMSO and diluted with 0.1% (v / v) Tween-20 to prepare a solution with a concentration of 100 μg / mL. 1.0 mL of the above solution was added to a non-toxic nutrient broth (Note: 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 tube. Then, 40.0 μL of NB solution containing Xanthomonas pv. Xoo. or Xac. 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 at 595 nm (OD 595 ) to monitor culture growth and expressed as corrected turbidity. The relative inhibition rate was calculated as follows:

[0333] I(%)=(Ctur-Ttur) / Ctur×100%

[0334] Ctur: turbidity value corrected for bacterial growth on untreated NB;

[0335] Ttur: turbidity value corrected for bacterial growth on treated NB;

[0336] I: relative inhibition rate.

[0337] Table 1. In vitro antibacterial activity of target compounds against Xoo. [a]

[0338]

[0339]

[0340] [a] Average of three tests; [b] The inhibitory activity of the commercial drug chlorpyrifos was used as a positive control.

[0341] Table 2. In vitro antibacterial activity of the target compounds against Xac. [a]

[0342]

[0343] [a] Average of three tests; [b] The inhibitory activity of the commercial drug thiophanate-methyl was used as a positive control.

[0344] The inhibitory activity of the target compounds against Xanthomonas oryzae was tested using the turbidity method with the commercial agent chloroquine as a positive control at test concentrations of 100 and 50 μg / mL (see Table 1). The test results showed that compounds 3b, 3f, 3j, and 3x had comparable activity to the positive agent chloroquine. Preliminary structure-activity relationships showed that: 1. The activity of nitrogen oxides against Xanthomonas oryzae was related to the substituents and the planar configuration of the molecule. R 1 Compounds with large ortho-substituents (e.g., 3o, 3p, and 3q) exhibited reduced activity against Xanthomonas oryzae compared to unsubstituted compound 3b (due to the impact of planarity and steric hindrance). Furthermore, compounds with skeletal transitions to thiophene (compound 3t) and carbon chain extensions (compound 3z) exhibited reduced activity against Xanthomonas oryzae, further demonstrating the importance of substituents and the molecular planarity in anti-Xanthomonas oryzae activity.

[0345] The hydroxyl group plays an important role in the activity of nitrogen oxides against bacterial blight of rice. For example, when the hydroxyl group of compound 3b is protected (4, 5, 6 and 7), the activity against bacterial blight of rice is significantly reduced.

[0346] We also tested the inhibitory activity of the target compounds against X. citri (see Table 2). The results showed that compounds 3i, 3q, 3x, 4, 6, and 7 exhibited comparable activity to the positive-acting drug chloroquine. Furthermore, the introduction of a benzoyl group (compound 4) and diphenylphosphine oxide (compound 6) into the hydroxyl group enhanced their activity against X. citri.

[0347] The above embodiment is only one of the preferred implementation methods of the present invention and should not be used to limit the scope of protection of the present invention. Any changes or modifications that have no substantive meaning made to the main design concept and spirit of the present invention, as long as the technical problems solved are still consistent with the present invention, should be included in the scope of protection of the present invention.

Claims

1. A chiral nitrogen oxide compound, characterized in that The chiral nitrogen oxide compound has the general structural formula of IIIa or IIIb in Formula 1: In formula 1, the nitrogen atom with * is a chiral nitrogen atom; R 1 It is one of benzyl, 4-methylphenyl, 4-isopropylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-nitrophenyl, 3-fluorophenyl, 3-chlorophenyl, 2-methoxyphenyl, 2-fluorophenyl, 2-bromophenyl, 2-bromo-5-fluorophenyl, 2,6-difluorophenyl, 2,6-dichlorophenyl, 2-fluoro-6-chlorophenyl, 1-naphthyl, 2-thienyl, phenyl, ethylphenyl, 4-chloroethylphenyl, cyclohexylmethyl, and butyl; R 2 It is one of phenyl, 2-fluorophenyl, 2-bromophenyl, 4-fluorophenyl, 4-bromophenyl and 4-methoxyphenyl.

2. The method for preparing a chiral nitrogen oxide compound according to claim 1, wherein: The preparation reaction formula of the compound IIIa is as shown in Formula 2: In formula 2, the structural formula of NHC F is shown in formula 3: In Formula 2, the structural formula of C-3 is shown in Formula 4:

3. The method for preparing a chiral nitrogen oxide compound according to claim 2, wherein: The preparation reaction formula of compound Ia is shown in Formula 5:

4. Use of the chiral nitrogen oxide compound according to claim 1 as a catalyst in the reaction described in Formula 6 or Formula 7: in, The structural formula of the chiral nitrogen oxide compound 3b is shown in Formula 8:

5. Use of the chiral nitrogen oxide compound according to claim 1 as an antibacterial agent against Xanthomonas oryzae and Xanthomonas aurantii.

6. A compound prepared using the chiral nitrogen oxide compound as claimed in claim 1 as a substrate, characterized in that: The structural formula of the compound is one of the structures shown in Formula 9:

7. Use of the compound according to claim 6 as an antibacterial agent against citrus canker bacteria.

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