Rustaveline derivatives and uses thereof

Abstract

Based on the structure of rutamycin, this invention provides structural derivation and a series of new compounds with certain physiological activities that have a good inhibitory effect on wheat scab.

Description

Technical Field

[0001] The priority information for this invention is as follows: priority number 2023116800133, priority date December 8, 2023, invention title: Rustatin Derivatives and Their Uses, the disclosure of which is incorporated herein by reference. This invention relates to the field of compounds, specifically to rustatin derivatives and their uses. Background Technology

[0002] Rutamycin (hereinafter abbreviated as RTM), also known as oligomycin D, is a class of macrolide antibiotics produced by Streptomyces p., and its structural formula is as follows:

[0003] Summary of the Invention

[0004] Based on the structure of rutamycin, this invention provides structural derivation on its basis and offers a series of new compounds with certain physiological activities.

[0005] Specifically, compounds of Formula I or their pharmaceutically acceptable salts, isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates, or solvates:

[0006]

[0007] 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).

[0008] R2 and R3 are selected from H, and a double bond is formed between the C bond connected to R2 and the C bond connected to R3.

[0009] 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), and -OS(=O)(=O)-(C0~C3 alkyl).

[0010] R5 is selected from =O or =N-NH2.

[0011] R6 is selected from -OH, -N3, -OC(=O)-benzene ring-(C0~C3 alkyl), -OC(=O)-C(=O)-O-(C0~C3 alkyl).

[0012] R7 is selected from -OH, -OC(=O)-C(=O)-O-(C0~C3 alkyl);

[0013] R8, R9, R 10 With R 11 Selected from H, the C bond connected to R8 and the C bond connected to R9 form a double bond, R 10 Connected C and R 11 The connected carbons form a double bond; or the carbons connected to R8 and R9 are connected by an oxygen atom to form a three-membered ring ether. 10 Connected C and R 11 Connected Cs form a double bond; or R9 connects C and R 10 The connected C atoms form a double bond, and the R8 bonds connect the C atoms to the R atoms. 11 The connected C passes through Connect; or connect C and R9. 10 The connected C atoms form a double bond, and the R8 bonds connect the C atoms to the R atoms. 11 The connected C passes through Connect; or connect C and R9. 10 The connected C atoms form a double bond, and the R8 bonds connect the C atoms to the R atoms. 11 The connected C passes through Connect; or connect C and R9. 10 The connected C atoms form a double bond, and the R8 bonds connect the C atoms to the R atoms. 11 The connected C passes through connect.

[0014] Furthermore, the above structure does not include rutamycin.

[0015] This application also provides the use of the above-mentioned compounds or their pharmaceutically acceptable salts, isotopic variants, tautomers, stereoisomers, prodrugs, polymorphs, hydrates or solvates in the control of wheat scab.

[0016] To more clearly describe the content of this application, the terms used are defined as follows:

[0017] In this application, C1 to Cn includes C1 to C2, C1 to C3...C1 to Cn, where n is an integer greater than one. Prefixes used as substituents indicate the minimum and maximum number of carbon atoms in the substituent. For example, "C1 to C6 alkyl" refers to a straight-chain or branched alkyl group containing one to six carbon atoms. In this application, "C0 alkyl" indicates that there is no group present.

[0018] The beneficial effects of this invention are: based on the structure of rutamycin, this invention conducts structural derivation on its basis and provides a series of new compounds with certain physiological activities, which have a good inhibitory effect on wheat scab. Attached Figure Description

[0019] Figure 1 This is the mass spectrometry characteristic map of Example 1;

[0020] Figure 2 The hydrogen NMR spectrum of Example 1;

[0021] Figure 3 The carbon NMR spectrum of Example 1;

[0022] Figure 4 This is the mass spectrometry characteristic map of Example 2;

[0023] Figure 5 The hydrogen NMR spectrum of Example 2;

[0024] Figure 6 The carbon NMR spectrum of Example 2;

[0025] Figure 7 This is the mass spectrometry characteristic map of Example 3;

[0026] Figure 8 The hydrogen NMR spectrum of Example 3;

[0027] Figure 9 The carbon NMR spectrum of Example 3;

[0028] Figure 10 This is the mass spectrometry characteristic map of Example 4;

[0029] Figure 11 The hydrogen NMR spectrum of Example 4;

[0030] Figure 12 The carbon NMR spectrum of Example 4;

[0031] Figure 13 The mass spectrometry characteristic map of Example 5;

[0032] Figure 14 The hydrogen NMR spectrum of Example 5;

[0033] Figure 15 The carbon NMR spectrum of Example 5;

[0034] Figure 16 The mass spectrometry characteristic map of Example 6;

[0035] Figure 17 The hydrogen NMR spectrum of Example 6;

[0036] Figure 18 The carbon NMR spectrum of Example 6;

[0037] Figure 19 The mass spectrometry characteristic map of Example 7;

[0038] Figure 20 The hydrogen NMR spectrum of Example 7;

[0039] Figure 21 The carbon NMR spectrum of Example 7;

[0040] Figure 22 The mass spectrometry characteristic map of Example 8;

[0041] Figure 23 The 1H NMR spectrum of Example 8;

[0042] Figure 24 The carbon NMR spectrum of Example 8;

[0043] Figure 25 The mass spectrometry characteristic map of Example 9;

[0044] Figure 26 The hydrogen NMR spectrum of Example 9;

[0045] Figure 27 The carbon NMR spectrum of Example 9;

[0046] Figure 28 The mass spectrometry characteristic map of Example 10;

[0047] Figure 29 The hydrogen NMR spectrum of Example 10;

[0048] Figure 30 The carbon NMR spectrum of Example 10;

[0049] Figure 31 The mass spectrometry characteristic map of Example 11;

[0050] Figure 32 The hydrogen NMR spectrum of Example 11;

[0051] Figure 33 The carbon NMR spectrum of Example 11;

[0052] Figure 34 The mass spectrometry characteristic map of Example 12;

[0053] Figure 35 The hydrogen NMR spectrum of Example 12;

[0054] Figure 36 The carbon NMR spectrum of Example 12;

[0055] Figure 37 The mass spectrometry characteristic map of Example 13;

[0056] Figure 38 The hydrogen NMR spectrum of Example 13;

[0057] Figure 39 The carbon NMR spectrum of Example 13;

[0058] Figure 40 The mass spectrometry characteristic map of Example 14;

[0059] Figure 41 The hydrogen NMR spectrum of Example 14;

[0060] Figure 42 The carbon NMR spectrum of Example 14;

[0061] Figure 43 The mass spectrometry characteristic map of Example 15;

[0062] Figure 44 The hydrogen NMR spectrum of Example 15;

[0063] Figure 45 The carbon NMR spectrum of Example 15;

[0064] Figure 46 The mass spectrometry characteristic map of Example 16;

[0065] Figure 47 The hydrogen NMR spectrum of Example 16;

[0066] Figure 48 The carbon NMR spectrum of Example 16;

[0067] Figure 49 The mass spectrometry characteristic map of Example 17;

[0068] Figure 50 The hydrogen NMR spectrum of Example 17;

[0069] Figure 51 The carbon NMR spectrum of Example 17;

[0070] Figure 52 The mass spectrometry characteristic map of Example 18;

[0071] Figure 53 The hydrogen NMR spectrum of Example 18;

[0072] Figure 54 The carbon NMR spectrum of Example 18;

[0073] Figure 55 The mass spectrometry characteristic map of Example 19;

[0074] Figure 56 The hydrogen NMR spectrum of Example 19;

[0075] Figure 57 The carbon NMR spectrum of Example 19;

[0076] Figure 58 The mass spectrometry characteristic map of Example 20;

[0077] Figure 59 The hydrogen NMR spectrum of Example 20;

[0078] Figure 60 The carbon NMR spectrum of Example 20;

[0079] Figure 61 The mass spectrometry characteristic map of Example 21;

[0080] Figure 62 The hydrogen NMR spectrum of Example 21;

[0081] Figure 63 The carbon NMR spectrum of Example 21;

[0082] Figure 64 The mass spectrometry characteristic map of Example 22;

[0083] Figure 65 The hydrogen NMR spectrum of Example 22;

[0084] Figure 66 The carbon NMR spectrum of Example 22;

[0085] Figure 67 The mass spectrometry characteristic map of Example 23;

[0086] Figure 68 The hydrogen NMR spectrum of Example 23;

[0087] Figure 69 The carbon NMR spectrum of Example 23;

[0088] Figure 70 The mass spectrometry characteristic map of Example 24;

[0089] Figure 71 The hydrogen NMR spectrum of Example 24;

[0090] Figure 72 The carbon NMR spectrum of Example 24;

[0091] Figure 73 The mass spectrometry characteristic map of Example 25;

[0092] Figure 74 The hydrogen NMR spectrum of Example 25;

[0093] Figure 75 This is the carbon NMR spectrum of Example 25. Detailed Implementation

[0094] Example 1: Synthesis of compound RTM-0215

[0095] Synthetic method: Rutamycin (400.0 mg, 0.515 mmol, 1.0 eq.) was dissolved in dichloromethane (10 mL) and activated at 0 °C for 20 min. Benzoyl chloride (0.359 mL, 3.09 mmol, 6.0 eq.) was added, and the reaction was carried out at 25 °C for 4 h. After the reaction was completed, the pH was adjusted to acidic with 2NH4Cl, and the mixture was extracted with water and dichloromethane (3 x 15 mL). The organic layer was 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 was purified by silica gel column chromatography (dichloromethane / methanol = 100 / 1) to give 374.4 mg (white solid), yield 41.6%.

[0096]

[0097] RTM-0215 ​​Synthesis Route

[0098] Mass spectrometry test: RTM-0215 ​​molecular formula C 58 H 80 O 13 Molecular weight 983 Figure 1 ).

[0099] 1H NMR spectroscopy: 1HNMR(400MHz, CDCl3) δ 8.01–7.87 (m, 4H), 7.54–7.44 (m, 2H), 7.37 (q, J=7.7Hz, 4H), 6.84 (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 ).

[0100] 13C NMR test: 13 C NMR(101MHz, CDCl3) δ 216.57, 165.00, 164.72, 164.11, 147.69, 137.10, 132.27, 131.70, 131.49, 129.90, 129.20, 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 ).

[0101] Example 2: Synthesis of compound RTM-XZW-0304

[0102] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and o-chlorobenzenesulfonyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0103]

[0104] Mass spectrometry analysis of the RTM-XZW-0304 synthesis route: RTM-XZW-0304 molecular formula C 50 H 75 O 13 ClS, molecular weight 951 ( Figure 4 ).

[0105] 1H NMR spectroscopy: 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=15.9,9.4H z,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 .70–2.63(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 ).

[0106] Carbon NMR spectroscopy test: 13C NMR (101MHz, CDCl3) δ214.55,164.17,147.92,137.28,134.70,133.45,131.84,131.51,130.98,129. 22,129.04,127.96,125.81,121.57,96.43,84.18,82.04,71.91,71.55,69.83,69.03,66.34,63.62, 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 ).

[0107] Example 3 Synthesis of compound RTM-m-CPBA

[0108] Synthesis method: Rutamycin (200 mg, 0.13 mmol, 1.00 eq.) and m-chloroperoxybenzoic acid (67.30 mg, 67.30 mmol, 1.50 eq.) were weighed and dissolved in dichloromethane (5 mL). The reaction was carried out at -17 °C for 6 h. After the reaction was completed by TLC monitoring, 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 was removed under reduced pressure. Column chromatography yielded a white powder.

[0109]

[0110] RTM-m-CPBA Synthesis Route

[0111] Mass spectrometry test: RTM-m-CPBA molecular formula C 44 H 72 O 12 Molecular weight 792 Figure 7 ).

[0112] 1H NMR spectroscopy: 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=10.1 Hz,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 .73–1.09(m,10H),1.27(d,J=7.3Hz,3H),1.18(d,J=7.3Hz,3H),1.12(d,J=7.3 Hz,3H),1.06(s,3H),1.01(d,J=6.4Hz,3H),1.00(d,J=6.4Hz,3H),0.98(d,J=6 .4Hz,3H),0.86(d,J=6.4Hz,3H),0.83(d,J=6.4Hz,3H),0.71(t,J=7.4Hz,3H)( Figure 8 ).

[0113] Carbon NMR spectroscopy test: 13 C NMR (101MHz, CDCl3) δ163.81,148.22,138.48,124.95,121.73,96.39,81.95,8 0.57,72.51,72.18,71.75,69.40,68.75,66.54,63.76,45.16,45.03,42.48,41 .47,40.71,38.92,34.66,33.78,33.37,29.66,28.81,28.56,27.24,26.39,26.27,25.50,23.70,19.20,16.46,16.08,13.06,10.62,10.37,7.62,7.25,4.84( Figure 9 ).

[0114] Example 4: Synthesis of compound RTM-317

[0115] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and m-methoxybenzoyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0116]

[0117] RTM-317 Synthesis Route

[0118] Mass spectrometry test: RTM-317 molecular formula C 52 H 78 O 13 Molecular weight 910 Figure 10 ).

[0119] 1H NMR spectroscopy: 1 HNMR (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=15.7,9.8H z,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)( Figure 11 ).

[0120] Carbon NMR spectroscopy test: 13C NMR (101MHz, CDCl3) δ217.46,165.62,165.25,159.64,149.01,138.22,132.50,130.88,130.13,129. 56,129.07,122.60,122.05,119.35,114.62,97.50,83.20,74.30,73.31,72.55,70.83,70.17,67.38, 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 ).

[0121] Example 5: Synthesis of compound RTM-XZW-0320

[0122] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.3 mmol, 3.0 eq.) were dissolved in dichloromethane (5.0 mL), and biphenyl-4-formyl chloride (0.2 mmol, 2.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0123]

[0124] RTM-XZW-0320 Synthetic Route Mass Spectrometry Test: RTM-XZW-0320 Molecular Formula C 70 H 88 O 13 Molecular weight 1136 ( Figure 13 ).

[0125] 1H NMR spectroscopy: 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),3.7 8–3.76(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= 7.3Hz,3H),0.91(d,J=7.3Hz,3H),0.81(d,J=7.3Hz,3H),0.55(t,J=7.3Hz,3H)( Figure 14 ).

[0126] Carbon NMR spectroscopy 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 .18,129.15,129.04,128.63,127.93,127.89,127.79,127.19,127.06,126.30,126.23,125.99,121.69,96.40,82.1 3,73.19,72.28,71.53,69.66,69.00,68.42,66.75,44.92,44.16,43.73,39.56,39.48,39.09,37.50,34.44,34.27,32.51,30.66,29.79,29.28,28.69,26.95,25.30,20.20,20.14,17.28,13.58,13.47,11.20,10.21,7.85,7.61,4.19( Figure 15 ).

[0127] Example 6: Synthesis of compound RTM-XZW-0318. Synthesis method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and 4-dimethylaminobenzoyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was complete, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0128]

[0129] Mass spectrometry analysis of the RTM-XZW-0318 synthetic route: RTM-XZW-0318 molecular formula C 53 H 81 O 12 Molecular weight 923 Figure 16 ).

[0130] 1H NMR spectroscopy: 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=1 4.9,10.5Hz,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 ).

[0131] Carbon NMR spectroscopy 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 ).

[0132] Example 7 Synthesis of compound RTM-LHY-0366

[0133] Synthetic 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 weighed and dissolved in dichloromethane (5 mL). The mixture was stirred at 0 °C for 30 min, and oxaloyl chloride monoethyl ester (191.12 mg, 1.56 mmol, 6.00 eq.) was slowly added dropwise. The mixture was then transferred to room temperature and reacted for 6 h. After the reaction was completed by TLC monitoring, the solvent was removed under reduced pressure. Column chromatography yielded 90.00 mg of product (white solid, yield 45%).

[0134]

[0135] Mass spectrometry analysis of the RTM-LHY-0366 synthesis route: RTM-LHY-0366 molecular formula C 52 H 80 O 17 Molecular weight 976 Figure 19 ).

[0136] 1H NMR spectroscopy: 1H NMR (400MHz, Chloroform-d) δ 6.84–6.65 (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=6.9Hz,3H),1.00(d,J=6.8Hz,3H),0.96–0.93(m,6H),0.87(d,J=6.9Hz,3H),0.75(t,J=5.9Hz,6H)( Figure 20 ). Carbon NMR spectroscopy: 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, 62.0 6,44.77,44.34,43.48,39.26,39.07,38.58,37.46,34.38,34.12,32.51,29.46,29.05,28.63,27.16,25.19,20.01,19.75,17.05,13.57,13.29,12.91,11.19,10.06,7.86,7.45,4.02( Figure 21 ).

[0137] Example 8 Synthesis of compound RTM-XZW-0366-2

[0138] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and o-methylbenzoyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0139]

[0140] Mass spectrometry analysis of the synthetic route of RTM-XZW-0366-2: Molecular formula of RTM-XZW-0366-2 C 52 H 78 O 12 Molecular weight 895 Figure 22 ).

[0141] 1H NMR spectroscopy: 1H NMR (400MHz, DMSO) δ 7.78 (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),2.79–2.6 9(m,1H),2.48(s,2H),2.38(q,J=7.9Hz,1H),2.04–1.90(m,4H),1.76(q,J=6.8,5.9H z,1H),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)( Figure 23 ).

[0142] Carbon NMR spectroscopy: 13C NMR (101 MHz, DMSO) δ 214.24, 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, 7 0.44,68.92,67.56,63.08,45.40,45.25,44.91,42.97,41.43,38.59,35.56,33.88,33.85,30.83,30.62,30.30,29.70,28.59,26.62,25.36,24.37,22.58,21.40,17.77,15.50,14.43,12.42,11.63,9.65,9.49,5.72( Figure 24 ).

[0143] Example 9: Synthesis of compound RTM-XZW-0401-1

[0144] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.3 mmol, 3.0 eq.) were dissolved in dichloromethane (5.0 mL), and o-trifluoromethylbenzoyl chloride (0.2 mmol, 2.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0145]

[0146] Mass spectrometry analysis of the synthetic route of RTM-XZW-0401-1: Molecular formula of RTM-XZW-0401-1 is C60H78O13F6, molecular weight is 1120 (…). Figure 25 ). 1H NMR spectroscopy test: 11H NMR (400 MHz, CDCl3) δ 7.86 (dd, J = 7.2, 2.0 Hz, 1H), 7.81 (dd, J = 7.3, 1.8 Hz, 1H), 7.75 (dd, J = 7.3, 1.9 Hz, 2H), 7.63 - 7.51 (m, 4H), 6.89 (dd, J = 15.7, 9.6 Hz, 1H), 6.07 – 5.82 (m, 3H), 5.69 (dd, J = 10.5, 2.1 Hz, 1H), 5.55 – 5.43 (m, 1H), 5.28 – 5.16 (m, 3H), 3.96 - 3.88 (m, 1H), 3.93 (d, J = 1.6 Hz, 1H), 3.86 3.76 (m, 1H), 3.74 – 3.67 (m, 2H), 3.29 (s, 1H), 3.00 (q, J = 7.3 Hz, 1H), 2.87 (qd, J = 6.9, 2.2 Hz, 1H), 2.29 – 0.08 (m, 23H), 1.35 (d, J = 6.9 Hz, 3H), 1.10 (s, 3H), 1.07 (d, J = 6.9 Hz, 3H), 1.05 (d, J = 6.9 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H), 0.97 (d, J = 6.9 Hz, 3H), 0.93 (d, J = 6.9 Hz, 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 ).

[0147] 13C NMR test: 13 13C NMR (101 MHz, CDCl3) δ 216.91, 165.06, 164.46, 164.12, 147.86, 137.25, 131.51, 130.91, 130.71, 130.30, 130.10, 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, 69.69, 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 ).

[0148] Example 10 Synthesis of compound RTM-XZW-0415

[0149] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and m-methoxybenzoyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0150]

[0151] Mass spectrometry analysis of the RTM-XZW-0415 synthesis route: RTM-XZW-0415 molecular formula C 53 H 78 O 12 The molecular weight is 908 ( Figure 28 ).

[0152] 1H NMR spectroscopy: 1 HNMR (400MHz, CDCl3) δ7.23-7.19(m,2H),7.15-7.10(m,3H),6.75(dd,J=15.7,9. 8Hz,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), 4.05–3.97(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,1 H),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) ,1.75–1.10(m,16H),1.17(d,J=6.2Hz,3H),1.10(d,J=6.6Hz,3H),1.07(s,3H),0 .96(d,J=6.8Hz,3H),0.94-0.90(m,6H),0.86(d,J=7.0Hz,3H),0.79-0.74(m,9H)( Figure 29 ).

[0153] Carbon NMR spectroscopy test: 13 C NMR (101MHz, CDCl3) δ217.35,172.17,165.18,148.93,140.23,138.21,132.48,130.11,129.04 ,128.48,128.22,126.30,122.55,97.46,83.11,73.52,73.25,72.54,70.78,70.15,67.39,64.6 3,45.99,45.02,44.87,42.67,40.46,40.22,38.52,35.49,35.36,33.56,31.44,30.87,30.72,30.66,29.87,28.38,26.55,24.77,21.08,18.29,14.55,14.18,12.12,11.26,8.70,8.47,5.10( Figure 30 ).

[0154] Example 11 Synthesis of compound RTM-XZW-0419

[0155] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and m-methoxybenzoyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0156]

[0157] Mass spectrometry analysis of the RTM-XZW-0419 synthetic route: RTM-XZW-0419 molecular formula C 53 H 78 O 12 Molecular weight 906 Figure 31 ).

[0158] 1H NMR spectroscopy: 1H NMR(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 .0Hz,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,1 H),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,3 H),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 ).

[0159] Carbon NMR spectroscopy test: 13 C NMR (101MHz, CDCl3) δ216.65,165.07,164.21,148.00,144.69,137.24,133.18,131.48,129.52,1 29.10,128.05,127.89,127.23,121.58,116.24,96.48,82.16,72.71,72.28,71.56,69.79,69.17, 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 ).

[0160] Example 12 Synthesis of compound RTM-LHY-0328

[0161] Synthetic 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 weighed and dissolved in tetrahydrofuran (5 mL). The mixture was stirred at 0 °C for 30 min under argon protection. Diisopropyl azodicarbonate (315.43 mg, 1.56 mmol, 6.00 eq.) was slowly added dropwise, and the mixture was then allowed to react at room temperature for 6 h. After the reaction was complete, the solvent was removed under reduced pressure by TLC. Column chromatography yielded a white powder.

[0162]

[0163] Mass spectrometry analysis of the RTM-LHY-0328 synthesis route: RTM-LHY-0328 molecular formula C 51 H 75 NO 14 Molecular weight 925 Figure 34 ).

[0164] 1H NMR spectroscopy: 11H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.9 Hz, 2H), 8.27–8.19 (m, 2H), 6.63 (dd, J = 15.6, 9.8 Hz, 1H), 6.05 (dd, J = 14.3, 10.8 Hz, 1H), 5.96 (dd, J = 14.7, 10.4 Hz, 1H), 5.82 (d, J = 15.7 Hz, 1H), 5.50 (ddd, J = 14.6, 10.5, 4.0 Hz, 1H), 5.38–5.15 (m, 3H), 4.03–3.92 (m, 2H), 3.84 (t, J = 5.5 Hz, 1H), 3.78 (d, J = 10.1 Hz, 1H), 3.71 (d, J = 8.9 Hz, 1H), 3.67–3.56 (m, 1H), 3.48 (d, J = 1.9 Hz, 1H), 3.35 (s, 1H), 2.81 (dt, J = 9.6, 5.2 Hz, 1H), 2.78–2.72 (m, 1H), 2.53 (d, J = 4.1 Hz, 1H), 2.41 (td, J = 9.8, 6.4 Hz, 1H), 2.22 (d, J = 13.6 Hz, 1H), 2.17–1.86 (m, 5H), 1.63 - 0.9 (m, 15H), 1.45 (d, J = 6.2 Hz, 3H), 1.20 (d, J = 6.5 Hz, 3H), 1.17 (s, 3H), 1.12 (d, J = 6.7 Hz, 3H), 1.11 (d, J = 7.2 Hz, 3H), 1.07 (d, J = 6.9 Hz, 3H), 1.03 (d, J = 6.5 Hz, 3H), 0.97 (d, J = 6.9 Hz, 3H), 0.81 (d, J = 6.9 Hz, 3H), 0.76 (t, J = 7.4 Hz, 3H)( Figure 35 ).

[0165] 13C NMR test: 13C NMR (101 MHz, CDCl3) δ 164.73, 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, 46.78, 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 ).

[0166] Example 13 Synthesis of compound RTM-W-XZW-0474-1

[0167] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and N-phenylmaleimide (1 mmol, 10.0 eq.) were dissolved in toluene (5.0 mL) and reacted at 105 °C for 24 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0168]

[0169] Mass spectrometry analysis of the synthetic route of RTM-W-XZW-0474-1: Molecular formula of RTM-W-XZW-0474-1 C 48 H 75 O 13 N, molecular weight 873 ( Figure 37 ).

[0170] 1H NMR spectroscopy: 1 H NMR (400MHz, CDCl3) δ8.45 (s, 1H), 6.79 (dd, J = 15.6, 6.9Hz, 1H), 5.85-5.8 1(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 .49(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=6.5H z,3H),0.86(d,J=6.9Hz,3H),0.82(d,J=6.9Hz,3H),0.78(t,J=7.4Hz,3H)( Figure 38 ).

[0171] Carbon NMR spectroscopy: 13C NMR (101 MHz, CDCl3) δ 177.44, 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 ).

[0172] Example 14 Synthesis of compound RTM-W-XZW-0511-1

[0173] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and N-phenylmaleimide (1 mmol, 10.0 eq.) were dissolved in toluene (5.0 mL) and reacted at 105 °C for 24 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0174]

[0175] Mass spectrometry analysis of the synthetic route of RTM-W-XZW-0511-1: Molecular formula of RTM-W-XZW-0511-1 C 49 H 77 O 13 N, molecular weight 887 ( Figure 40 ).

[0176] 1H NMR spectroscopy: 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),4.1 7-4.11(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) ,1.16(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 =6.9Hz,3H),0.86(d,J=6.9Hz,3H),0.83(d,J=6.9Hz,3H),0.77(t,J=7.3Hz,3H)( Figure 41 ).

[0177] Carbon NMR spectroscopy test: 13 C NMR (101MHz, CDCl3) δ222.90,220.00,178.18,177.42,166.09,148.91,133.35,131.99,121.9 0,97.86,82.97,73.68,71.62,71.50,71.15,70.61,67.38,63.94,48.39,45.49,42.05,41.81, 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 ).

[0178] Example 15 Synthesis of compound RTM-W-XZW-0526-1

[0179] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and N-benzylmaleimide (1 mmol, 10.0 eq.) were dissolved in toluene (5.0 mL) and reacted at 105 °C for 24 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0180]

[0181] Mass spectrometry analysis of the synthetic route of RTM-W-XZW-0526-1: Molecular formula of RTM-W-XZW-0526-1 C 55 H 81 O 13 N, molecular weight 963 ( Figure 43 ). 1H NMR spectroscopy 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,1 H),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=2.7H z,6H),0.93(d,J=6.5Hz,3H),0.89(d,J=6.6Hz,3H),0.83(t,J=6.9Hz,3H)( Figure 44 Carbon NMR spectroscopy test: 13C NMR (101MHz, CDCl3) δ177.79,177.02,166.03,148.86,135.73,133.37,132.02,128.56,128.21,12 7.74,121.92,97.82,83.00,77.22,73.72,71.55,71.49,71.11,70.61,67.31,63.89,48.38,45.48 ,42.21,42.09,41.76,41.71,40.31,38.50,36.55,35.47,34.45,33.89,33.25,30.76,29.80,29.68,26.65,26.46,25.99,25.04,22.40,20.95,15.57,14.79,14.52,11.11,10.36,9.48,8.78,4.76( Figure 45 ).

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

[0183] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and m-methoxybenzoyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0184]

[0185] Mass spectrometry analysis of the RTM-WC-LHY-0410 synthetic route: RTM-WC-LHY-0410 molecular formula C 44 H 68 N 12 O7, molecular weight 876 Figure 46 ).

[0186] 1H NMR spectroscopy: 1HNMR (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),3.5 5(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 .5Hz,1H),2.35(dd,J=16.0,7.5Hz,1H),2.19–1.90(m,7H),1.85-1.74(m,1H), 1.75–1.29(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)( Figure 47 ).

[0187] 1H NMR spectroscopy: 13 C NMR(101MHz,Chloroform-d)δ164.39,147.74,134.90,130.59,130.00,121.13,96.52,84.86,82.12,72.03,70.24,67.20,53.63,48.91,48.51,44.9 3,42.48,38.40,37.64,37.06,34.52,33.10,32.65,28.81,28.11,27.20, 25.23,19.13,16.87,15.66,12.55,12.42,11.01,10.68,9.89,6.97,3.55( Figure 48 ).

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

[0189] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and benzoyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0190]

[0191] Mass spectrometry analysis of the synthetic route of RTM-W-XZW-0458: Molecular formula of RTM-W-XZW-0458 C 51 H 76 O 12 Molecular weight 880 Figure 49 ).

[0192] 1H NMR spectroscopy: 1 H NMR (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. 23(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 =10.0Hz,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] Carbon NMR spectroscopy: 13C NMR (101 MHz, CDCl3) δ 217.55, 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, 67.3 6,64.62,46.09,45.21,44.76,42.64,40.66,40.61,38.53,35.42,33.57,31.51,30.98,30.65,29.84,28.42,26.52,24.78,21.19,18.37,14.58,14.41,12.15,11.27,8.85,8.59,5.20( Figure 51 ).

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

[0195] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and acetyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid ( Figure 69 ).

[0196]

[0197] Mass spectrometry analysis of the synthetic route of RTM-W-XZW-0539: Molecular formula of RTM-W-XZW-0539 C 46 H 74 O 12 Molecular weight 818 Figure 52 ).

[0198] 1H NMR spectroscopy: 1 H NMR (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, 10.4 Hz,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–

[0199] 4.03(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=1.4 Hz,1H),3.70(d,J=10.1Hz,1H),3.27(s,1H),2.84(q,J=7.5Hz,1H),2.73(qd,J=6.9,2.0H z,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=6.8Hz,3H),1.01(d,J=6.7Hz,3H),1.00(d,J=6.7)( Figure 53 ).

[0200] Carbon NMR spectroscopy 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 ).

[0201] Example 19 Synthesis of compound RTM-W-XZW-0578-2

[0202] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and phenylacetyl chloride (0.2 mmol, 2.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0203]

[0204] Mass spectrometry analysis of the synthetic route of RTM-W-XZW-0578-2: Molecular formula of RTM-W-XZW-0578-2 C 69 H 94 O 13 Molecular weight 1130 ( Figure 55 ).

[0205] 1H NMR spectroscopy: 1 H NMR (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, 1H),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), 2.32–0.80(m,19H),1.20(d,J=6.6Hz,6H),1.06(s,3H),1.03(d,J=6.6H z,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 ).

[0206] Carbon NMR spectroscopy 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 ,129.80,129.25,128.59,128.54,128.35,128.12,127.95,127.80,127.62,127.53,127.37,127.21,126.98,126.22,126.17,126 .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 ).

[0207] Example 20 Synthesis of compound RTM-W-XZW-0621-1

[0208] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and N-cyclohexanemaleimide (1 mmol, 10.0 eq.) were dissolved in toluene (5.0 mL) and reacted at 105 °C for 24 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0209]

[0210] Mass spectrometry analysis of the synthetic route of RTM-W-XZW-0621-1: Molecular formula of RTM-W-XZW-0621-1 C 54 H 85 O 13 N, molecular weight 955 ( Figure 58 ).

[0211] 1H NMR spectroscopy: 11H NMR (400 MHz, CDCl3) δ 6.83 (dd, J = 15.6, 6.2 Hz, 1H), 5.84 (dd, J = 15.6, 1.4 Hz, 1H), 5.74 (dt, J = 5.9, 3.0 Hz, 1H), 5.63–5.51 (m, 1H), 5.45–5.30 (m, 1H), 4.19 (d, J = 5.7 Hz, 1H), 4.16 (d, J = 11.2 Hz, 1H), 3.98 (s, 1H), 3.92 (d, J = 9.9 Hz, 1H), 3.88 (t, J = 7.1 Hz, 1H), 3.78 (tt, J = 8.6, 3.7 Hz, 1H), 3.61 (d, J = 9.5 Hz, 1H), 3.55–3.44 (m, 1H), 3.44 - 3.40 (m, 2H), 3.24 (dd, J = 8.2, 5.8 Hz, 1H), 3.19 (s, 1H), 3.02 (dd, J = 8.2, 5.9 Hz, 1H), 2.90 (s, 1H), 2.65 (q, J = 7.2 Hz, 1H), 2.52 (q, J = 6.8 Hz, 1H), 2.41 - 2.26 (m, 3H), 2.15 - 19.3 (m, 8H), 1.89–1.80 (m, 23H),

[0212] 1.19 - 1.17 (m, 9H), 1.12 (d, J = 6.9 Hz, 3H), 1.11 (d, J = 6.9 Hz, 3H), 1.09 (d, J = 6.9 Hz, 3H), 1.03 (d, J = 6.6 Hz, 3H), 0.87 (d, J = 7.0 Hz, 3H), 0.83 (d, J = 6.9 Hz, 3H), 0.74 (t, J = 7.4 Hz, 3H)( Figure 59 )。

[0213] 13C NMR test: 13 13C NMR (101 MHz, CDCl3) δ 177.30, 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 ).

[0214] Example 21 Synthesis of compound RTM-W-XZW-0656

[0215] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and benzenesulfonyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0216]

[0217] Mass spectrometry analysis of the synthetic route of RTM-W-XZW-0656: Molecular formula of RTM-W-XZW-0656 C 50 H 76 O 13 S, molecular weight 916 ( Figure 61 ).

[0218] 1H NMR spectroscopy: 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–

[0219] 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,1 H),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,2 6),1.18(d,J=6.7Hz,3H),1.13(d,J=6.9Hz,3H),1.05(s,3H),0.97(d,J=6.9Hz,3H),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 ).

[0220] Carbon NMR spectroscopy test: 13 C NMR (101MHz, CDCl3) δ215.01,164.27,148.09,137.33,135.94,132.80,131.56,129.08,128.1 6,128.03,126.77,126.53,121.54,96.50,82.07,81.79,72.01,71.55,69.85,69.07,66.38,6 3.64, 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 ).

[0221] Example 22 Synthesis of compound RTM-W-XZW-0657

[0222] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and p-toluenesulfonyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0223]

[0224] Mass spectrometry analysis of the synthetic route of RTM-W-XZW-0657: Molecular formula of RTM-W-XZW-0657 C 51 H 78 O 13 S, molecular weight 930 ( Figure 64 ).

[0225] 1H NMR spectroscopy: 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=6.6 Hz,3H),0.93(d,J=6.6Hz,3H),0.88(d,J=6.6Hz,3H),0.86(d,J=6.6Hz,3H),0.81(d,J=6.6Hz,3H),0.76(T,J=6.6Hz,3H)( Figure 65 ).

[0226] Carbon NMR spectroscopy test: 13 C NMR (101MHz, CDCl3) δ214.98,164.29,148.12,143.82,137.31,132.99,131.55,129.09,128. 63,128.03,126.80,121.52,96.50,82.07,81.50,72.01,71.55,69.85,69.08,66.38,63.63,4 4.69,44.22,43.93,41.57,40.19,39.12,37.54,34.48,34.20,32.51,30.36,29.64,29.53,28.86,27.22,25.55,23.74,20.66,20.00,17.14,13.86,13.51,11.15,10.27,7.92,7.61,4.28 Figure 66 ).

[0227] Example 23 Synthesis of compound RTM-W-XZW-0677

[0228] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.2 mmol, 2.0 eq.) were dissolved in dichloromethane (5.0 mL), and p-tert-butylbenzenesulfonyl chloride (0.1 mmol, 1.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0229]

[0230] Mass spectrometry analysis of the synthetic route of RTM-W-XZW-0677: Molecular formula of RTM-W-XZW-0677 C 54 H 84 O 13 S, molecular weight 972 ( Figure 67 ).

[0231] ¹H NMR spectroscopy: 1H NMR (400MHz, CDCl₃) δ 7.73–7.70 (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) ,0.94(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 ).

[0232] Carbon NMR spectroscopy: 13C NMR (101MHz, CDCl3) δ 215.05, 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 ).

[0233] Example 24 Synthesis of compound RTM-LHY-0368

[0234] Synthetic 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 weighed and dissolved in dichloromethane (5 mL). The mixture was stirred at 0 °C for 30 min, and oxaloyl chloride monomethyl ester (191.12 mg, 1.56 mmol, 6.00 eq.) was slowly added dropwise. The mixture was then transferred to room temperature and reacted for 6 h. After the reaction was completed by TLC monitoring, the solvent was removed under reduced pressure. Column chromatography yielded 90.00 mg of product (white solid, yield 45%).

[0235]

[0236] Mass spectrometry analysis of the RTM-LHY-0368 synthesis route: RTM-LHY-0368 molecular formula C 50 H 76 O 17 Molecular weight 948 Figure 70 ).

[0237] 1H NMR spectroscopy: 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),3.64-3.5 9(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 ).

[0238] Carbon NMR spectroscopy 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. 50,146.92,137.77,133.87,130.50,128.61,124.08,97.34,83.02,80.61,76.78,72.76,70.79,69.64,67.81 ,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 ).

[0239] Example 25 Synthesis of compound RTM-XZW-0302

[0240] Synthetic method: Rutamycin (77.7 mg, 0.1 mmol, 1.0 eq.) and DMAP (0.1 mmol, 1.0 eq.) were dissolved in dichloromethane (5.0 mL), and ethylsulfonyl chloride (0.2 mmol, 2.0 eq.) was added. The reaction was carried out at room temperature for 4 h. After the reaction was completed, the mixture was extracted with water and ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain the crude product. The crude product was purified by silica gel column chromatography to obtain a white solid.

[0241]

[0242] Mass spectrometry analysis of the synthesis route of RTM-XZW-0302: Molecular formula of RTM-XZW-0302 C 48 H 80 O 15 S2, molecular weight 960 ( Figure 73 ).

[0243] 1H NMR spectroscopy: 1 HNMR(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 .40(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,1 H),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,6 H),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 ).

[0244] Carbon NMR spectroscopy: 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 ).

[0245] Example 26 Synthesis of compound RTM-0211

[0246] To synthesize compound RTM-0211, the starting material RTM was dissolved in tetrahydrofuran, and p-nitrobenzoic acid, triphenylphosphine, and ethyl azodicarbonate were added for reaction. After the first step, the resulting product was dissolved in a solution of tetrahydrofuran and methanol, potassium carbonate was added, and hydrolysis was performed to obtain the target product RTM-0211. The configuration of the hydroxyl groups at positions 5, 9, 12, 13, and 33 of RTM can be inverted to give the target compound RTM-0211, with a yield of 53%. The 1H NMR spectrum of RTM-A-24 showed that its structure was different from that of RTM, with a significant difference in the proton peaks between 1.0 and 3.0 ppm. High-resolution mass spectrometry showed that the m / z of RTM-0211 was 776.5075, consistent with that of RTM, indicating that RTM-0211 is the product of the configuration inversion of the hydroxyl groups in RTM.

[0247]

[0248] RTM-0211 Synthesis Route

[0249] Example 27 Synthesis of compound RTM-0212

[0250] To synthesize compound RTM-0212, the starting material RTM was dissolved in ethanol, and hydrochloric acid and hydrazine were added to initiate the reaction. The carbonyl group at the 7-position of RTM underwent an oxime formation reaction, yielding the target compound RTM-0212. The 1H NMR spectrum of RTM-0212 showed that its structure differed from RTM, with significant differences in the hydrogen atoms with chemical shifts between 1.0 and 3.0. Mass spectrometry indicated that the molecular weight of RTM-0212 was 790, suggesting that the product exhibited structural characteristics consistent with RTM-0212.

[0251] Example 28: Inhibition rate test of RTM and its derivatives against Fusarium graminearum, the causal agent of wheat blight.

[0252] The inhibition rate of 20 mg / L RTM and its derivatives against Fusarium graminearum, the causal agent of wheat blight, was determined using the pathogen mycelial growth method (Table 1).

[0253] Table 1. Inhibition rate of 20 mg / L RTM derivatives against Fusarium graminearum, the causal agent of wheat blight.

[0254]

[0255] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and variations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. The following compounds, or their pharmaceutically acceptable salts, tautomers, and stereoisomers, as shown in Formula I: Formula I; R1 is selected from -N3, -OS(=O)(=O)-benzene ring-Cl; R2 and R3 are selected from H, and a double bond is formed between the C connected to R2 and the C connected to R3; R4 is selected from -OH; R5 is selected from =O; R6 is selected from -OH; R7 is selected from -OH; R 8、 R 9、 R 10 With R 11 Selected from H, the C bond connected to R8 and the C bond connected to R9 form a double bond, R 10 Connected C and R 11 The connected carbons form a double bond; or the carbons connected to R8 and R9 are connected by an oxygen atom to form a three-membered ring ether. 10 Connected C and R 11 The connected C atoms form a double bond.

2. A compound or its pharmaceutically acceptable salt, tautomer, or stereoisomer, characterized in that, The compound's structural formula is selected from one of the following: 。 3. The use of the compound according to claim 1 or 2, or its pharmaceutically acceptable salts, tautomers, or stereoisomers, in the agricultural field for the prevention and control of wheat scab.

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