Rutamycin derivative and use thereof

Abstract

Structured derivation is carried out on the basis of the structure of rutamycin, the present invention provides a series of novel compounds with certain physiological activity, and the compounds have a good inhibition effect on wheat fusarium head blight.

Description

Rutamycin derivatives and uses thereof Technical Field

[0001] The priority information of the present invention is as follows: Priority number 2023116800133, priority date December 8, 2023, invention name is Rutamycin derivatives and uses thereof, the disclosure of which is incorporated herein by reference. The present invention relates to the field of compounds, specifically to derivatives of Rutamycin and uses thereof. Background Art

[0002] Rutamycin (hereinafter referred to as RTM), also known as oligomycin D, is a macrolide antibiotic produced by Streptomyces sp. Its structural formula is as follows: Summary of the Invention

[0003] According to the structure of rutamycin, the present invention performs structural derivation on the basis of the structure and provides a series of new compounds with certain physiological activities.

[0004] Specifically, the compound represented by the following formula I or its pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate:

[0005] R1 is selected from -OH, -N3, -OC(=O)-benzene ring-(C0~C3 alkyl), -OS(=O)(=O)-benzene ring-Cl, -OC(=O)-benzene ring-O-(C0~C3 alkyl), -OC(=O)-benzene ring-benzene ring, -OC(=O)-benzene ring-N(CH3)(CH3), -OC(=O)-C(=O)-O-(C0~C3 alkyl), -OC(=O)-benzene ring-CF3, -OC(=O)-benzene ring-CCl3, -OC(=O)-(C0~C3 alkyl)-benzene ring, -OC(=O)-CH=CH-benzene ring, -OC(=O)-benzene ring-NO2, -OC(=O)-(C0~C3 alkyl), -OS(=O)(=O)-benzene ring-(C0-C4 alkyl), -OS(=O)(=O)-(C0~C3 alkyl).

[0006] R2 and R3 are selected from H, and a double bond is formed between the C to which R2 is connected and the C to which R3 is connected.

[0007] R4 is selected from -OH, -OC(=O)-benzene ring-(C0~C3 alkyl), -OC(=O)-benzene ring-benzene ring, -OC(=O)-C(=O)-O-(C0~C3 alkyl), -OC(=O)-benzene ring-CF3, -OC(=O)-benzene ring-CCl3, N3, -OC(=O)-C(=O)-O-(C0~C3 alkyl), -OS(=O)(=O)-(C0~C3 alkyl).

[0008] R5 is selected from =O or =N-NH2.

[0009] R6 is selected from -OH, -N3, -OC(=O)-phenyl ring-(C0~C3 alkyl), -OC(=O)-C(=O)-O-(C0~C3 alkyl).

[0010] R7 is selected from -OH, -OC(=O)-C(=O)-O-(C0-C3 alkyl);

[0011] R8, R9, R 10 With R 11 is selected from H, the C to which R8 is connected forms a double bond with the C to which R9 is connected, and R 10 Connected C and R 11 The C connected to R8 forms a double bond; or the C connected to R9 is connected to form a three-membered cyclic ether through O, R 10 Connected C and R 11 The connected C forms a double bond; or the C connected to R9 forms a double bond with R 10 The connected C forms a double bond, and the C connected to R8 forms a double bond with R 11 Connected C through Connection; or R9 connected to C and R 10 The connected C forms a double bond, and the C connected to R8 forms a double bond with R 11 Connected C through Connection; or R9 connected to C and R 10 The connected C forms a double bond, and the C connected to R8 forms a double bond with R 11 Connected C through Connection; or R9 connected to C and R 10 The connected C forms a double bond, and the C connected to R8 forms a double bond with R 11 Connected C through connect.

[0012] Furthermore, the above structure does not include rutamycin.

[0013] The present application also provides the use of the above-mentioned compound or its pharmaceutically acceptable salt, isotope variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate in preventing and controlling wheat fusarium.

[0014] In order to more clearly describe the content of this application, the terms involved are defined as follows:

[0015] As used herein, C1-Cn includes C1-C2, C1-C3, ..., C1-Cn, where n is an integer greater than one. The prefix of a substituent indicates the minimum and maximum number of carbon atoms in the substituent. For example, "C1-C6 alkyl" refers to a straight-chain or branched alkyl group containing one to six carbon atoms. In this application, "C0 alkyl" means no group.

[0016] The beneficial effects of the present invention are as follows: according to the structure of rutamycin, the present invention performs structural derivation on the basis thereof and provides a series of new compounds with certain physiological activities, which have good inhibitory effects on wheat fusarium. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] FIG1 is a mass spectrum characteristic diagram of Example 1;

[0018] FIG2 is a hydrogen nuclear magnetic spectrum of Example 1;

[0019] FIG3 is a carbon-NMR spectrum of Example 1;

[0020] FIG4 is a mass spectrum characteristic diagram of Example 2;

[0021] FIG5 is a hydrogen NMR spectrum of Example 2;

[0022] FIG6 is a C NMR spectrum of Example 2;

[0023] FIG7 is a mass spectrum characteristic diagram of Example 3;

[0024] FIG8 is a hydrogen NMR spectrum of Example 3;

[0025] FIG9 is a C NMR spectrum of Example 3;

[0026] FIG10 is a mass spectrum characteristic diagram of Example 4;

[0027] FIG11 is a hydrogen NMR spectrum of Example 4;

[0028] FIG12 is a C NMR spectrum of Example 4;

[0029] FIG13 is a mass spectrum characteristic diagram of Example 5;

[0030] FIG14 is a hydrogen NMR spectrum of Example 5;

[0031] Figure 15 is a C NMR spectrum of Example 5;

[0032] FIG16 is a mass spectrum characteristic diagram of Example 6;

[0033] FIG17 is a hydrogen NMR spectrum of Example 6;

[0034] Figure 18 is a carbon-NMR spectrum of Example 6;

[0035] FIG19 is a mass spectrum characteristic diagram of Example 7;

[0036] FIG20 is a hydrogen NMR spectrum of Example 7;

[0037] Figure 21 is a C NMR spectrum of Example 7;

[0038] FIG22 is a mass spectrum characteristic diagram of Example 8;

[0039] FIG23 is a hydrogen NMR spectrum of Example 8;

[0040] Figure 24 is a C-NMR spectrum of Example 8;

[0041] FIG25 is a mass spectrum characteristic diagram of Example 9;

[0042] FIG26 is a hydrogen NMR spectrum of Example 9;

[0043] Figure 27 is a C NMR spectrum of Example 9;

[0044] FIG28 is a mass spectrum characteristic diagram of Example 10;

[0045] FIG29 is a hydrogen NMR spectrum of Example 10;

[0046] Figure 30 is a C-NMR spectrum of Example 10;

[0047] FIG31 is a mass spectrum characteristic diagram of Example 11;

[0048] FIG32 is a H-NMR spectrum of Example 11;

[0049] FIG33 is a C NMR spectrum of Example 11;

[0050] FIG34 is a mass spectrum characteristic diagram of Example 12;

[0051] FIG35 is a H-NMR spectrum of Example 12;

[0052] FIG36 is a C-NMR spectrum of Example 12;

[0053] FIG37 is a mass spectrum characteristic diagram of Example 13;

[0054] FIG38 is a H-NMR spectrum of Example 13;

[0055] FIG39 is a C-NMR spectrum of Example 13;

[0056] FIG40 is a mass spectrum characteristic diagram of Example 14;

[0057] FIG41 is a H-NMR spectrum of Example 14;

[0058] FIG42 is a C NMR spectrum of Example 14;

[0059] FIG43 is a mass spectrum characteristic diagram of Example 15;

[0060] FIG44 is a H-NMR spectrum of Example 15;

[0061] Figure 45 is a C NMR spectrum of Example 15;

[0062] FIG46 is a mass spectrum characteristic diagram of Example 16;

[0063] FIG47 is a H-NMR spectrum of Example 16;

[0064] FIG48 is a C-NMR spectrum of Example 16;

[0065] FIG49 is a mass spectrum characteristic diagram of Example 17;

[0066] FIG50 is a H-NMR spectrum of Example 17;

[0067] FIG51 is a C-NMR spectrum of Example 17;

[0068] FIG52 is a mass spectrum characteristic diagram of Example 18;

[0069] FIG53 is a H-NMR spectrum of Example 18;

[0070] Figure 54 is a C-NMR spectrum of Example 18;

[0071] Figure 55 is a mass spectrum characteristic diagram of Example 19;

[0072] FIG56 is a H-NMR spectrum of Example 19;

[0073] Figure 57 is a C NMR spectrum of Example 19;

[0074] Figure 58 is a mass spectrum characteristic diagram of Example 20;

[0075] FIG59 is a H-NMR spectrum of Example 20;

[0076] Figure 60 is a C-NMR spectrum of Example 20;

[0077] Figure 61 is a mass spectrum characteristic diagram of Example 21;

[0078] FIG62 is a H-NMR spectrum of Example 21;

[0079] Figure 63 is a C-NMR spectrum of Example 21;

[0080] Figure 64 is a mass spectrum characteristic diagram of Example 22;

[0081] FIG65 is a H-NMR spectrum of Example 22;

[0082] Figure 66 is a C-NMR spectrum of Example 22;

[0083] Figure 67 is a mass spectrum characteristic diagram of Example 23;

[0084] FIG68 is a H-NMR spectrum of Example 23;

[0085] Figure 69 is a C NMR spectrum of Example 23;

[0086] Figure 70 is a mass spectrum characteristic diagram of Example 24;

[0087] FIG71 is a H-NMR spectrum of Example 24;

[0088] Figure 72 is a C NMR spectrum of Example 24;

[0089] Figure 73 is a mass spectrum characteristic diagram of Example 25;

[0090] FIG74 is a H-NMR spectrum of Example 25;

[0091] Figure 75 is the NMR carbon spectrum of Example 25. DETAILED DESCRIPTION

[0092] Example 1 Synthesis of Compound RTM-0215

[0093] Synthesis method: Dissolve rutamycin (400.0 mg, 0.515 mmol, 1.0 eq.) in dichloromethane (10 mL) and activate at 0°C for 20 min. Add benzoyl chloride (0.359 mL, 3.09 mmol, 6.0 eq.) and react at 25°C for 4 h. After the reaction, adjust the pH to acidic with 2NHCl, extract with water and dichloromethane (3 x 15 mL). The organic layer is washed with saturated brine (3 x 5 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product is purified by silica gel column chromatography (dichloromethane / methanol = 100 / 1) to obtain 374.4 mg (white solid), with a yield of 41.6%.

[0094] RTM-0215 ​​Synthesis Route

[0095] Mass spectrometry test: RTM-0215 ​​molecular formula C 58 H 80 O 13 , molecular weight 983 (Figure 1).

[0096] Nuclear magnetic hydrogen spectrum test: 1H NMR (400MHz, CDCl3) δ8.01–7.87(m,4H),7.54–7.44(m,2H),7.37(q,J=7.7Hz,4H),6.8 4(dd,J=15.7,9.7Hz,1H),5.92(dd,J=14.6,10.6Hz,1H),5.86–5.72(m,2H),5.62(dd,J =10.3,1.8Hz,1H),5.47–5.34(m,1H),5.34–5.19(m,2H),5.06(dd,J=14.9,9.6Hz,1H), 4.03–3.91(m,1H),3.86(d,J=4.1Hz,1H),3.80–3.72(m,1H),3.66(s,1H),3.65–3.56(m ,2H),3.21(s,1H),2.90(q,J=7.3Hz,1H),2.81–2.71(m,1H),2.27(dt,J=16.1,8.1Hz, 1H),2.15(dd,J=16.1,9.2Hz,2H),2.04–1.92(m,1H),1.88-1.84(m,2H),1.79–1.48(m, 10H),1.47–1.26(m,8H),1.13-1.06(m,9H),1.03–0.91(m,7H),0.90(d,J=6.9Hz,3H),0 .87–0.76(m,2H),0.79(d,J=6.9Hz,3H),0.70-0.62(m,1H),0.54(t,J=7.3Hz,3H) (Figure 2).

[0097] NMR carbon spectrum test: 13 C NMR (101MHz, CDCl3) δ216.57,165.00,164.72,164.11,147.69,137.10,132.27,131.70,131.49,129.90,1 29.20,128.66,128.61,128.55,128.52,127.86,127.49,127.31,121.69,96.41,82.14,73.22,72.30,71. 55,69.68,68.98,68.41,66.76,44.84,44.19,43.70,39.57,39.47,39.05,37.52,34.43,34.28,32.54,30.65,29.74,29.26,28.68,26.93,25.31,20.17,17.24,13.58,13.42,11.12,10.21,7.82,7.61,4.20 (Figure 3).

[0098] Example 2 Synthesis of Compound RTM-XZW-0304

[0099] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add o-chlorobenzenesulfonyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0100] RTM-XZW-0304 Synthesis Route

[0101] Mass spectrometry test: RTM-XZW-0304 molecular formula C 50 H 75 O 13 ClS, molecular weight 951 (Figure 4).

[0102] Nuclear magnetic hydrogen spectrum test: 1 H NMR (400MHz, CDCl3) δ7.90–7.80(m,1H),7.53–7.45(m,2H),7.38-7.30(m,1H),6.77(ddd,J=15.9,9.4Hz ,1H),6.03–5.80(m,3H),5.49–5.34(m,1H),5.25-5.19(m,3H),3.99–3.79(m,9H),2.82–2.76(m,1H),2.7 0–2.63(m,1H),2.20–0.71(m,22H),1.88(d,J=6.8Hz,3H),1.13(d,J=6.8Hz,3H),1.06(s,3H),1.02(d,J = 6.8Hz, 3H), 0.92 (d, J = 6.8Hz, 3H), 0.91 (d, J = 6.8Hz, 3H), 0.87 (d, J = 6.8Hz, 3H), 0.80–0.66 (m, 9H) (Figure 5).

[0103] NMR carbon spectrum test: 13C NMR (101MHz, CDCl3) δ214.55,164.17,147.92,137.28,134.70,133.45,131.84,131.51,130.98,129.2 2,129.04,127.96,125.81,121.57,96.43,84.18,82.04,71.91,71.55,69.83,69.03,66.34,63.62,52 .41,44.73,44.27,43.90,41.53,40.18,39.02,37.48,34.49,34.20,32.48,30.32,29.59,28.87,28.68,27.24,25.50,23.74,20.00,17.10,13.66,13.50,12.47,11.15,11.06,10.27,7.78,7.69,4.25 (Figure 6).

[0104] Example 3 Synthesis of Compound RTM-m-CPBA

[0105] Synthesis method: 200 mg, 0.13 mmol, 1.00 eq. of rutamycin and m-chloroperbenzoic acid (67.30 mg, 67.30 mmol, 1.50 eq.) were dissolved in dichloromethane (5 mL) and reacted at -17°C for 6 h. After completion of the reaction, the reaction solution was washed with 30 mL of saturated sodium bicarbonate solution, extracted with 50 mL of dichloromethane and 20 mL of water, and the organic phase was washed with 20 mL of saturated brine, dried over anhydrous sodium sulfate, and the solvent removed under reduced pressure. Column chromatography yielded a white powder.

[0106] RTM-m-CPBA synthetic route

[0107] Mass spectrometry test: RTM-m-CPBA molecular formula C 44 H 72 O 12 , molecular weight 792 (Figure 7).

[0108] Nuclear magnetic hydrogen spectrum test: 1H NMR (400MHz, CDCl3) δ6.54 (dd, J=15.6, 10.3Hz, 1H), 5.77 (d, J=15.6Hz, 1H), 5. 52(dd,J=15.5,7.8Hz,1H),5.38–5.20(m,2H),4.23(d,J=7.6Hz,1H),4.06(d,J =2.5Hz,1H),4.03–3.87(m,2H),3.78(dd,J=16.8,7.6Hz,2H),3.69(d,J=10.1H z,1H),3.66–3.55(m,2H),3.35(s,1H),3.19(s,1H),2.63(q,J=7.1Hz,2H),2.36 -2.29(m,1H),2.09-2.03(m,4H),1.93-1.84(m,2H),1.80(d,J=4.9Hz,1H),1.7 3–1.09(m,10H),1.27(d,J=7.3Hz,3H),1.18(d,J=7.3Hz,3H),1.12(d,J=7.3Hz, 3H),1.06(s,3H),1.01(d,J=6.4Hz,3H),1.00(d,J=6.4Hz,3H),0.98(d,J=6.4H z, 3H), 0.86 (d, J = 6.4Hz, 3H), 0.83 (d, J = 6.4Hz, 3H), 0.71 (t, J = 7.4Hz, 3H) (Figure 8).

[0109] NMR carbon spectrum test: 13 C NMR (101MHz, CDCl3) δ163.81,148.22,138.48,124.95,121.73,96.39,81.95,80 .57,72.51,72.18,71.75,69.40,68.75,66.54,63.76,45.16,45.03,42.48,41.4 7,40.71,38.92,34.66,33.78,33.37,29.66,28.81,28.56,27.24,26.39,26.27,25.50,23.70,19.20,16.46,16.08,13.06,10.62,10.37,7.62,7.25,4.84 (Figure 9).

[0110] Example 4 Synthesis of Compound RTM-317

[0111] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add m-methoxybenzoyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0112] RTM-317 Synthesis Route

[0113] Mass spectrometry test: RTM-317 molecular formula C 52 H 78 O 13 , molecular weight 910 (Figure 10).

[0114] Nuclear magnetic hydrogen spectrum test: 1 H NMR (400MHz, CDCl3) δ7.59(d,J=7.7Hz,1H),7.50(s,1H),7.36(dd,J=8.1Hz,1H),7.12(dd,J=8.1,2.7Hz,1H),6.91(dd,J=15.7,9.8Hz, 1H),6.08–5.91(m,2H),5.86(d,J=15.7Hz,1H),5.68(dd,J=10.3,2.2Hz,1H),5.50(dq,J=14.7,4.1Hz,1H),5.34–5.23(m,2H),4.10–3. 97(m,3H),3.95(s,1H),3.86(s,3H),3.77–3.65(m,2H),2.95(q,J=7.2Hz,1H),2.87–2.79(m,1H),2.39–0.81(m,25H),1.25(d,J=6.5Hz ,3H),1.87(s,3H),1.16(d,J=6.5Hz,6H),1.06–0.99(m,9H),0.91(d,J=6.9Hz,3H),0.89(d,J=6.9Hz,3H),0.83(t,J=7.4Hz,3H) (Fig. 11).

[0115] NMR carbon spectrum test: 13C NMR (101MHz, CDCl3) δ217.46,165.62,165.25,159.64,149.01,138.22,132.50,130.88,130.13,129.5 6,129.07,122.60,122.05,119.35,114.62,97.50,83.20,74.30,73.31,72.55,70.83,70.17,67.38,64 .64,55.47,55.44,46.05,45.21,44.78,42.63,40.67,40.60,38.52,35.45,35.42,33.57,31.48,30.95,30.64,29.83,28.41,26.51,24.76,21.20,18.35,14.57,14.40,12.13,11.26,8.84,8.58,5.18 (Figure 12).

[0116] Example 5 Synthesis of Compound RTM-XZW-0320

[0117] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.3 mmol, 3.0 eq.) in dichloromethane (5.0 mL), add biphenyl-4-carbonyl chloride (0.2 mmol, 2.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0118] RTM-XZW-0320 synthetic route

[0119] Mass spectrometry test: RTM-XZW-0320 molecular formula C 70 H 88 O 13 , molecular weight 1136 (Figure 13).

[0120] Nuclear magnetic hydrogen spectrum test: 1H NMR (400MHz, CDCl3) δ8.04(d,J=8.2Hz,2H),7.99(d,J=8.2Hz,2H),7.66-7.53(m ,8H),7.46–7.37(m,4H),7.42–7.30(m,2H),6.94(dd,J=15.7,9.5Hz,1H),5.99( dd,J=15.1,10.2Hz,1H),5.92–5.82(m,2H),5.71(dd,J=10.3,2.1Hz,1H),5.48– 5.22(m,4H),5.04(dd,J=14.9,9.5Hz,1H),4.06–3.96(m,1H),3.86(s,1H),3.78– 3.76(m,1H),3.69–3.62(m,3H),3.22(s,1H),2.99(q,J=7.2Hz,1H),2.85(qd,J= 6.8,2.1Hz,1H),2.31–2.24(m,1H),2.17–0.80(m,20H),1.33(d,J=7.7Hz,3H),1. 1(d,J=7.7Hz,9H),0.98(d,J=7.7Hz,3H),0.95(d,J=7.3Hz,3H),0.94(d,J=7.3H z, 3H), 0.91 (d, J = 7.3Hz, 3H), 0.81 (d, J = 7.3Hz, 3H), 0.55 (t, J = 7.3Hz, 3H) (Figure 14).

[0121] NMR carbon spectrum test: 13 C NMR (101MHz, CDCl3) δ216.65,164.85,164.58,164.09,147.67,145.10,144.51,139.03,138.97,137.12,131.47,129. 18,129.15,129.04,128.63,127.93,127.89,127.79,127.19,127.06,126.30,126.23,125.99,121.69,96.40,82.13,7 3.19,72.28,71.53,69.66,69.00,68.42,66.75,44.92,44.16,43.73,39.56,39.48,39.09,37.50,34.44,34.27,32.51,30.66,29.79,29.28,28.69,26.95,25.30,20.20,20.14,17.28,13.58,13.47,11.20,10.21,7.85,7.61,4.19 (Figure 15).

[0122] Example 6 Synthesis of Compound RTM-XZW-0318

[0123] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add 4-dimethylaminobenzoyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0124] RTM-XZW-0318 Synthesis Route

[0125] Mass spectrometry test: RTM-XZW-0318 molecular formula C 53 H 81 O 12 , molecular weight 923 (Figure 16).

[0126] Nuclear magnetic hydrogen spectrum test: 1 H NMR (400MHz, CDCl3) δ7.82–7.74(m,2H),6.87(dd,J=15.6,9.9Hz,1H),6.60–6.56(m,2H),5.98(ddd,J=14.7,10.4,1.6Hz,1H),5.87(dd,J=14 .9,10.5Hz,1H),5.77(d,J=15.6Hz,1H),5.61(dd,J=10.3,2.3Hz,1H),5.49–5.37(m,1H),5.27–5.17(m,2H),4.04–3.90(m,3H),3.88(s,1H), 3.76(s,2H),3.63(d,J=10.0Hz,1H),3.27(s,1H),2.97(s,6H),2.92–2 .84(m,1H),2.72(qd,J=6.9,2.2Hz,1H),2.29–0.80(m,24H),1.17(d,J = 6.2Hz, 3H), 1.11 (s, 3H), 1.07 (d, J = 6.2Hz, 6H), 0.97–0.90 (m, 9H), 0.85 (d, J = 6.7Hz, 3H), 0.85 (d, J = 6.7Hz, 3H), 0.76 (t, J = 7.4Hz, 3H) (Figure 17).

[0127] NMR carbon spectrum test: 13C NMR (101MHz, CDCl3) δ216.76,164.79,164.24,162.35,153.00,152.49,148.15,137.21,131.41,130. 39,129.03,128.04,121.49,115.11,114.59,96.47,82.12,72.21,72.07,71.52,69.72,69.23,66.24 ,63.54,45.22,44.36,43.45,41.60,39.83,39.80,39.06,37.47,34.42,34.38,32.53,30.55,30.07,29.60,28.79,27.43,25.47,23.77,20.17,17.46,13.55,13.44,11.17,10.25,7.81,7.62,4.17 (Figure 18).

[0128] Example 7 Synthesis of Compound RTM-LHY-0366

[0129] Synthesis method: Oligomycin D (200 mg, 0.26 mmol, 1.00 eq.) and N,N-dimethylaminopyridine (190.59 mg, 1.56 mmol, 6.00 eq.) were dissolved in dichloromethane (5 mL). Stirred at 0°C for 30 min, ethyl oxalyl chloride (191.12 mg, 1.56 mmol, 6.00 eq.) was slowly added dropwise, and the mixture was allowed to react at room temperature for 6 h. After completion of the reaction, the solvent was removed under reduced pressure, monitored by TLC. Column chromatography yielded 90.00 mg of the product (white solid, 45% yield).

[0130] RTM-LHY-0366 synthetic route

[0131] Mass spectrometry test: RTM-LHY-0366 molecular formula C 52 H 80 O 17 , molecular weight 976 (Figure 19).

[0132] H NMR test: 1H NMR (400MHz, Chloroform-d) δ6.84–6.65 (m, 1H), 6.02–5.89 (m, 2H), 5.89–5.73 (m, 1H), 5.50–5.34 (m, 2H), 5.22-5.04 (m, 3H), 4.35–4.18 (m, 4H), 4.04–3.86 (m, 1H), 3.83 (dd, J=11.9, 4.5Hz, 1H), 3.73–3.61 (m, 2H), 3.57 (s, 3H),3.20(d,J=7.4Hz,1H),2.77-2.27(m,1H),2.17–2.06(m,18H),1.34-1.26(m,13H),1.14-1.07(m,6H),1.04 (d, J = 6.9 Hz, 3H), 1.00 (d, J = 6.8 Hz, 3H), 0.96–0.93 (m, 6H), 0.87 (d, J = 6.9 Hz, 3H), 0.75 (t, J = 5.9 Hz, 6H) (Figure 20).

[0133] Nuclear magnetic carbon spectrum test: 13C NMR (101MHz, CDCl3) δ 216.00, 208.56, 163.97, 156.95, 156.42, 156.27, 147.58, 136.94, 131.44, 129.35, 128.04, 121.62, 96.47, 82.11, 72.03, 71.48, 69.53, 69.09, 67.11, 62.44, 62.06, 4 4.77,44.34,43.48,39.26,39.07,38.58,37.46,34.38,34.12,32.51,29.46,29.05,28.63,27.16,25.19,20.01,19.75,17.05,13.57,13.29,12.91,11.19,10.06,7.86,7.45,4.02 (Figure 21).

[0134] Example 8 Synthesis of Compound RTM-XZW-0366-2

[0135] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add o-methylbenzoyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0136] RTM-XZW-0366-2 Synthesis Route

[0137] Mass spectrometry test: RTM-XZW-0366-2 molecular formula C 52 H 78 O 12 , molecular weight 895 (Figure 22).

[0138] H NMR test: 1H NMR (400MHz, DMSO) δ7.78 (dd, J = 8.2, 1.5Hz, 1H), 7.49 (td, J = 7.5, 1.5Hz, 1H), 7.38–7.31 (m, 2H), 6.85 (dd, J = 15.7, 9.0Hz, 1H), 6.12–5.92 (m, 2H), 5.88 (d, J = 15.6Hz, 1H), 5.54(dd,J=9.8,2.0Hz,1H),5.43(ddd,J=14.8,10.6,4.2Hz,1H),5.25–5.13(m,3H), 4.45–4.36(m,2H),4.27(d,J=5.2Hz,1H),3.99–3.90(m,2H),3.84–3.75(m,2H),3.75 –3.69(m,1H),3.58(dd,J=7.5,1.4Hz,1H),2.83(tt,J=6.9,3.8Hz,1H),2.79–2.69(m ,1H),2.48(s,2H),2.38(q,J=7.9Hz,1H),2.04–1.90(m,4H),1.76(q,J=6.8,5.9Hz,1 H),1.68–1.64(m,1H),1.63–1.56(m,2H),1.55–1.49(m,2H),1.44–1.17(m,9H),1.10 (t,J=6.7Hz,6H),1.05–0.93(m,15H),0.91–0.84(m,6H),0.81(t,J=7.3Hz,3H) (Fig. 23).

[0139] Nuclear magnetic carbon spectrum test: 13C NMR (101MHz, DMSO) δ214.24, 166.69, 164.86, 150.54, 139.59, 136.70, 132.76, 132.52, 132.13, 131.33, 131.19, 130.33, 129.59, 128.76, 128.73, 128.64, 126.69, 126.55, 122.07, 97.04, 83.27, 74.43, 72.85, 71.99, 70.4 4,68.92,67.56,63.08,45.40,45.25,44.91,42.97,41.43,38.59,35.56,33.88,33.85,30.83,30.62,30.30,29.70,28.59,26.62,25.36,24.37,22.58,21.40,17.77,15.50,14.43,12.42,11.63,9.65,9.49,5.72 (Figure 24).

[0140] Example 9 Synthesis of Compound RTM-XZW-0401-1

[0141] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.3 mmol, 3.0 eq.) in dichloromethane (5.0 mL), add o-trifluoromethylbenzoyl chloride (0.2 mmol, 2.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0142] RTM-XZW-0401-1 Synthesis Route

[0143] Mass spectrometry test: The molecular formula of RTM-XZW-0401-1 is C60H78O13F6, and the molecular weight is 1120 (Figure 25).

[0144] Nuclear magnetic hydrogen spectrum test: 1H NMR (400MHz, CDCl3) δ7.86 (dd, J=7.2, 2.0Hz, 1H), 7.81 (dd, J=7.3, 1.8Hz, 1H), 7.75(dd,J=7.3,1.9Hz,2H),7.63-7.51(m,4H),6.89(dd,J=15.7,9.6Hz,1H),6 .07–5.82(m,3H),5.69(dd,J=10.5,2.1Hz,1H),5.55–5.43(m,1H),5.28–5.16( m,3H),3.96-3.88(m,1H),3.93(d,J=1.6Hz,1H),3.863.76(m,1H),3.74–3.67( m,2H),3.29(s,1H),3.00(q,J=7.3Hz,1H),2.87(qd,J=6.9,2.2Hz,1H),2.29–0 .08(m,23H),1.35(d,J=6.9Hz,3H),1.10(s,3H),1.07(d,J=6.9Hz,3H),1.05(d ,J=6.9Hz,3H),0.98(d,J=6.9Hz,3H),0.97(d,J=6.9Hz,3H),0.93(d,J=6.9Hz, 3H), 0.89 (d, J = 6.9 Hz, 3H), 0.79 (d, J = 6.9 Hz, 3H), 0.59 (t, J = 7.4 Hz, 3H) (Figure 26).

[0145] NMR carbon spectrum test: 13 C NMR (101MHz, CDCl3) δ216.91,165.06,164.46,164.12,147.86,137.25,131.51,130.91,130.71,130.30,13 0.10,129.73,129.56,129.14,129.03,127.83,125.68,121.57,96.58,82.08,73.88,72.16,71.55,70.33,6 9.69,69.17,66.97,44.76,44.14,43.71,39.26,39.20,38.57,37.53,34.16,34.05,32.49,30.68,29.45,29.06,28.68,28.53,26.84,25.32,20.06,19.49,17.08,13.52,13.10,11.10,10.09,7.80,7.53,4.21 (Figure 27).

[0146] Example 10 Synthesis of Compound RTM-XZW-0415

[0147] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add m-methoxybenzoyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0148] RTM-XZW-0415 synthetic route

[0149] Mass spectrometry test: RTM-XZW-0415 molecular formula C 53 H 78 O 12 , with a molecular weight of 908 (Figure 28).

[0150] Nuclear magnetic hydrogen spectrum test: 1 H NMR (400MHz, CDCl3) δ7.23-7.19(m,2H),7.15-7.10(m,3H),6.75(dd,J=15.7,9.8H z,1H),5.97(dd,J=14.1,11.0Hz,1H),5.87(dd,J=14.8,10.4Hz,1H),5.77(d,J=15 .7Hz,1H),5.49–5.36(m,1H),5.31(dd,J=10.3,2.0Hz,1H),5.28–5.14(m,2H),4.0 5–3.97(m,1H),3.94(d,J=10.4Hz,1H),3.85(s,1H),3.82–3.71(m,2H),3.66(s,1H ),3.60(d,J=10.1Hz,1H),3.14(s,1H),2.91-2.80(m,2H),2.76(q,J=7.3Hz,1H),2 .70–2.60(m,1H),2.61–2.47(m,2H),2.32–1.94(m,4H),1.87(d,J=1.8Hz,3H),1.7 5–1.10 (m, 16H), 1.17 (d, J = 6.2 Hz, 3H), 1.10 (d, J = 6.6 Hz, 3H), 1.07 (s, 3H), 0.96 (d, J = 6.8 Hz, 3H), 0.94-0.90 (m, 6H), 0.86 (d, J = 7.0 Hz, 3H), 0.79-0.74 (m, 9H) ( FIG. 29 ).

[0151] NMR carbon spectrum test: 13C NMR (101MHz, CDCl3) δ217.35,172.17,165.18,148.93,140.23,138.21,132.48,130.11,129.04, 128.48,128.22,126.30,122.55,97.46,83.11,73.52,73.25,72.54,70.78,70.15,67.39,64.63, 45.99,45.02,44.87,42.67,40.46,40.22,38.52,35.49,35.36,33.56,31.44,30.87,30.72,30.66,29.87,28.38,26.55,24.77,21.08,18.29,14.55,14.18,12.12,11.26,8.70,8.47,5.10 (Figure 30).

[0152] Example 11 Synthesis of Compound RTM-XZW-0419

[0153] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add m-methoxybenzoyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0154] RTM-XZW-0419 synthetic route

[0155] Mass spectrometry test: RTM-XZW-0419 molecular formula C 53 H 78 O 12 , molecular weight 906 (Figure 31).

[0156] Nuclear magnetic hydrogen spectrum test: 1HNMR(400MHz, CDCl3)δ7.59(d,J=16.0Hz,1H),7.52–7.42(m,2H),7.37–7.25(m,3H),6.82 (dd,J=15.7,9.8Hz,1H),6.33(d,J=16.0Hz,1H),5.98(dd,J=14.2,11.0Hz,1H),5.88(dd, J=14.8,10.4Hz,1H),5.79(d,J=15.7Hz,1H),5.49(dd,J=10.3,2.0Hz,1H),5.47–5.37(m, 1H),5.26-5.17(m,2H),4.06-3.82(m,4H),3.77-3.74(m,1H),3.73(s,1H),3.67(d,J=10.0 Hz,1H),3.22(s,1H),2.85(q,J=7.3Hz,1H),2.72(dq,J=6.7,3.4Hz,1H),2.33–2.23(m,1H ),2.23–2.09(m,2H),2.03(tt,J=13.2,4.1Hz,1H),1.91-1.86(m,2H),1.85–1.76(m,1H), 1.74–0.90(m,16H),1.17(d,J=6.2Hz,3H),1.11(d,J=6.5Hz,6H),1.05(d,J=6.8Hz,3H),0 .98-0.92(m,9H),0.85(d,J=7.0Hz,3H),0.81(d,J=6.9Hz,3H),0.78(t,J=7.0Hz,3H (Figure 32).

[0157] NMR carbon spectrum test: 13 C NMR (101MHz, CDCl3) δ216.65,165.07,164.21,148.00,144.69,137.24,133.18,131.48,129.52,12 9.10,128.05,127.89,127.23,121.58,116.24,96.48,82.16,72.71,72.28,71.56,69.79,69.17,66 .36,63.61,45.06,44.11,43.77,41.65,39.59,37.52,34.47,34.40,32.57,30.48,29.95,29.65,28.84,27.39,25.91,25.52,23.77,20.15,17.35,13.56,13.39,11.13,10.26,7.74,7.57,4.14 (Figure 33).

[0158] Example 12 Synthesis of Compound RTM-LHY-0328

[0159] Synthesis method: Rutamycin (200 mg, 0.26 mmol, 1.00 eq.), triphenylphosphine (410.00 mg, 1.56 mmol, 6.00 eq.), and p-nitrobenzoic acid (260.71 mg, 1.56 mmol, 6.00 eq.) were dissolved in tetrahydrofuran (5 mL). Under argon, the mixture was stirred at 0°C for 30 min. Diisopropyl azodicarboxylate (315.43 mg, 1.56 mmol, 6.00 eq.) was slowly added dropwise and the mixture was allowed to react at room temperature for 6 h. After completion of the reaction, the solvent was removed under reduced pressure and purified by column chromatography to yield a white powder.

[0160] RTM-LHY-0328 synthetic route

[0161] Mass spectrometry test: RTM-LHY-0328 molecular formula C 51 H 75 NO 14 , molecular weight 925 (Figure 34).

[0162] Nuclear magnetic hydrogen spectrum test: 1HNMR(400MHz, CDCl3)δ8.32(d,J=8.9Hz,2H),8.27–8.19(m,2H),6.63(dd,J=15.6,9.8Hz,1H),6 .05(dd,J=14.3,10.8Hz,1H),5.96(dd,J=14.7,10.4Hz,1H),5.82(d,J=15.7Hz,1H),5.50(ddd, J=14.6,10.5,4.0Hz,1H),5.38–5.15(m,3H),4.03–3.92(m,2H),3.84(t,J=5.5Hz,1H),3.78(d, J=10.1Hz,1H),3.71(d,J=8.9Hz,1H),3.67–3.56(m,1H),3.48(d,J=1.9Hz,1H),3.35(s,1H),2. 81(dt,J=9.6,5.2Hz,1H),2.78–2.72(m,1H),2.53(d,J=4.1Hz,1H),2.41(td,J=9.8,6.4Hz,1H) ,2.22(d,J=13.6Hz,1H),2.17–1.86(m,5H),1.63-0.9(m,15H),1.45(d,J=6.2Hz,3H),1.20(d,J =6.5Hz,3H),1.17(s,3H),1.12(d,J=6.7Hz,3H),1.11(d,J=7.2Hz,3H),1.07(d,J=6.9Hz,3H),1 .03(d,J=6.5Hz,3H), 0.97(d,J=6.9Hz,3H), 0.81(d,J=6.9Hz,3H), 0.76(t,J=7.4Hz,3H) (Figure 35).

[0163] Nuclear magnetic carbon spectrum test: 13C NMR (101MHz, CDCl3) δ164.73, 164.15, 150.50, 148.58, 137.12, 136.11, 132.33, 130.69, 129.73, 123.55, 122.64, 97.49, 83.03, 77.22, 73.07, 72.64, 72.37, 70.90, 70.56, 69.93, 68.36, 4 6.78,45.81,45.62,41.87,39.98,39.66,38.50,35.50,35.24,33.55,31.56,30.55,29.91,29.68,28.33,26.27,21.06,20.68,17.71,14.49,13.90,11.99,11.09,9.52,8.34,5.25 (Figure 36).

[0164] Example 13 Synthesis of Compound RTM-W-XZW-0474-1

[0165] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and N-phenylmaleimide (1 mmol, 10.0 eq.) in toluene (5.0 mL) and react at 105°C for 24 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0166] RTM-W-XZW-0474-1 Synthesis Route

[0167] Mass spectrometry test: RTM-W-XZW-0474-1 molecular formula C 48 H 75 O 13 N, molecular weight 873 (Figure 37).

[0168] Nuclear magnetic hydrogen spectrum test: 1 H NMR (400MHz, CDCl3) δ8.45 (s, 1H), 6.79 (dd, J = 15.6, 6.9Hz, 1H), 5.85-5.81 (m,2H),5.65-5.6-(m,1H),5.33(dt,J=10.7,5.2Hz,1H),4.15–4.02(m,2H) ,4.04–3.90(m,2H),3.83(t,J=5.8Hz,1H),3.63(d,J=9.8Hz,1H),3.55-3.4 9(m,1H),3.44(s,2H),3.38(s,1H),3.36–3.29(m,1H),3.16–3.08(m,1H),2. 64(t,J=7.3Hz,1H),2.59–2.49(m,1H),2.32(d,J=5.9Hz,3H),2.21–1.91(m ,7H),1.90–0.81(m,15H),1.18(s,3H),1.17(d,J=7.2Hz,3H),1.15(d,J=7. 2Hz,3H),1.10(d,J=7.7Hz,6H),1.08(d,J=7.2Hz,3H),1.01(d,J=6.5Hz,3H ), 0.86 (d, J = 6.9 Hz, 3H), 0.82 (d, J = 6.9 Hz, 3H), 0.78 (t, J = 7.4 Hz, 3H) (Figure 38).

[0169] Nuclear magnetic resonance carbon spectrum test: 13C NMR (101MHz, CDCl3) δ177.44, 176.52, 165.06, 147.94, 132.42, 131.06, 120.95, 96.78, 82.02, 72.68, 70.54, 70.07, 69.72, 66.38, 63.15, 47.30, 44.53, 42.10, 42.01, 41.16, 40. 82,39.08,37.60,35.49,34.45,33.39,33.07,32.09,29.71,28.78,28.68,25.59,25.39,24.75,23.94,21.49,19.99,14.70,13.79,13.45,10.15,9.37,8.75,7.79,3.80 (Figure 39).

[0170] Example 14 Synthesis of Compound RTM-W-XZW-0511-1

[0171] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and N-phenylmaleimide (1 mmol, 10.0 eq.) in toluene (5.0 mL) and react at 105°C for 24 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0172] RTM-W-XZW-0511-1 Synthesis Route

[0173] Mass spectrometry test: RTM-W-XZW-0511-1 molecular formula C 49 H 77 O 13 N, molecular weight 887 (Figure 40).

[0174] Nuclear magnetic hydrogen spectrum test: 1H NMR (400MHz, CDCl3) δ6.80 (dd, J=15.6, 6.6Hz, 1H), 5.83 (dd, J=15.6, 1.2Hz, 1H), 5.77(dd,J=7.7,4.5Hz,1H),5.57(dd,J=6.0,2.9Hz,1H),5.39–5.28(m,1H),4.17 -4.11(m,2H),3.99-3.91(m,2H),3.86(t,J=6.4Hz,1H),3.62(d,J=9.6Hz,1H),3. 51(dd,J=9.6,6.9Hz,1H),3.45–3.37(m,2H),3.33–3.26(m,2H),3.12–3.03(m,1H) ,2.79(s,3H),2.64(q,J=7.2Hz,1H),2.53(q,J=7.2Hz,1H),2.46–2.23(m,3H),2. 22–0.9(m,22H),1.18(d,J=6.2,Hz,3H),1.17(d,J=6.2,Hz,3H),1.17(s,3H),1.1 6(d,J=7.2,Hz,3H),1.11(d,J=7.2,Hz,3H),1.10(d,J=6.7Hz,3H),1.08(d,J=6.9 Hz, 3H), 0.86 (d, J = 6.9 Hz, 3H), 0.83 (d, J = 6.9 Hz, 3H), 0.77 (t, J = 7.3 Hz, 3H) (Figure 41).

[0175] NMR carbon spectrum test: 13 C NMR (101MHz, CDCl3) δ222.90,220.00,178.18,177.42,166.09,148.91,133.35,131.99,121.90 ,97.86,82.97,73.68,71.62,71.50,71.15,70.61,67.38,63.94,48.39,45.49,42.05,41.81,41 .79,41.75,40.14,38.50,36.65,35.49,34.51,33.75,33.13,30.78,29.84,29.69,26.64,26.45,25.99,25.03,24.45,22.40,20.98,15.56,14.71,14.50,11.10,10.38,9.45,8.76,4.74 (Figure 42).

[0176] Example 15 Synthesis of Compound RTM-W-XZW-0526-1

[0177] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and N-benzylmaleimide (1 mmol, 10.0 eq.) in toluene (5.0 mL) and react at 105°C for 24 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0178] RTM-W-XZW-0526-1 Synthesis Route

[0179] Mass spectrometry test: RTM-W-XZW-0526-1 molecular formula C 55 H 81 O 13 N, molecular weight 963 (Figure 43).

[0180] Nuclear magnetic hydrogen spectrum test: 1 H NMR (400MHz, CDCl3) δ7.25(s,5H),6.86(dd,J=15.6,6.3Hz,1H),5.89(d,J=15.6Hz,1H),5.80(d,J=7.9Hz,1H),5.62(d,J=7.7Hz,1H),5.46–5.32(m,1H ),4.53(s,2H),4.23(d,J=4.6Hz,1H),4.18(d,J=10.7Hz,1H),3.99(d,J=9. 1Hz,2H),3.91(s,1H),3.68(d,J=9.4Hz,1H),3.62–3.51(m,1H),3.47(d,J=2 .4Hz,2H),3.39-3.36(m,1H),3.29(s,1H),3.22–3.12(m,1H),2.69(q,J=7. 2Hz,1H),2.59(q,J=6.9Hz,1H),2.54–2.29(m,4H),2.18-1.11(m,18H),1.24 (s,12H),1.18(d,J=6.8Hz,3H),1.15(d,J=7.6Hz,3H),1.10(d,J=2.7Hz,6H ), 0.93 (d, J = 6.5Hz, 3H), 0.89 (d, J = 6.6Hz, 3H), 0.83 (t, J = 6.9Hz, 3H) (Figure 44).

[0181] NMR carbon spectrum test: 13C NMR (101MHz, CDCl3) δ177.79,177.02,166.03,148.86,135.73,133.37,132.02,128.56,128.21,127 .74,121.92,97.82,83.00,77.22,73.72,71.55,71.49,71.11,70.61,67.31,63.89,48.38,45.48,4 2.21,42.09,41.76,41.71,40.31,38.50,36.55,35.47,34.45,33.89,33.25,30.76,29.80,29.68,26.65,26.46,25.99,25.04,22.40,20.95,15.57,14.79,14.52,11.11,10.36,9.48,8.78,4.76 (Figure 45).

[0182] Example 16 Synthesis of Compound RTM-WC-LHY-0410

[0183] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add m-methoxybenzoyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0184] RTM-WC-LHY-0410 synthetic route

[0185] Mass spectrometry test: RTM-WC-LHY-0410 molecular formula C 44 H 68 N 12 O7, molecular weight 876 (Figure 46).

[0186] Nuclear magnetic hydrogen spectrum test: 1H NMR (400MHz, CDCl3) δ6.66 (dd, J=15.6, 8.0Hz, 1H), 6.03–5.85 (m, 2H), 5.80 (d, J=15.6Hz,1H),5.64(dd,J=14.2,7.3Hz,1H),5.28(dd,J=14.5,8.8Hz,1H),5.11 (dt,J=12.0,4.8Hz,1H),3.88(dd,J=9.9,8.6Hz,1H),3.83–3.73(m,3H),3.55(d ,J=8.4Hz,1H),3.46(dd,J=14.2,6.2Hz,1H),3.08-3.01(m,2H),2.63(q,J=7.5H z,1H),2.35(dd,J=16.0,7.5Hz,1H),2.19–1.90(m,7H),1.85-1.74(m,1H),1.7 5–1.29(m,19H),1.26(d,J=6.5Hz,3H),1.18(d,J=7.5Hz,3H),1.14(d,J=6.0Hz, 3H),1.12(d,J=6.8Hz,3H),1.06(d,J=7.0Hz,3H),0.97(s,3H),0.84(d,J=7.0Hz ,3H), 0.80(t,J=5.7Hz,3H), 0.76(d,J=6.9Hz,3H), 0.68(d,J=6.9Hz,3H) (Fig. 47).

[0187] Nuclear magnetic hydrogen spectrum test: 13 C NMR (101 MHz, Chloroform-d) δ 164.39, 147.74, 134.90, 130.59, 130.00, 121.13, 96.52, 84.86, 82.12, 72.03, 70.24, 67.20, 53.63, 48.91, 48.51, 44.93, 42.48, 38.40, 37.64, 37.06, 34.52, 33.10, 32.65, 28.81, 28.11, 27.20, 25.23, 19.13, 16.87, 15.66, 12.55, 12.42, 11.01, 10.68, 9.89, 6.97, 3.55 ( FIG. 48 ).

[0188] Example 17 Synthesis of Compound RTM-W-XZW-0458

[0189] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add benzoyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0190] RTM-W-XZW-0458 Synthesis Route

[0191] Mass spectrometry test: RTM-W-XZW-0458 molecular formula C 51 H 76 O 12 , molecular weight 880 (Figure 49).

[0192] Nuclear magnetic hydrogen spectrum test: 1 HNMR (400MHz, CDCl3) δ8.02(d,J=7.2Hz,2H),7.60(t,J=7.4Hz,1H),7.47(t,J=7.7Hz,2H ),6.94(dd,J=15.7,9.9Hz,1H),6.07(dd,J=14.5,11.0Hz,1H),5.97(dd,J=14.8,10.5Hz ,1H),5.88(d,J=15.6Hz,1H),5.72(dd,J=10.3,1.9Hz,1H),5.60–5.46(m,1H),5.39–5.2 3(m,2H),4.13–4.00(m,3H),3.97(s,1H),3.85(d,J=9.1Hz,1H),3.75(s,1H),3.71(d,J=1 0.0Hz,1H),3.32(s,1H),2.98(q,J=7.3Hz,1H),2.85(qd,J=7.3,2Hz,1H),2.42–2.17(m, 3H),2.15-2.05(m,3H),2.05-0.80(m,17H),1.26(d,J=6.4Hz,3H),1.21(s,3H),1.18(d,J =3.3Hz,3H),1.17(d,J=2.9Hz,3H),1.06(d,J=7.1Hz,3H),1.04(d,J=5.8Hz,3H),1.03(d , J=7.2Hz, 3H), 0.94 (d, J=7.1Hz, 3H), 0.92 (d, J=7.0Hz, 3H), 0.85 (t, J=7.4Hz, 3H) (Figure 50).

[0193] Nuclear magnetic carbon spectrum test: 13C NMR (101MHz, CDCl3) δ217.55, 165.76, 165.24, 149.03, 138.28, 133.30, 132.49, 130.11, 129.69, 129.58, 129.08, 128.52, 122.59, 97.50, 83.20, 74.21, 73.31, 72.53, 70.81, 70.19, 67.36, 64.62,46.09,45.21,44.76,42.64,40.66,40.61,38.53,35.42,33.57,31.51,30.98,30.65,29.84,28.42,26.52,24.78,21.19,18.37,14.58,14.41,12.15,11.27,8.85,8.59,5.20 (Figure 51).

[0194] Example 18 Synthesis of Compound RTM-W-XZW-0539

[0195] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add acetyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid (Figure 69).

[0196] RTM-W-XZW-0539 Synthesis Route

[0197] Mass spectrometry test: RTM-W-XZW-0539 molecular formula C 46 H 74 O 12 , molecular weight 818 (Figure 52).

[0198] Nuclear magnetic hydrogen spectrum test: 1HNMR (400MHz, CDCl3) δ6.81(dd,J=15.7,9.8Hz,1H),6.04(dd,J=14.2,11.0Hz,1H),5.94(dd,J=14.8,10.4Hz,1H),5.83(d,J=15.7Hz,1H),5.56- 5.48(m,1H),5.38(dd,J=10.3,1.9Hz,1H),5.29-5.23(m,2H),4.09–4.0 3(m,1H),4.01(d,J=10.4Hz,1H),3.94-3.88(m,1H),3.91–3.79(m,2H),3 .78(d,J=1.4Hz,1H),3.70(d,J=10.1Hz,1H),3.27(s,1H),2.84(q,J=7. 5Hz,1H),2.73(qd,J=6.9,2.0Hz,1H),2.39–2.04(m,5H),2.03(s,3H),2. 02-0.80(m,18H),1.24(d,J=6.8Hz,3H),1.17(d,J=6.8Hz,3H),1.15(s, 3H), 1.05 (d, J = 6.8 Hz, 3H), 1.01 (d, J = 6.7 Hz, 3H), 1.00 (d, J = 6.7) (Figure 53).

[0199] NMR carbon spectrum test: 13 C NMR (101MHz, CDCl3) δ217.80,170.45,165.16,148.89,138.20,132.47,130.11,129.05, 122.54,97.46,83.11,73.61,73.26,72.53,70.77,70.15,67.36,64.60,46.06,44.99,44 .82,42.64,40.43,40.20,38.50,35.44,35.35,33.56,31.47,30.92,30.64,29.83,28.39,26.51,24.77,21.10,20.70,18.24,14.55,14.32,12.13,11.26,8.65,8.48,5.09 (Figure 54).

[0200] Example 19 Synthesis of Compound RTM-W-XZW-0578-2

[0201] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add phenylacetyl chloride (0.2 mmol, 2.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0202] RTM-W-XZW-0578-2 Synthesis Route

[0203] Mass spectrometry test: RTM-W-XZW-0578-2 molecular formula C 69 H 94 O 13 , molecular weight 1130 (Figure 55).

[0204] Nuclear magnetic hydrogen spectrum test: 1 HNMR (400MHz, CDCl3) δ7.36–6.94(m,15H),6.69(dd,J=15.7,9.8Hz,1H),6.00–5.80(m,2H),5.73(d,J=15.7Hz,1H),5.48–5.36(m,1H),5.33(d,J =10.2Hz,1H),5.22-5.14(m,3H),5.01–4.81(m,1H),4.70(d,J=1.7Hz,1 H),3.82(s,1H),3.80–3.54(m,7H),3.53–3.44(m,3H),3.35(dd,J=14.6, 14.6Hz,1H),3.15(s,1H),2.73(q,J=7.1Hz,1H),2.68–2.55(m,1H),2.3 2–0.80(m,19H),1.20(d,J=6.6Hz,6H),1.06(s,3H),1.03(d,J=6.6Hz,3H ), 0.94 (d, J = 6.6Hz, 3H), 0.92 (d, J = 6.6Hz, 3H), 0.89 (d, J = 7.3Hz, 3H), 0.76 (d, J = 7.2Hz, 3H), 0.74 (d, J = 7.3Hz, 3H), 0.71 (t, J = 7.3Hz, 3H) (Figure 56).

[0205] NMR carbon spectrum test: 13C NMR (101MHz, CDCl3) δ216.54,199.93,172.95,169.87,166.82,164.14,147.84,136.92,135.55,132.55,132.36,131.42,130.40,1 29.80,129.25,128.59,128.54,128.35,128.12,127.95,127.80,127.62,127.53,127.37,127.21,126.98,126.22,126.17,126.05 ,125.97,125.63,121.48,96.56,82.06,72.81,72.13,71.54,69.55,69.21,47.38,44.80,43.99,43.82,40.28,39.39,38.27,37.50,34.21,32.51,30.42,29.19,28.68,27.31,20.10,19.57,17.12,13.53,13.04,11.20,11.15,9.91,9.79,7.64,7.49,4.05 (Figure 57).

[0206] Example 20 Synthesis of Compound RTM-W-XZW-0621-1

[0207] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and N-cyclohexanemaleimide (1 mmol, 10.0 eq.) in toluene (5.0 mL) and react at 105°C for 24 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0208] RTM-W-XZW-0621-1 Synthesis Route

[0209] Mass spectrometry test: RTM-W-XZW-0621-1 molecular formula C 54 H 85 O 13 N, molecular weight 955 (Figure 58).

[0210] Nuclear magnetic hydrogen spectrum test: 1HNMR(400MHz, CDCl3) δ6.83(dd,J=15.6,6.2Hz,1H),5.84(dd,J=15.6,1.4Hz,1H),5.74( dt,J=5.9,3.0Hz,1H),5.63–5.51(m,1H),5.45–5.30(m,1H),4.19(d,J=5.7Hz,1H),4.16( d,J=11.2Hz,1H),3.98(s,1H),3.92(d,J=9.9Hz,1H),3.88(t,J=7.1Hz,1H),3.78(tt,J=8 .6,3.7Hz,1H),3.61(d,J=9.5Hz,1H),3.55–3.44(m,1H),3.44-3.40(m,2H),3.24(dd,J=8 .2,5.8Hz,1H),3.19(s,1H),3.02(dd,J=8.2,5.9Hz,1H),2.90(s,1H),2.65(q,J=7.2Hz,1 H),2.52(q,J=6.8Hz,1H),2.41-2.26(m,3H),2.15-19.3(m,8H),1.89–1.80(m,23H),1.19 -1.17(m,9H),1.12(d,J=6.9Hz,3H),1.11(d,J=6.9Hz,3H),1.09(d,J=6.9Hz,3H),1.03(d , J=6.6Hz, 3H), 0.87 (d, J=7.0Hz, 3H), 0.83 (d, J=6.9Hz, 3H), 0.74 (t, J=7.4Hz, 3H) (Figure 59).

[0211] NMR carbon spectrum test: 13 C NMR (101MHz, CDCl3) δ177.30,176.45,165.14,147.88,132.11,130.70,120.77,96.89,81.98 ,72.74,70.66,70.45,70.25,69.41,66.29,62.67,50.73,47.51,44.40,41.01,40.73,40.03, 39.30,37.30,35.64,34.48,33.37,32.43,32.25,29.81,28.81,28.68,27.88,27.77,25.65,25.15,24.83,24.05,21.22,19.88,14.31,13.67,13.61,10.08,9.41,7.97,7.79,3.64 (Figure 60).

[0212] Example 21 Synthesis of Compound RTM-W-XZW-0656

[0213] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add benzenesulfonyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0214] RTM-W-XZW-0656 synthetic route

[0215] Mass spectrometry test: RTM-W-XZW-0656 molecular formula C 50 H 76 O 13 S, molecular weight 916 (Figure 61).

[0216] Nuclear magnetic hydrogen spectrum test: 1 H NMR (400MHz, CDCl3) δ7.82–7.75(m,2H),7.57(dd,J=7.5,7.5Hz,1H),7.46(dd,J=7.7,7.5Hz,2H),6.79(dd,J=15.7,9.5Hz,1H),6.05–5.83(m,2H ),5.80(d,J=15.7Hz,1H),5.52–5.36(m,1H),5.29–5.15(m,3H),4.02-3. 94(m,2H),3.91–3.84(m,1H),3.81(d,J=0.9Hz,1H),3.80–3.73(m,1H),2 .88(q,J=7.3Hz,1H),2.71(qd,J=6.9,1.6Hz,1H),2.3-0.80(m,26),1.18 (d,J=6.7Hz,3H),1.13(d,J=6.9Hz,3H),1.05(s,3H),0.97(d,J=6.9Hz,3 H), 0.95 (d, J = 6.9Hz, 3H), 0.92 (d, J = 5.9Hz, 3H), 0.88 (d, J = 7.0Hz, 3H), 0.85 (d, J = 4.1Hz, 3H), 0.82 (d, J = 6.7Hz, 3H), 0.77 (6, J = 6.7Hz, 3H) (Figure 62).

[0217] NMR carbon spectrum test: 13C NMR (101MHz, CDCl3) δ215.01,164.27,148.09,137.33,135.94,132.80,131.56,129.08,128.16 ,128.03,126.77,126.53,121.54,96.50,82.07,81.79,72.01,71.55,69.85,69.07,66.38,63. 64,44.68,44.22,43.97,41.58,40.17,39.12,37.53,34.49,34.20,32.51,30.35,29.64,29.52,28.87,27.21,25.55,23.74,19.99,17.15,13.81,13.50,11.15,10.27,7.91,7.60,4.29 (Figure 63).

[0218] Example 22 Synthesis of Compound RTM-W-XZW-0657

[0219] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add p-toluenesulfonyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0220] RTM-W-XZW-0657 Synthesis Route

[0221] Mass spectrometry test: RTM-W-XZW-0657 molecular formula C 51 H 78 O 13 S, molecular weight 930 (Figure 64).

[0222] Nuclear magnetic hydrogen spectrum test: 1H NMR (400MHz, CDCl3) δ7.67(d,J=8.0Hz,2H),7.25(d,J=8.0Hz,2H),6.80(dd,J=15.7,9.5Hz,1H),6.00–5.85(m,2H),5.80(d ,J=15.7Hz,1H),5.46–5.39(m,1H),5.28–5.19(m,3H),4.00–3.75(m,6H),2.89–2.85(m,1H),2.72–2.67(m,1H),2.36(s,3H) ),2.33–0.80(m,27H),1.18(d,J=6.6Hz,3H),1.13(d,J=6.6Hz,3H),1.06(s,3H),0.96(d,J=6.6Hz,3H),0.95(d,J=6.6Hz,3 H), 0.93 (d, J = 6.6 Hz, 3H), 0.88 (d, J = 6.6 Hz, 3H), 0.86 (d, J = 6.6 Hz, 3H), 0.81 (d, J = 6.6 Hz, 3H), 0.76 (T, J = 6.6 Hz, 3H) (Figure 65).

[0223] NMR carbon spectrum test: 13 C NMR (101MHz, CDCl3) δ214.98,164.29,148.12,143.82,137.31,132.99,131.55,129.09,128.63 ,128.03,126.80,121.52,96.50,82.07,81.50,72.01,71.55,69.85,69.08,66.38,63.63,44.6 9,44.22,43.93,41.57,40.19,39.12,37.54,34.48,34.20,32.51,30.36,29.64,29.53,28.86,27.22,25.55,23.74,20.66,20.00,17.14,13.86,13.51,11.15,10.27,7.92,7.61,4.28 (Figure 66).

[0224] Example 23 Synthesis of Compound RTM-W-XZW-0677

[0225] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) in dichloromethane (5.0 mL), add p-tert-butylbenzenesulfonyl chloride (0.1 mmol, 1.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0226] RTM-W-XZW-0677 synthesis route mass spectrometry test: RTM-W-XZW-0677 molecular formula C 54 H 84 O 13 S, molecular weight 972 (Figure 67).

[0227] H NMR test: 1H NMR (400MHz, CDCl3) δ7.73–7.70 (m, 2H), 7.49–7.43 (m, 2H), 6.79 (dd, J=15.9, 9.4, Hz, 1H), 6.03–5.72 (m, 3H), 5.49–5.37 (m, 1H), 5.24–5.18 (m, 2H), 4.08–3.80 (m, 6H), 2.78-2.69 (m, 1H), 2.76-2.72 (m, 1H), 2.25-0.80 (m, 28H), 1.27 (s,9H),1.18(d,J=6.6Hz,3H),1.12(d,J=6.5Hz,3H),1.06(s,3H),0.97(d,J=6.5Hz,3H),0.95(d,J=6.5Hz,3H),0.9 4(d,J=6.5Hz,3H),0.92(d,J=6.5Hz,3H).0.86(d,J=6.5Hz,3H),0.84(d,J=6.5Hz,3H),0.77(t,J=7.3Hz,3H) (Figure 68).

[0228] Nuclear magnetic resonance carbon spectrum test: 13C NMR (101MHz, CDCl3) δ215.05, 164.29, 156.81, 148.11, 137.36, 132.79, 131.57, 129.06, 128.01, 126.72, 126.69, 125.01, 124.98, 121.52, 96.51, 82.09, 81.22, 72.01, 71.53, 69.87, 69.08, 66.37, 63.65, 44. 66,44.21,43.87,41.55,40.22,39.13,37.56,34.44,34.27,34.18,32.50,30.37,30.09,30.00,29.64,29.50,28.88,27.19,25.55,23.72,19.99,17.14,13.91,13.51,11.14,10.27,7.94,7.60,4.28 (Figure 69).

[0229] Example 24 Synthesis of Compound RTM-LHY-0368

[0230] Synthesis method: Oligomycin D (200 mg, 0.26 mmol, 1.00 eq.) and N,N-dimethylaminopyridine (190.59 mg, 1.56 mmol, 6.00 eq.) were dissolved in dichloromethane (5 mL). Stirred at 0°C for 30 min, monomethyl oxalyl chloride (191.12 mg, 1.56 mmol, 6.00 eq.) was slowly added dropwise, and the mixture was allowed to react at room temperature for 6 h. After completion of the reaction, the solvent was removed under reduced pressure by TLC monitoring. Column chromatography yielded 90.00 mg of the product (white solid, 45% yield).

[0231] RTM-LHY-0368 Synthesis Route

[0232] Mass spectrometry test: RTM-LHY-0368 molecular formula C 50 H 76 O 17 , molecular weight 948 (Figure 70).

[0233] Nuclear magnetic hydrogen spectrum test: 1H NMR(400MHz, CDCl3) δ6.77(dd,J=15.7,9.4Hz,1H),6.14(dd,J=14.9,10.5Hz,1H),6.00–5.86(m,2H),5.54(dd,J=6.4,2.2Hz, 1H),5.47–5.29(m,4H),5.24(s,1H),5.23–5.13(m,2H),4.37-4.29(m,9H),3.97–3.82(m,1H),3.83–3.72(m,1H),3.64-3.59(m ,1H),3.27(s,1H),3.11–2.92(m,2H),2.79-2.71(m,1H),2.20–0.80(m,31H),1.31(s,3H),1.16(d,J=7.1Hz,3H),1.10(d,J=6 .7Hz, 3H), 1.03 (d, J = 7.0Hz, 6H), 0.99 (d, J = 7.0Hz, 3H), 0.94 (d, J = 7.0Hz, 3H), 0.91 (d, J = 6.9Hz, 3H), 0.87–0.79 (m, 6H) (Figure 71).

[0234] NMR carbon spectrum test: 13 C NMR (101MHz, CDCl3) δ215.59,209.61,164.62,157.98,157.75,157.64,157.54,157.40,157.08,156.67,156.5 0,146.92,137.77,133.87,130.50,128.61,124.08,97.34,83.02,80.61,76.78,72.76,70.79,69.64,67.81,63 .36,63.28,63.15,63.02,45.32,43.97,43.59,40.95,39.55,39.19,35.64,35.27,33.20,31.03,30.09,29.97,29.61,28.14,26.29,22.47,20.70,16.70,16.18,13.92,13.89,12.91,11.88,11.10,10.78,9.58,5.24 (Figure 72).

[0235] Example 25 Synthesis of Compound RTM-XZW-0302

[0236] Synthesis method: Dissolve rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.1 mmol, 1.0 eq.) in dichloromethane (5.0 mL), add ethylsulfonyl chloride (0.2 mmol, 2.0 eq.), and react at room temperature for 4 h. After completion of the reaction, extract with water and ethyl acetate. The organic layer is washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The crude product is purified by silica gel column chromatography to obtain a white solid.

[0237] RTM-XZW-0302 Synthesis Route

[0238] Mass spectrometry test: RTM-XZW-0302 molecular formula C 48 H 80 O 15 S2, molecular weight 960 (Figure 73).

[0239] Nuclear magnetic hydrogen spectrum test: 1 H NMR (400MHz, CDCl3) δ6.70 (dd, J=15.7, 9.5Hz, 1H), 6.01–5.83 (m, 3H), 5.76 (d, J=15.7Hz, 1H), 5.47-5.4 0(m,1H),5.28–5.09(m,4H),4.84–4.80(m,1H),3.89–3.44(m,7H),3.09–3.04(m,6H),2.82–2.76(m,1H), 2.72–2.67(m,1H),2.29–0.80(m,18H),1.42(d,J=6.2Hz,3H),1.37-1.34(m,9H),1.11(d,J=6.6Hz,6H),1 .08 (s, 3H), 1.02 (d, J = 6.9Hz, 3H), 0.95 (d, J = 6.7Hz, 3H), 0.86 (d, J = 7.0Hz, 3H), 0.80–0.74 (m, 6H) (Figure 74).

[0240] Nuclear magnetic carbon spectrum test: 13C NMR (101MHz, CDCl3) δ 216.08, 164.21, 147.77, 137.40, 131.67, 129.03, 127.89, 121.61, 96.61, 82.12, 80.22, 72.03, 71.67, 69.77, 69.17, 67.21, 45.51, 45.34, 44.23, 44.19, 44.13 ,40.03,39.88,39.09,37.57,34.36,33.87,32.53,30.27,28.96,28.69,28.62,26.77,25.19,21.12,20.03,17.10,14.04,13.50,11.19,10.04,7.76,7.47,7.23,7.10,3.99 (Figure 75).

[0241] Example 26 Synthesis of Compound RTM-0211

[0242] To synthesize compound RTM-0211, the raw material RTM was dissolved in tetrahydrofuran, and p-nitrobenzoic acid, triphenylphosphine, and ethyl azodicarboxylate were added to react. After the first step, the resulting product was dissolved in a tetrahydrofuran and methanol solution, and potassium carbonate was added for hydrolysis to obtain the target product RTM-0211. The configuration of the hydroxyl groups at positions 5, 9, 12, 13, and 33 of RTM was reversed to obtain the target compound RTM-0211 in a yield of 53%. The nuclear magnetic resonance (NMR) spectrum of RTM-A-24 revealed that its structure was different from RTM, with a significant difference in the proton peak chemical shift between 1.0 and 3.0. High-resolution mass spectrometry revealed that the m / z of RTM-0211 was 776.5075, consistent with that of RTM, indicating that RTM-0211 is the product of the reversed configuration of the hydroxyl groups of RTM.

[0243] RTM-0211 synthetic route

[0244] Example 27 Synthesis of Compound RTM-0212

[0245] To synthesize compound RTM-0212, the raw material RTM was dissolved in ethanol, and hydrochloric acid and hydrazine were added. The carbonyl group at position 7 of RTM then reacted to form an oxime, yielding the target compound RTM-0212. A proton nuclear magnetic resonance (NMR) spectrum of RTM-0212 revealed a distinct structure from RTM, with hydrogen chemical shifts between 1.0 and 3.0 distinct. Mass spectrometry revealed a molecular weight of 790 for RTM-0212, confirming the product's structural characteristics are consistent with those of RTM-0212.

[0246] Example 28 Test on the inhibition rate of RTM and its derivatives against wheat scab

[0247] The inhibitory rate of 20 mg / L RTM and its derivatives against wheat fusarium sphaeroides was determined using the pathogen mycelium growth method (Table 1).

[0248] Table 1 Inhibition rate of 20 mg / L RTM derivatives on wheat fusarium

[0249] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A compound as shown in the following formula I or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof:

2. The compound according to claim 1 or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, characterized in that: R1 is selected from -OH, -N3, -OC(=O)-benzene ring-(C0~C3 alkyl), -OS(=O)(=O)-benzene ring-Cl, -OC(=O)-benzene ring-O-(C0~C3 alkyl), -OC(=O)-benzene ring-benzene ring, -OC(=O)-benzene ring-N(CH3)(CH3), -OC(=O)-C(=O)-O-(C0~C3 alkyl), -OC(=O)-benzene ring-CF3, -OC(=O)-benzene ring-CCl3, -OC(=O)-(C0~C3 alkyl)-benzene ring, -OC(=O)-CH=CH-benzene ring, -OC(=O)-benzene ring-NO2, -OC(=O)-(C0~C3 alkyl), -OS(=O)(=O)-benzene ring-(C0-C4 alkyl), -OS(=O)(=O)-(C0~C3 alkyl).

3. The compound according to claim 1 or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, characterized in that: R2 and R3 are selected from H, and a double bond is formed between the C to which R2 is connected and the C to which R3 is connected.

4. The compound according to claim 1 or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, characterized in that: R4 is selected from -OH, -OC(=O)-benzene ring-(C0~C3 alkyl), -OC(=O)-benzene ring-benzene ring, -OC(=O)-C(=O)-O-(C0~C3 alkyl), -OC(=O)-benzene ring-CF3, -OC(=O)-benzene ring-CCl3, N3, -OC(=O)-C(=O)-O-(C0~C3 alkyl), -OS(=O)(=O)-(C0~C3 alkyl).

5. The compound according to claim 1 or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, characterized in that: R5 is selected from =O or =N-NH2.

6. The compound according to claim 1 or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, characterized in that: R6 is selected from -OH, -N3, -OC(=O)-phenyl ring-(C0~C3 alkyl), -OC(=O)-C(=O)-O-(C0~C3 alkyl).

7. The compound according to claim 1 or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, characterized in that: R7 is selected from -OH, -OC(=O)-C(=O)-O-(C0~C3 alkyl).

8. The compound according to claim 1 or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, characterized in that: R8, R9, R 10 With R 11 is selected from H, the C to which R8 is connected forms a double bond with the C to which R9 is connected, and R 10 Connected C and R 11 The C connected to R8 forms a double bond; or the C connected to R9 is connected to R8 through O to form a three-membered cyclic ether, R 10 Connected C and R 11 The connected C forms a double bond; or the C connected to R9 and R 10 The connected C forms a double bond, and the C connected to R8 forms a double bond with R 11 The connected C connection; or R9 connected to C and R 10 The connected C forms a double bond, and the C connected to R8 forms a double bond with R 11 The connected C connection; or R9 connected to C and R 10 The connected C forms a double bond, and the C connected to R8 forms a double bond with R 11 The connected C connection; or R9 connected to C and R 10 The connected C forms a double bond, and the C connected to R8 forms a double bond with R 11 The connected C connect.

9. The compound according to any one of claims 1 to 8 or a pharmaceutically acceptable salt, isotopic variant, tautomer, stereoisomer, prodrug, polymorph, hydrate or solvate thereof, which can be used for preventing and controlling wheat fusarium head blight in the agricultural field, characterized in that: The structural formula of the compound used to prevent and treat wheat scab is selected from one of the following:

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