CN116143736B - 1-Oxo-acetyl inula lactone derivative and application thereof - Google Patents

1-Oxo-acetyl inula lactone derivative and application thereof Download PDF

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CN116143736B
CN116143736B CN202310261528.3A CN202310261528A CN116143736B CN 116143736 B CN116143736 B CN 116143736B CN 202310261528 A CN202310261528 A CN 202310261528A CN 116143736 B CN116143736 B CN 116143736B
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CN116143736A (en
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杨春
张媛
郅晓燕
李杨凡
曹挥
郝晓娟
时宏程
李杨
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Shanxi Agricultural University
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Abstract

The invention discloses a 1-oxygen-acetyl inula lactone derivative and application thereof. Taking a natural sesquiterpene lactone compound 1-O-acetyl inula lactone as a raw material, and introducing a1, 3, 4-oxadiazole or 1,2, 4-triazole heterocyclic structure with a bacteriostasis effect into a 1-O-acetyl inula lactone molecular skeleton by different chemical means to obtain a 1-O-acetyl inula lactone derivative; the antibacterial activity test result shows that part of the derivatives have strong growth inhibition or germination inhibition effects on hyphae or spores of plant pathogenic fungi to be tested, so the derivatives are expected to be used for preparing novel agricultural antibacterial agents with high efficiency and broad spectrum.

Description

1-Oxo-acetyl inula lactone derivative and application thereof
Technical Field
The invention belongs to the technical field of synthesis and application of bactericides, and particularly relates to a derivative of 1-oxo-acetyl inula flower lactone containing a1, 3, 4-oxadiazole/1, 2, 4-triazole heterocyclic structure and application thereof.
Background
1-Oxo-acetylinula lactone (1-O-acetylbritannilactone) is a natural sesquiterpene lactone compound isolated from Inula britannica L. The prior literature reports that the substance has certain inhibition effect on various plant pathogenic bacteria and has great potential for further developing into novel plant source antibacterial agents. Among them, document [ Wang Gonggang, wang Wenqiao, han Xiuying, etc. ], analysis of isolation of 1-oxo-acetyl inula lactone in inula, determination of antibacterial activity, report of plant protection, 2008,35 (6): 551-556.], and document [ Ding Haixin, li Anze, feng Juntao, etc. ], isolation and identification of bactericidal active ingredients of inula, university of northwest agriculture and forestry science and technology (Nature science edition), 2005,33 (3): 90-94.], report that 1-oxo-acetyl inula lactone in Inula eurasia has remarkable inhibitory activity against various plant pathogenic fungi. Meanwhile, literature [ Zhou Lin, jiao, gaofu et al, the antibacterial activity of different solvent extracts of inula flower inflorescences on plant pathogenic fungi, university of Zhejiang (agricultural and life sciences edition), 2010,36 (3): 287-292 ] and literature [ Mo Gongjuan, zhao Te, dong Gong et al, the study of the biological activity of extracts of different parts of inula flowers on phytophthora capsici, university of Henan agricultural report, 2012,46 (3): 313-316 ], report that 1-oxo-acetylinula lactone homologue 1, 6-dioxo-diacetyl inula flower lactone (DABL) in inula flowers also has a good antibacterial effect, which shows excellent inhibitory effect on phytophthora capsici.
In summary, the literature only reports the antibacterial activity of 1-oxo-acetyl inula lactone, but the antibacterial effect on the derivatives or analogues thereof is rarely related, and the natural product has the limitations of weaker antibacterial activity, narrower activity spectrum, low practical application value and the like, so that the possibility of further developing the novel agricultural antibacterial agent is limited.
Disclosure of Invention
The technical problems to be solved by the invention are as follows: how to modify the 1-oxo-acetyl inula lactone to improve the antibacterial activity or the broad spectrum.
The technical scheme of the invention is as follows: 1-oxo-acetyl inula lactone derivative has a structure shown in a formula I or a pharmaceutically acceptable salt of the structure shown in the formula I:
In formula I, R 1、R2 and R 3 are any one of the following combinations of (1) - (45): (1) R 1＝H,R2＝H,R3＝H;(2)R1＝Cl,R2＝H,R3 =h;
(3)R1＝H,R2＝Br,R3＝H;(4)R1＝H,R2＝Br,R3＝Br；
(5)R1＝H,R2＝H,R3＝Br;(6)R1＝R-a,R2＝H,R3＝H；
(7)R1＝R-b,R2＝H,R3＝H;(8)R1＝R-c,R2＝H,R3＝H；
(9)R1＝R-d,R2＝H,R3＝H;(10)R1＝R-e,R2＝H,R3＝H；
(11)R1＝R-f,R2＝H,R3＝H;(12)R1＝R-g,R2＝H,R3＝H;(13)R1＝R-h,R2＝H,R3＝H;(14)R1＝R-i,R2＝H,R3＝H;(15)R1＝R-j,R2＝H,R3＝H;(16)R1＝R-k,R2＝H,R3＝H;(17)R1＝R-l,R2＝H,R3＝H;(18)R1＝R-m,R2＝H,R3＝H;(19)R1＝R-n,R2＝H,R3＝H;(20)R1＝R-p,R2＝H,R3＝H;(21)R1＝H,R2＝R-a,R3＝H;(22)R1＝H,R2＝R-b,R3＝H;(23)R1＝H,R2＝R-d,R3＝H;(24)R1＝H,R2＝R-f,R3＝H;(25)R1＝H,R2＝R-g,R3＝H;(26)R1＝H,R2＝R-h,R3＝H;(27)R1＝H,R2＝R-i,R3＝H;(28)R1＝H,R2＝R-j,R3＝H;(29)R1＝H,R2＝R-k,R3＝H;(30)R1＝H,R2＝R-l,R3＝H;(31)R1＝H,R2＝R-m,R3＝H;(32)R1＝H,R2＝R-n,R3＝H;(33)R1＝H,R2＝R-o,R3＝H;(34)R1＝H,R2＝R-p,R3＝H;(35)R1＝H,R2＝R-q,R3＝H;(36)R1＝H,R2＝R-R,R3＝Br;(37)R1＝H,R2＝R-d,R3＝Br;(38)R1＝H,R2＝R-h,R3＝Br;(39)R1＝H,R2＝R-i,R3＝Br;(40)R1＝H,R2＝R-j,R3＝Br;(41)R1＝H,R2＝R-k,R3＝Br;(42)R1＝H,R2＝R-l,R3＝Br;(43)R1＝H,R2＝R-n,R3＝Br;(44)R1＝H,R2＝R-p,R3＝Br;
(45)R1＝H,R2＝R-q,R3＝Br；
Wherein R-a to R-q are each the following groups:
Further, the compound has a structure shown in a formula II or a pharmaceutically acceptable salt of the structure shown in the formula II
The derivatives are applied to plant pathogenic fungi bacteriostats.
Further, the plant pathogenic fungi are any one of apple tree rot germ (Cytospora mandshurica), wheat gibberella (Fusarium graminearum), tomato early blight germ (ALTERNARIA SOLANI), fusarium solani (Fusarium solani), cucumber anthracnose germ (Colletotrichum orbiculare), pepper blight germ (Fusarium oxysporum) or tomato gray mold germ (Botrytis cinerea).
A preparation contains the above derivatives.
Compared with the prior art, the invention has the following beneficial effects:
According to the invention, 1,3, 4-oxadiazole and 1,2, 4-triazole heterocyclic structures are introduced into the molecular skeleton of 1-O-acetyl inula lactone for the first time, so that a series of 1-O-acetyl inula lactone derivatives are prepared. The antibacterial activity test result shows that the prepared 1-oxo-acetylinula lactone derivative has higher antibacterial activity, especially the inhibition activities of the derivatives 2, 7, 13, 15 and 30 on tomato early blight bacteria, fusarium solani and cucumber anthracnose bacteria are all higher than that of parent 1-oxo-acetylinula lactone, wherein the inhibition effect of the derivative 2 on all tested plant pathogenic fungus hyphae is stronger, the inhibition activity is even higher than that of a positive control agent difenoconazole, the inhibition germination effect of the derivative 2 on tomato gray mold fungus spores is also better than that of difenoconazole, and the derivative has larger application potential.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of Compound 2;
FIG. 2 is a nuclear magnetic resonance carbon spectrum of Compound 2;
FIG. 3 is a nuclear magnetic resonance hydrogen spectrum of compound 15;
FIG. 4 is a nuclear magnetic resonance carbon spectrum of compound 15;
FIG. 5 is a nuclear magnetic resonance hydrogen spectrum of compound 19;
FIG. 6 is a nuclear magnetic resonance carbon spectrum of compound 19;
FIG. 7 is a nuclear magnetic resonance hydrogen spectrum of compound 21;
FIG. 8 is a nuclear magnetic resonance carbon spectrum of compound 21.
Detailed Description
The experimental methods in the following examples are conventional methods unless otherwise specified. The test materials used in the examples described below, unless otherwise specified, were purchased from commercial sources.
Example 1
The preparation route and structural characterization data of the 1-O-acetyl inula lactone derivative containing 1,3, 4-oxadiazole/1, 2, 4-triazole heterocyclic structure
The following are routes for the preparation of derivatives 1 and 2:
a certain amount of 1-O-acetyl inula lactone (1 mmol) is dissolved in anhydrous dichloromethane (3 mL), triethylamine (2 mmol) is added into the mixture, the mixture is stirred at room temperature for 5min, acetyl chloride/chloroacetyl chloride (2 mmol) is diluted by 2mL of anhydrous dichloromethane and then is added into the mixture dropwise, the mixture is continuously stirred for half an hour until the raw materials are reacted completely, the mixture is concentrated under reduced pressure, and the target products 1 and 2 are respectively obtained by silica gel thin layer chromatography separation.
The reaction formula is as follows:
The physicochemical properties of compound 1 are as follows:
1) White solid, melting point 84.8-85.6 ℃ and yield 77.5%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝6.37(d,J＝2.8Hz,1H,13-Ha),5.94(d,J＝2.4Hz,1H,13-Hb),5.21(d,J＝1.6Hz,1H,6-H),4.92–4.96(m,1H,8-H),3.89–3.99(m,2H,1-H),3.46–3.49(m,1H,7-H),2.65–2.74(m,2H,4-H and 9-Ha),2.51(dd,J＝2.0,16.0Hz,1H,9–Hb),2.05(s,3H,1-AcO),2.04(s,3H,6-AcO),1.80(s,3H,14-H),1.35–1.44(m,1H,2-Ha),1.23–1.28(m,2H,2-Hb and 3-Ha),0.99–1.07(m,1H,3-Hb),0.89(d,J＝7.2Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝170.92,170.60,169.24,136.01,133.54,131.75,124.72,74.67,68.97,63.96,42.61,34.28,32.80,30.81,26.22,21.01,20.70,20.23,18.16;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 373.1628 (calcd.373.1627for C 19H26O5Na,[M+Na]+).
The physicochemical properties of compound 2 are as follows:
1) White solid, melting point 97.6-98.4 ℃ and yield 82.6%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝6.40(d,J＝2.8Hz,1H,13-Ha),5.95(d,J＝2.4Hz,1H,13-Hb),5.28(d,J＝1.6Hz,1H,6-H),4.94–4.97(m,1H,8-H),4.02(s,2H,-CH2Cl-),3.87–3.99(m,2H,1-H),3.50–3.53(m,1H,7-H),2.66–2.74(m,2H,4-H and 9-Ha),2.54(dd,J＝2.4,16.4Hz,1H,9-Hb),2.04(s,3H,1-AcO),1.82(s,3H,14-H),1.36–1.43(m,1H,2-Ha),1.26–1.30(m,2H,2-Hb and 3-Ha),0.98–1.06(m,1H,3-Hb),0.89(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.18,169.23,167.22,135.90,134.95,131.36,125.33,74.56,71.20,64.16,42.79,40.94,34.57,33.01,31.10,26.50,20.97,20.59,18.57;
3) High resolution mass spectrum characteristics of the compound:
ionization by electrospray ：m/z＝407.1234(calcd.407.1237for C19H25 35ClO6Na,[M+Na]+);409.1210(calcd.409.1208for C19H25 37ClO6Na,[M+Na]+).
The following is a route for the preparation of derivatives 3-5:
Taking a certain amount of compound 1 (1 mmol), N-bromosuccinimide (NBS, 1 mmol) and benzoyl peroxide (BPO, 0.1 mmol) in a flask, adding 3mL of carbon tetrachloride, stirring at 80 ℃ for 2.5h, reacting completely, concentrating under reduced pressure, and preparing silica gel thin layer chromatography to separate to obtain the required target product 3-5.
The reaction formula is as follows:
Compounds 3-5 correspond one-to-one to the sequence numbers of substituents R 4 and R 5.
The physicochemical properties of compound 3 are as follows:
1) Pale yellow gummy liquid with a yield of 36.6%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝6.39(d,J＝2.8Hz,1H,13-Ha),5.95(d,J＝2.4Hz,1H,13-Hb),5.28(d,J＝2.0Hz,1H,6-H),4.99–5.02(m,1H,8-H),4.13(d,J＝10.0Hz,1H,14-Ha),3.92(d,J＝10.0Hz,1H,14-Hb),3.94–4.01(m,2H,1-H),3.50–3.53(m,1H,7-H),2.84(dd,J＝3.6,16.0Hz,1H,9-Ha),2.70–2.75(m,1H,4-H),2.69(dd,J＝2.4,16.4Hz,1H,9-Hb),2.07(s,3H,1-AcO),2.04(s,3H,6-AcO),1.41–1.47(m,1H,2-Ha),1.26–1.33(m,2H,2-Hb and 3-Ha),1.07–1.12(m,1H,3-Hb),0.94(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.17,170.59,169.07,138.11,135.61,133.10,125.46,74.28,68.63,64.00,42.64,33.58,32.33,31.69,30.60,26.60,21.22,20.96,18.14;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝451.0732(calcd.451.0732for C19H25O6Na79Br,[M+Na]+);453.0712(calcd.453.0712for C19H25O6Na81Br,[M+Na]+).
The physicochemical properties of compound 4 are as follows:
1) Pale yellow gummy liquid with a yield of 20.8%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝6.48(d,J＝2.8Hz,1H,13-Ha),6.11(d,J＝2.4Hz,1H,13-Hb),5.24(d,J＝1.2Hz,1H,6-H),5.16(dd,J＝1.6,7.6Hz,1H,8-H),4.91(d,J＝1.6Hz,1H,9-H),4.24(d,J＝10.8Hz,1H,14-Ha),3.97(d,J＝10.8Hz,1H,14-Hb),3.91–4.01(m,2H,1-H),3.71–3.74(m,1H,7-H),2.77–2.80(m,1H,4-H),2.10(s,3H,1-AcO),2.04(s,3H,6-AcO),1.50–1.56(m,1H,2-Ha),1.30–1.37(m,2H,2-Hb and3-Ha),1.17–1.21(m,1H,3-Hb),0.96(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.17,170.74,167.67,143.16,135.04,134.23,126.73,77.71,68.38,63.86,41.49,41.40,34.41,30.52,27.99,26.63,21.43,20.97,17.63;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝528.9832(calcd.528.9837for C19H24O6Na79Br2,[M+Na]+);530.9813(calcd.530.9817for C19H24O6Na79Br81Br,[M+Na]+);532.9796(calcd.532.9796for C19H24O6Na81Br2,[M+Na]+).
The physicochemical properties of compound 5 are as follows:
1) Pale yellow gummy liquid with a yield of 40.5%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝6.45(d,J＝2.8Hz,1H,13-Ha),6.10(d,J＝2.4Hz,1H,13-Hb),5.17(d,J＝1.2Hz,1H,6-H),5.13(dd,J＝1.6,8.0Hz,1H,8-H),4.60(d,J＝1.6Hz,1H,9-H),3.89–3.96(m,2H,1-H),3.68–3.72(m,1H,7-H),2.69–2.74(m,1H,4-H),2.09(s,3H,1-AcO),2.04(s,3H,6-AcO),1.91(s,3H,14-H),1.35–1.42(m,1H,2-Ha),1.20–1.32(m,2H,2-Hb and 3-Ha),1.05–1.13(m,1H,3-Hb),0.91(d,J＝7.2Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.11,171.05,168.15,137.78,135.63,133.93,126.39,78.22,68.75,63.98,45.47,41.53,34.07,30.96,26.43,21.51,20.94,18.53,17.73;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝451.0739(calcd.451.0732for C19H25O6 79BrNa,[M+Na]+);453.0721(calcd.453.0712for C19H25O6 81BrNa,[M+Na]+).
The following is a route for the preparation of derivatives 6-20:
A certain amount of compound 2 (1 mmol), aryloxadiazole heterocycle (R 6 H,1 mmol), potassium carbonate (1 mmol) and potassium iodide (0.1 mmol) was taken, 2mL of acetone was added, the reaction was stirred at room temperature and the progress of the reaction was followed. After the reaction is completed, the solvent is removed by decompression concentration, and the required target product 6-15 is obtained by preparing silica gel thin layer chromatography and separating.
A certain amount of compound 2 (1 mmol), aryltriazole heterocycle (R 7 H,1 mmol), potassium carbonate (1 mmol) and potassium iodide (0.1 mmol) was taken, 2mL of acetone was added, the reaction was stirred at room temperature and the progress of the reaction was followed. After the reaction is completed, the solvent is removed by decompression concentration, and the required target product 16-20 is obtained by preparing silica gel thin layer chromatography and separating.
The reaction formula is as follows:
Compounds 6-20 correspond one-to-one to the sequence numbers of substituents R 6 and R 7.
The physicochemical properties of compound 6 are as follows:
1) Pale yellow gummy liquid with a yield of 61.8%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.98–8.00(m,2H,Ph-H),7.48–7.56(m,3H,Ph-H),6.36(d,J＝2.8Hz,1H,13-Ha),5.90(d,J＝2.4Hz,1H,13-Hb),5.28(d,J＝1.6Hz,1H,6-H),4.97–5.00(m,1H,8-H),3.88–4.09(m,4H,-CH2S-and 1-H),3.58–3.60(m,1H,7-H),2.64–2.71(m,2H,4-H and 9-Ha),2.50(dd,J＝2.0,16.0Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.78(s,3H,14-H),1.35–1.43(m,1H,2-Ha),1.23–1.28(m,2H,2-Hb and 3-Ha),0.96–1.02(m,1H,3-Hb),0.90(d,3H,J＝7.2Hz,15-H).–13C NMR(100MHz,CDCl3):δ＝171.19,169.41,167.57,166.32,162.73,136.08,134.98,131.99,131.29,129.15,126.70,125.07,123.24,74.79,71.33,64.18,42.42,34.54,34.28,32.99,31.11,26.48,20.97,20.53,18.59;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 527.1858 (calcd.527.1852for C 27H31N2O7S,[M+H]+).
The physicochemical properties of compound 7 are as follows:
1) Pale yellow gummy liquid with a yield of 56.4%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.90–7.94(m,2H,Ph-H),6.98–7.01(m,2H,Ph-H),6.36(d,J＝2.8Hz,1H,13-Ha),5.90(d,J＝2.4Hz,1H,13-Hb),5.27(d,J＝1.6Hz,1H,6-H),4.96–4.99(m,1H,8-H),3.89–4.06(m,4H,-CH2S-and 1-H),3.88(s,3H,-OMe),3.57–3.60(m,1H,7-H),2.64–2.70(m,2H,9-Ha and 4-H),2.49(dd,J＝2.0,16.4Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.77(s,3H,14-H),1.40–1.43(m,1H,2-Ha),1.23–1.27(m,2H,2-Hb and 3-Ha),0.98–1.04(m,1H,3-Hb),0.90(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.20,169.44,167.63,166.29,162.51,161.92,136.10,134.97,131.29,128.51,125.06,115.71,114.58,74.82,71.29,64.20,55.50,42.42,34.53,34.30,32.99,31.11,26.48,20.98,20.53,18.59;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 579.1781 (calcd.579.1777for C 28H32N2O8NaS,[M+Na]+).
The physicochemical properties of compound 8 are as follows:
1) Pale yellow gummy liquid with a yield of 69.2%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.89–7.92(m,2H,Ph-H),7.50–7.53(m,2H,Ph-H),6.36(d,J＝2.4Hz,1H,13-Ha),5.90(d,J＝2.0Hz,1H,13-Hb),5.28(d,J＝1.6Hz,1H,6-H),4.96–4.99(m,1H,8-H),3.89–4.07(m,4H,-CH2S-and 1-H),3.57–3.60(m,1H,7-H),2.64–2.70(m,2H,9-Ha and 4-H),2.49(dd,J＝2.0,16.4Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.78(s,3H,14-H),1.40–1.51(m,1H,2-Ha),1.35(s,9H,-C(CH3)3),1.23–1.28(m,2H,2-Hb and 3-Ha),0.96–1.02(m,1H,3-Hb),0.90(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.20,169.43,167.60,166.44,162.34,155.68,136.09,134.97,131.29,126.54,126.13,125.07,120.38,74.81,71.29,64.19,42.42,35.12,34.53,34.28,32.99,31.08,26.48,20.98,20.52,18.59;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 605.2294 (calcd.605.2297for C 31H38N2O7SNa,[M+Na]+).
The physicochemical properties of compound 9 are as follows:
1) Pale yellow gummy liquid with a yield of 57.8%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.98(t,J＝3.2Hz,1H,Ph-H),7.90(dt,J＝2.8,7.6Hz,1H,Ph-H),7.50–7.53(m,1H,Ph-H),7.47(t,J＝7.6Hz,1H,Ph-H),6.36(d,J＝2.4Hz,1H,13-Ha),5.90(d,J＝2.4Hz,1H,13-Hb),5.28(d,J＝1.6Hz,1H,6-H),4.97–5.00(m,1H,8-H),3.89–4.09(m,4H,-CH2S-and 1-H),3.58–3.60(m,1H,7-H),2.65–2.72(m,2H,9-Ha and 4-H),2.51(dd,J＝2.0,16.0Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.79(s,3H,14-H),1.37–1.45(m,1H,2-Ha),1.23–1.27(m,2H,2-Hband 3-Ha),0.96–1.02(m,1H,3-Hb),0.90(d,3H,J＝6.8Hz,H-15).–13C NMR(100MHz,CDCl3):δ＝171.19,169.38,167.48,165.15,163.32,136.05,135.33,135.00,132.02,131.29,130.54,126.67,125.10,124.84,124.76,74.75,71.41,64.18,42.43,34.55,34.27,32.99,31.11,26.48,20.98,20.55,18.60;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝583.1280(calcd.583.1282for C27H29N2O7NaS35Cl,[M+Na]+);585.1260(calcd.585.1252for C27H29N2O7NaS37Cl,[M+Na]+).
The physicochemical properties of compound 10 are as follows:
1) Pale yellow gummy liquid with a yield of 67.4%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.97–8.01(m,2H,Ph-H),7.17–7.23(m,2H,Ph-H),6.36(d,J＝2.4Hz,1H,13-Ha),5.90(d,J＝2.4Hz,1H,13-Hb),5.28(d,J＝2.0Hz,1H,6-H),4.97–5.00(m,1H,8-H),3.88–4.09(m,4H,-CH2S-and 1-H),3.58–3.60(m,1H,7-H),2.67–2.72(m,2H,9-Ha and 4-H),2.51(dd,J＝2.0,16.0Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.79(s,3H,14-H),1.37–1.44(m,1H,2-Ha),1.23–1.28(m,2H,2-Hb and 3-Ha),0.96–1.02(m,1H,3-Hb),0.90(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.20,169.40,167.55,165.50,162.80,136.07,134.99,131.30,129.07,128.98,125.09,116.67,116.44,74.78,71.37,64.18,42.42,34.55,34.28,32.99,31.11,26.48,20.98,20.55,18.60;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 567.1580 (calcd.567.1577for C 27H29N2O7NaSF,[M+Na]+).
The physicochemical properties of compound 11 are as follows:
1) Pale yellow gummy liquid, yield 47.9%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.84–7.87(m,2H,Ph-H),7.63–7.67(m,2H,Ph-H),6.36(d,J＝2.4Hz,1H,13-Ha),5.90(d,J＝2.4Hz,1H,13-Hb),5.28(d,J＝1.6Hz,1H,6-H),4.97–5.00(m,1H,8-H),3.88–4.09(m,4H,-CH2S-and 1-H),3.57–3.60(m,1H,7-H),2.65–2.72(m,2H,4-H and 9-Ha),2.51(dd,J＝2.4,16.4Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.79(s,3H,14-H),1.36–1.44(m,1H,2-Ha),1.24–1.27(m,2H,2-Hb and 3-Ha),0.97–1.05(m,1H,3-Hb),0.90(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.20,169.38,167.51,165.61,163.09,136.05,134.99,132.53,131.29,128.07,126.72,125.10,122.13,74.76,71.40,64.18,42.41,34.55,34.27,32.99,31.11,26.48,20.98,20.55,18.60;
3) High resolution mass spectrum characteristics of the compound:
ionization by electrospray ：m/z＝627.0778(calcd.627.0777for C27H29N2O7S79BrNa,[M+Na]+);629.0764(calcd.629.0756for C27H29N2O7S81BrNa,[M+Na]+).
The physicochemical properties of compound 12 are as follows:
1) Pale yellow gummy liquid with a yield of 52.8%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝8.36–8.39(m,2H,Ph-H),8.17–8.21(m,2H,Ph-H),6.37(d,J＝2.8Hz,1H,13-Ha),5.90(d,J＝2.4Hz,1H,13-Hb),5.29(d,J＝1.6Hz,1H,6-H),4.99–5.02(m,1H,8-H),3.90–4.13(m,4H,-CH2S-and 1-H),3.58–3.61(m,1H,1H,7-H),2.66–2.74(m,2H,9-Ha and 4-H),2.53(dd,J＝2.0,16.4Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.80(s,3H,14-H),1.38–1.45(m,1H,2-Ha),1.24–1.28(m,2H,2-Hb and 3-Ha),0.98–1.05(m,1H,3-Hb),0.91(d,3H,J＝6.8Hz,15-H).–13C NMR(100MHz,CDCl3):δ＝171.20,169.35,167.38,164.55,164.51,149.63,136.01,135.05,131.29,128.67,127.61,125.14,124.49,74.72,71.53,64.16,42.43,34.58,34.30,33.00,31.11,26.49,20.98,20.58,18.62;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 594.1525 (calcd.594.1522for C 27H29N3O9NaS,[M+Na]+).
The physicochemical properties of compound 13 are as follows:
1) Pale yellow gummy liquid with a yield of 61.8%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.64–7.65(m,1H,Furan-H),7.14(d,J＝3.2Hz,1H,Furan-H),6.61(dd,J＝2.0,3.6Hz,1H,Furan-H),6.36(d,J＝2.8Hz,1H,13-Ha),5.90(d,J＝2.4Hz,1H,13-Hb),5.28(d,J＝2.0Hz,1H,6-H),4.97–5.00(m,1H,8-H),3.89–4.07(m,4H,-CH2S-and 1-H),3.57–3.60(m,1H,7-H),2.64–2.71(m,2H,9-Ha and 4-H),2.51(dd,J＝2.0,16.0Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.78(s,3H,14-H),1.36–1.43(m,1H,2-Ha),1.23–1.27(m,2H,2-Hb and 3-Ha),0.96–1.04(m,1H,3-Hb),0.90(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.20,169.41,167.48,162.29,159.00,145.96,138.69,136.08,135.01,131.27,125.07,114.35,112.28,74.78,71.37,64.19,42.41,34.54,34.34,32.98,31.12,26.48,20.98,20.52,18.58;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 539.1471 (calcd.539.1464 for C 25H28N2O8NaS,[M+Na]+).
The physicochemical properties of compound 14 are as follows:
1) A pale yellow gummy liquid, 57.2% was recovered;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.71(dd,J＝0.8,3.6Hz,1H,Thiophene-H),7.57(dd,J＝0.8,4.2Hz,1H,Thiophene-H),7.16–7.18(m 1H,Thiophene-H),6.36(d,J＝2.4Hz,1H,13-Ha),5.90(d,J＝2.4Hz,1H,13-Hb),5.28(d,J＝1.6Hz,1H,6-H),4.96–5.00(m,1H,8-H),3.86–4.07(m,4H,-CH2S-and 1-H),3.59(dd,J＝2.0,8.0Hz,1H,7-H),2.63–2.71(m,2H,4-H and 9-Ha),2.50(dd,J＝2.0,16.4Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.78(s,3H,14-H),1.36–1.45(m,1H,2-Ha),1.24–1.27(m,2H,2-Hb and 3-Ha),0.96–1.02(m,1H,3-Hb),0.90(d,3H,J＝6.8Hz,15-H).–13C NMR(100MHz,CDCl3):δ＝171.20,169.41,167.51,162.48,162.11,136.08,135.00,131.28,130.47,129.94,128.25,125.08,124.36,74.78,71.35,64.19,42.43,34.54,34.31,32.99,31.11,26.48,20.98,20.52,18.59;
3) High resolution mass spectrum characteristics of the compound:
ionization by electrospray ：m/z＝555.1238(calcd.555.1236for C25H28N2O7S2Na,[M+Na]+).
The physicochemical properties of compound 15 are as follows:
1) White solid, melting point 134.8-135.7 ℃ and yield 50.9%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝8.77(d,J＝4.4Hz,1H,Py-H),8.19(d,J＝8.0Hz,1H,Py-H),7.92(td,J＝1.6,7.6Hz,1H,Py-H),7.46–7.49(m,1H,Py-H),6.36(d,J＝2.4Hz,1H,13-Ha),5.90(d,J＝2.4Hz,1H,13-Hb),5.29(d,J＝1.6Hz,1H,H-6),4.97–5.01(m,1H,8-H),3.89–4.11(m,4H,-CH2S-and 1-H),3.61–3.64(m,1H,7-H),2.64–2.72(m,2H,9-Ha and 4-H),2.50(dd,J＝2.4,16.4Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.78(s,3H,14-H),1.35–1.42(m,1H,2-Ha),1.23–1.30(m,2H,2-Hband 3-Ha),0.97–1.05(m,1H,3-Hb),0.91(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.19,169.43,167.45,165.38,164.35,150.35,142.92,136.08,134.96,131.30,126.07,125.07,122.93,74.80,71.33,64.19,42.39,34.55,34.25,32.99,31.11,26.48,20.98,20.53,18.59;
3) High resolution mass spectrum characteristics of the compound:
electrospray ionization is adopted: m/z= 550.1629 (calcd.550.1624for C 26H29N3O7NaS,[M+Na]+).
The physicochemical properties of compound 16 are as follows:
1) White solid, melting point 54.3-55.1 ℃ and yield 56.7%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.52–7.57(m,3H,Ph-H),7.37–7.44(m,3H,Ph-H),7.29–7.32(m,4H,Ph-H),6.35(d,J＝2.4Hz,1H,13-Ha),5.89(d,J＝2.0Hz,1H,13-Hb),5.27(d,J＝1.2Hz,1H,6-H),5.11–5.13(m,1H,8-H),4.20(d,J＝16.4Hz,1H,-CHaS-),3.89–3.98(m,3H,1-H and-CHbS-),3.71–3.72(m,1H,7-H),2.66–2.77(m,2H,4-H and 9-Ha),2.52(d,J＝15.2Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.80(s,3H,14-H),1.36–1.42(m,1H,2-Ha),1.25–1.28(m,2H,2-Hb and 3-Ha),0.96–1.05(m,1H,3-Hb),0.90(d,J＝7.2Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.22,169.62,168.11,136.44,134.96,133.18,131.33,130.74,130.69,130.38,128.83,128.39,127.11,124.79,75.11,71.32,64.24,42.30,34.62,34.43,33.00,31.15,26.49,20.99,20.58,18.65;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 624.2136 (calcd.624.2144 for C 33H35N3O6SNa,[M+Na]+).
The physicochemical properties of compound 17 are as follows:
1) White solid, melting point of 51.9-52.6 ℃ and yield of 37.8%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.48–7.52(m,3H,Ph-H),7.32(s,1H,Ph-H),7.29(s,1H,Ph-H),7.23–7.26(m,2H,Ph-H),6.80(s,1H,Ph-H),6.78(s,1H,Ph-H),6.35(d,J＝2.8Hz,1H,13-Ha),5.89(d,J＝2.4Hz,1H,13-Hb),5.26(d,J＝1.6Hz,1H,6-H),5.05–5.08(m,1H,8-H),4.03(d,J＝16.0Hz,1H,-CHaS-),3.89–3.99(m,2H,1-H),3.89(d,J＝16.0Hz,1H,-CHbS-),3.77(s,3H,-OMe),3.69–3.71(m,1H,7-H),2.63–2.75(m,2H,4-H and 9-Ha),2.51(dd,J＝1.6,16.0Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.80(s,3H,14-H),1.35–1.42(m,1H,2-Ha),1.25–1.28(m,2H,2-Hb and 3-Ha),0.98–1.05(m,1H,3-Hb),0.89(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.19,169.63,168.45,160.81,155.23,150.82,136.43,134.70,134.03,131.51,130.11,130.08,129.60,127.18,124.78,118.65,114.06,75.09,71.03,64.24,55.28,42.22,34.60,34.29,33.03,31.15,26.51,20.97,20.55,18.60;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 654.2251 (calcd.654.2250for C 34H37N3O7NaS,[M+Na]+).
The physicochemical properties of compound 18 are as follows:
1) White solid with melting point 68.3-69.1 deg.c and yield 88.2%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.49–7.54(m,3H,Ph-H),7.26–7.33(m,6H,Ph-H),6.35(d,J＝2.4Hz,1H,13-Ha),5.89(d,J＝2.0Hz,1H,13-Hb),5.26(d,J＝1.2Hz,1H,6-H),5.06–5.07(m,1H,8-H),4.04(d,J＝16.0Hz,1H,-CHaS-),3.90–3.99(m,2H,1-H),3.90(d,J＝16.0Hz,1H,-CHbS-),3.69–3.71(m,1H,7-H),2.65–2.75(m,2H,4-H and 9-Ha),2.51(dd,J＝1.6,16.4Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.80(s,3H,14-H),1.35–1.42(m,1H,2-Ha),1.26(s,11H,2-Hb,3-Ha and t-Bu),0.98–1.05(m,1H,3-Hb),0.90(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.21,169.65,168.46,155.33,153.35,151.18,136.50,134.76,134.09,131.59,130.18,127.74,127.28,125.64,124.80,123.34,75.13,71.12,64.28,42.29,34.84,34.66,34.33,33.09,31.21,31.14,26.57,21.01,20.60,18.64;
3) High resolution mass spectrum characteristics of the compound:
electrospray ionization is adopted: m/z= 680.2775 (calcd.680.2770for C 37H43N3O6NaS,[M+Na]+).
The physicochemical properties of compound 19 are as follows:
1) White solid, melting point 53.5-54.3 ℃ and yield 58.1%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.51–7.57(m,3H,Ph-H),7.44(s,1H,Ph-H),7.31–7.34(m,1H,Ph-H),7.25–7.27(m,2H,Ph-H),7.20–7.21(m,2H,Ph-H),6.35(d,J＝2.8Hz,1H,13-Ha),5.89(d,J＝2.0Hz,1H,13-Hb),5.27(d,J＝1.6Hz,1H,6-H),5.06–5.09(m,1H,8-H),4.10(d,J＝16.0Hz,1H,-CHaS-),3.93–3.99(m,2H,1-H),3.92(d,J＝16.0Hz,1H,-CHbS-),3.68–3.71(m,1H,7-H),2.66–2.77(m,2H,4-H and 9-Ha),2.52(dd,J＝2.0,16.0Hz,1H,9-Hb),2.03(s,3H,1-AcO),1.81(s,3H,14-H),1.35–1.42(m,1H,2-Ha),1.25–1.28(m,2H,2-Hb and 3-Ha),0.98–1.05(m,1H,3-Hb),0.90(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.18,169.57,168.31,153.92,152.02,136.40,134.79,134.73,133.43,131.48,130.54,130.34,130.16,129.89,128.19,127.77,127.05,126.03,124.80,75.04,71.18,64.22,42.26,34.62,34.30,33.03,31.16,26.52,20.97,20.56,18.61;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝658.1764(calcd.658.1755for C33H34N3O6NaS35Cl,[M+Na]+);660.1740(calcd.660.1725for C33H34N3O6NaS37Cl,[M+Na]+).
The physicochemical properties of compound 20 are as follows:
1) White solid with melting point of 56.7-57.1 ℃ and yield of 33.7%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.43–7.48(m,3H,Ph-H),7.36(s,1H,Ph-H),7.33(s,1H,Ph-H),7.16–7.19(m,4H,Ph-H),6.28(d,J＝2.4Hz,1H,13-Ha),5.82(d,J＝2.0Hz,1H,13-Hb),5.19(d,J＝1.6Hz,1H,6-H),4.97–5.01(m,1H,8-H),3.98(d,J＝16.0Hz,1H,-CHaS-),3.83–3.91(m,2H,1-H),3.83(d,J＝16.0Hz,1H,-CHbS-),3.60–3.63(m,1H,7-H),2.58–2.69(m,2H,4-H and 9-Ha),2.44(dd,J＝2.0,16.4Hz,1H,9-Hb),1.96(s,3H,1-AcO),1.73(s,3H,14-H),1.28–1.35(m,1H,2-Ha),1.16–1.20(m,2H,2-Hb and 3-Ha),0.91–0.98(m,1H,3-Hb),0.82(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝170.16,168.56,167.35,153.37,150.76,135.34,133.71,132.61,130.90,130.48,129.37,129.28,128.43,126.03,124.19,123.80,123.51,74.01,70.09,63.20,41.21,33.58,33.23,32.00,30.12,25.49,19.95,19.54,17.58;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝702.1254(calcd.702.1249for C33H34N3O6NaS79Br,[M+Na]+);704.1240(calcd.704.1229for C33H34N3O6NaS81Br,[M+Na]+).
The following is a route for the preparation of derivatives 21-45:
an amount of compound 3 (1 mmol), aryloxadiazole heterocycle (R 6 H,1 mmol) or aryltriazole heterocycle (R 7 H,1 mmol), potassium carbonate (1 mmol) and potassium iodide (0.1 mmol) were taken, 2mL of acetone was added, the reaction was stirred at room temperature and the progress of the reaction was followed. After the reaction is completed, the solvent is removed by decompression concentration, and the required target products 21-28 or 29-35 are respectively obtained by preparing silica gel thin layer chromatography.
An amount of compound 4 (1 mmol), aryloxadiazole heterocycle (R 6 H,1 mmol) or aryltriazole heterocycle (R 7 H,1 mmol), potassium carbonate (1 mmol) and potassium iodide (0.1 mmol) were taken, 2mL of acetone was added, the reaction was stirred at room temperature and the progress of the reaction was followed. After the reaction is completed, the solvent is removed by decompression concentration, and the target products 36-40 or 41-45 are respectively obtained by silica gel thin layer chromatography separation.
The reaction formula is as follows:
Compounds 21-45 correspond one-to-one to the sequence numbers of substituents R 6 and R 7.
The physicochemical properties of compound 21 are as follows:
1) Pale yellow gummy liquid with a yield of 54.2%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(600MHz,CDCl3):δ＝8.00–8.01(m,2H,Ph-H),7.52–7.54(m,1H,Ph-H),7.49–7.51(m,2H,Ph-H),6.39(d,J＝2.4Hz,1H,13-Ha),5.95(d,J＝2.4Hz,1H,13-Hb),5.26(d,J＝1.8Hz,1H,6-H),4.98–5.01(m,1H,8-H),4.26(d,J＝12.6Hz,1H,14-Ha),3.93–4.00(m,2H,1-H),3.93(d,J＝12.6Hz,1H,14-Hb),3.49–3.51(m,1H,7-H),2.77–2.85(m,3H,9-H and 4-H),2.04(s,3H,1-AcO),2.01(s,3H,6-AcO),1.43–1.48(m,1H,2-Ha),1.25–1.30(m,2H,2-Hb and 3-Ha),1.03–1.08(m,1H,3-Hb),0.88(d,J＝6.6Hz,3H,15-H).–13C NMR(150MHz,CDCl3):δ＝171.13,170.60,169.05,166.17,163.33,139.16,135.64,131.83,130.70,129.11,126.71,125.60,123.52,74.39,68.60,64.05,42.79,35.52,33.69,32.54,30.84,26.69,21.16,20.95,18.39;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 549.1668 (calcd.549.1671for C 27H30N2O7NaS,[M+Na]+).
The physicochemical properties of compound 22 are as follows:
1) Pale yellow gummy liquid with a yield of 38.5%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.93–7.95(m,2H,Ph-H),6.99–7.01(m,2H,Ph-H),6.39(d,J＝2.4Hz,1H,13-Ha),5.95(d,J＝2.0Hz,1H,13-Hb),5.25(d,J＝2.0Hz,1H,6-H),4.98–5.01(m,1H,8-H),4.25(d,J＝12.8Hz,1H,14-Ha),3.92–3.99(m,2H,1-H),3.89(d,J＝12.4Hz,1H,14-Hb),3.88(s,3H,OMe),3.47–3.51(m,1H,7-H),2.76–2.85(m,3H,9-H and 4-H),2.04(s,3H,1-AcO),2.01(s,3H,6-AcO),1.44–1.48(m,1H,2-Ha),1.26–1.29(m,2H,2-Hb and 3-Ha),1.00–1.08(m,1H,3-Hb),0.87(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.16,170.63,169.09,166.16,162.50,162.41,139.01,135.66,130.82,128.51,125.59,116.01,114.54,74.43,68.60,64.06,55.48,42.79,35.57,33.66,32.53,30.84,26.68,21.17,20.96,18.39;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 579.1783 (calcd.579.1777for C 28H32N2O8NaS,[M+Na]+).
The physicochemical properties of compound 23 are as follows:
1) Pale yellow gummy liquid with 66% yield;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝8.01(t,J＝1.6Hz,1H,Ph-H),7.91(dt,J＝1.6,7.6Hz,1H,Ph-H),7.49–7.52(m,1H,Ph-H),7.47(t,J＝8.0Hz,1H,Ph-H),6.39(d,J＝2.4Hz,1H,13-Ha),5.95(d,J＝2.0Hz,1H,13-Hb),5.27(d,J＝2.0Hz,1H,6-H),4.98–5.01(m,1H,8-H),4.25(d,J＝12.8Hz,1H,14-Ha),3.91–4.01(m,2H,1-H),3.97(d,J＝12.4Hz,1H,14-Hb),3.48–3.52(m,1H,7-H),2.75–2.86(m,3H,9-H and 4-H),2.04(s,3H,1-AcO),2.02(s,3H,6-AcO),1.44–1.52(m,1H,2-Ha),1.26–1.32(m,2H,2-Hb and 3-Ha),1.02–1.10(m,1H,3-Hb),0.90(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.14,170.57,169.02,164.97,163.93,139.36,135.59,135.25,131.83,130.48,126.68,125.64,125.12,124.77,74.35,68.58,64.04,42.77,35.43,33.70,32.50,30.80,26.69,21.18,20.96,18.39;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝583.1285(calcd.583.1282for C27H29N2O7NaS35Cl,[M+Na]+);585.1265(calcd.585.1252for C27H29N2O7NaS37Cl,[M+Na]+).
The physicochemical properties of compound 24 are as follows:
1) Pale yellow gummy liquid with a yield of 40.2%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.89(d,J＝8.4Hz,2H,Ph-H),7.66(d,J＝8.4Hz,2H,Ph-H),6.39(d,J＝2.4Hz,1H,13-Ha),5.95(d,J＝2.0Hz,1H,13-Hb),5.27(d,J＝1.6Hz,1H,6-H),4.96–5.00(m,1H,8-H),4.23(d,J＝12.4Hz,1H,14-Ha),3.87–4.02(m,2H,1-H),3.98(d,J＝12.0Hz,1H,14-Hb),3.49–3.51(m,1H,7-H),2.69–2.81(m,3H,9-H and 4-H),2.04(s,3H,1-AcO),2.02(s,3H,6-AcO),1.42–1.49(m,1H,2-Ha),1.25–1.34(m,2H,2-Hb and 3-Ha),1.01–1.07(m,1H,3-Hb),0.89(d,J＝6.4Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.14,170.57,169.03,165.42,163.73,139.35,135.59,132.47,130.53,128.11,126.51,125.64,122.42,74.36,68.58,64.04,42.78,35.42,33.70,32.51,30.79,26.70,21.19,20.97,18.40;
3) High resolution mass spectrum characteristics of the compound:
ionization by electrospray ：m/z＝627.0776(calcd.627.0777for C27H29N2O7S79BrNa,[M+Na]+);629.0759(calcd.629.0756for C27H29N2O7S81BrNa,[M+Na]+).
The physicochemical properties of compound 25 are as follows:
1) Pale yellow gummy liquid with a yield of 58.5%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝8.39(t,J＝2.0Hz,1H,Ph-H),8.37(t,J＝2.0Hz,1H,Ph-H),8.22(t,J＝2.0Hz,1H,Ph-H),8.20(t,J＝2.0Hz,1H,Ph-H),6.39(d,J＝2.4Hz,1H,13-Ha),5.96(d,J＝2.4Hz,1H,13-Hb),5.29(d,J＝2.0Hz,1H,6-H),4.98–5.01(m,1H,8-H),4.19(d,J＝12.8Hz,1H,14-Ha),4.11(d,J＝12.8Hz,1H,14-Hb),3.93–4.01(m,2H,1-H),3.49–3.53(m,1H,7-H),2.81–2.87(m,3H,9-H and 4-H),2.04(s,6H,1-AcO and 6-AcO),1.46–1.53(m,1H,2-Ha),1.27–1.32(m,2H,2-Hb and 3-Ha),1.04–1.11(m,1H,3-Hb),0.93(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.14,170.53,168.99,165.17,164.33,149.52,139.79,135.51,130.19,129.00,127.61,125.71,124.43,74.28,68.55,64.04,42.77,35.24,33.73,32.44,30.74,26.71,21.20,20.97,18.38;
3) High resolution mass spectrum characteristics of the compound:
electrospray ionization is adopted: m/z= 594.1526 (calcd.594.1522for C 27H29N3O9NaS,[M+Na]+).
The physicochemical properties of compound 26 are as follows:
1) Pale yellow gummy liquid with a yield of 69.3%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.64(dd,J＝0.8,1.6Hz,1H,Furan-H),7.14(dd,J＝0.8,3.6Hz,1H,Furan-H),6.60(dd,J＝1.6,3.6Hz,1H,Furan-H),6.39(d,J＝2.8Hz,1H,13-Ha),5.95(d,J＝2.4Hz,1H,13-Hb),5.25(d,J＝2.0Hz,1H,6-H),4.97–5.01(m,1H,8-H),4.27(d,J＝12.4Hz,1H,14-Ha),3.91–4.01(m,2H,1-H),3.88(d,J＝12.8Hz,1H,14-Hb),3.48–3.51(m,1H,7-H),2.74–2.85(m,3H,9-H and 4-H),2.04(s,3H,1-AcO),2.01(s,3H,6-AcO),1.42–1.48(m,1H,2-Ha),1.26–1.30(m,2H,2-Hb and 3-Ha),1.01–1.09(m,1H,3-Hb),0.88(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.16,170.61,169.05,162.77,158.91,145.81,139.27,138.99,135.62,130.54,125.63,114.17,112.22,74.40,68.59,64.05,42.78,35.62,33.66,32.48,30.84,26.66,21.15,20.96,18.32;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 539.1473 (calcd.539.1464 for C 25H28N2O8NaS,[M+Na]+).
The physicochemical properties of compound 27 are as follows:
1) Pale yellow gummy liquid with a yield of 57.9%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.72(dd,J＝1.2,3.6Hz,1H,Thiophene-H),7.56(dd,J＝1.2,5.2Hz,1H,Thiophene-H),7.17(dd,J＝4.0,5.2Hz,1H,Thiophene-H),6.39(d,J＝2.8Hz,1H,13-Ha),5.95(d,J＝2.4Hz,1H,13-Hb),5.25(d,J＝2.0Hz,1H,6-H),4.98–5.01(m,1H,8-H),4.26(d,J＝12.8Hz,1H,14-Ha),3.92–4.01(m,2H,1-H),3.90(d,J＝12.8Hz,1H,14-Hb),3.48–3.51(m,1H,7-H),2.75–2.86(m,3H,9-H and4-H),2.04(s,3H,1-AcO),2.02(s,3H,6-AcO),1.42–1.48(m,1H,2-Ha),1.25–1.29(m,2H,2-Hb and 3-Ha),1.01–1.08(m,1H,3-Hb),0.88(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.15,170.61,169.05,162.67,162.37,139.19,135.63,130.64,130.27,129.82,128.21,125.61,124.70,74.40,68.59,64.05,42.78,35.58,33.67,32.51,30.84,26.68,21.15,20.96,18.38;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝555.1239(calcd.555.1236for C25H28N2O7NaS2,[M+Na]+).
The physicochemical properties of compound 28 are as follows:
1) Pale yellow gummy liquid with a yield of 42.9%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝8.78(d,J＝4.4Hz,1H,Py-H),8.21(d,J＝7.6Hz,1H,Py-H),7.92(td,J＝1.2,7.6,1H,Py-H),7.49(dd,J＝4.8,7.2Hz,1H,Py-H),6.39(d,J＝2.8Hz,1H,13-Ha),5.95(d,J＝2.4Hz,1H,13-Hb),5.26(d,J＝2.0Hz,1H,6-H),4.97–5.01(m,1H,8-H),4.36(d,J＝12.8Hz,1H,14-Ha),3.92–4.01(m,2H,1-H),3.90(d,J＝12.8Hz,1H,14-Hb),3.47–3.51(m,1H,7-H),2.75–2.87(m,3H,9-H and 4-H),2.04(s,3H,1-AcO),2.01(s,3H,6-AcO),1.43–1.50(m,1H,2-Ha),1.25–1.29(m,2H,2-Hb and 3-Ha),1.02–1.09(m,1H,3-Hb),0.89(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.17,170.62,169.03,165.14,164.90,150.25,143.09,139.21,137.43,135.65,130.61,125.93,125.58,122.92,74.43,68.62,64.08,42.78,35.56,33.70,32.57,30.84,26.69,21.20,20.97,18.39;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 550.1619 (calcd.550.1624for C 26H29N3O7NaS,[M+Na]+).
The physicochemical properties of compound 29 are as follows:
1) White solid, melting point 59.3-59.9 deg.C, yield 41.1%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.50–7.52(m,3H,Ph-H),7.39–7.41(m,2H,Ph-H),7.32–7.35(m,1H,Ph-H),7.25–7.29(m,4H,Ph-H),6.36(d,J＝2.4Hz,1H,13-Ha),5.93(d,J＝2.4Hz,1H,13-Hb),5.25(d,J＝1.6Hz,1H,6-H),4.92–4.95(m,1H,8-H),4.19(d,J＝12.8Hz,1H,14-Ha),3.83–3.97(m,2H,1-H),3.92(d,J＝12.4Hz,1H,14-Hb),3.45–3.48(m,1H,7-H),2.75–2.80(m,1H,4-H),2.73(d,J＝2.8Hz,2H,9-H),2.04(s,3H,1-AcO),2.00(s,3H,6-AcO),1.36–1.41(m,1H,2-Ha),1.22–1.25(m,2H,2-Hb and3-Ha),0.96–1.03(m,1H,3-Hb),0.87(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.13,170.63,169.07,155.11,151.97,138.18,135.74,134.04,131.68,130.01,129.87,128.53,128.22,127.41,126.36,125.34,74.40,68.72,64.13,42.73,35.42,33.53,32.44,30.76,26.61,21.26,20.95,18.44;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 602.2332 (calcd.602.2325for C 33H36N3O6S,[M+H]+).
The physicochemical properties of compound 30 are as follows:
1) White solid, melting point 131.5-132.3 ℃, yield 49.9%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.49–7.53(m,3H,Ph-H),7.31–7.35(m,2H,Ph-H),7.27–7.29(m,1H,Ph-H),7.25–7.26(m,1H,Ph-H),6.80(t,J＝2.8Hz,1H,Ph-H),6.78(t,J＝2.4Hz,1H,Ph-H),6.36(d,J＝2.8Hz,1H,13-Ha),5.92(d,J＝2.4Hz,1H,13-Hb),5.24(d,J＝1.6Hz,1H,6-H),4.91–4.95(m,1H,8-H),4.18(d,J＝12.8Hz,1H,14-Ha),3.83–3.96(m,2H,1-H),3.87(d,J＝12.4Hz,1H,14-Hb),3.77(s,3H,-OMe),3.44–3.48(m,1H,7-H),2.73–2.78(m,1H,4-H),2.71–2.73(m,2H,9-H),2.04(s,3H,1-AcO),2.01(s,3H,6-AcO),1.34–1.40(m,1H,2-Ha),1.22–1.25(m,2H,2-Hb and 3-Ha),0.99–1.06(m,1H,3-Hb),0.86(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.13,170.63,169.07,160.77,155.00,151.43,138.08,135.76,134.20,131.75,129.99,129.96,129.71,127.48,125.32,113.99,74.41,68.73,64.13,55.27,42.73,35.49,33.52,32.45,30.76,26.61,21.26,20.95,18.44;
3) High resolution mass spectrum characteristics of the compound:
electrospray ionization is adopted: m/z= 654.2255 (calcd.654.2250for C 34H37N3O7NaS,[M+Na]+).
The physicochemical properties of compound 31 are as follows:
1) White solid, melting point 66.1-66.7 ℃ and yield 26.4%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.51–7.54(m,3H,Ph-H),7.33–7.35(m,2H,Ph-H),7.26–7.30(m,4H,Ph-H),6.36(d,J＝2.8Hz,1H,13-Ha),5.92(d,J＝2.0Hz,1H,13-Hb),5.25(d,J＝1.6Hz,1H,6-H),4.91–4.95(m,1H,8-H),4.18(d,J＝12.8Hz,1H,14-Ha),3.83–3.95(m,2H,1-H),3.91(d,J＝13.2Hz,1H,14-Hb),3.44–3.48(m,1H,7-H),2.75–2.81(m,1H,4-H),2.72(d,J＝2.4Hz,2H,9-H),2.04(s,3H,1-AcO),2.00(s,3H,6-AcO),1.35–1.40(m,1H,2-Ha),1.26(s,11H,2-Hb,3-Ha and t-Bu),1.00–1.06(m,1H,3-Hb),0.86(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.13,170.64,169.07,155.02,153.22,151.78,138.13,135.74,134.16,131.72,130.02,127.79,127.51,125.53,125.34,74.40,68.71,64.14,42.72,35.45,34.77,33.53,32.46,31.08,30.75,26.60,21.26,20.95,18.45;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 680.2767 (calcd.680.2770for C 37H43N3O6NaS,[M+Na]+).
The physicochemical properties of compound 32 are as follows:
1) White solid, melting point 56.9-57.6 ℃ and yield 67.4%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.52–7.55(m,3H,Ph-H),7.45–7.46(m,1H,Ph-H),7.27–7.33(m,3H,Ph-H),7.17–7.24(m,2H,Ph-H),6.36(d,J＝2.8Hz,1H,13-Ha),5.93(d,J＝2.4Hz,1H,13-Hb),5.26(d,J＝2.0Hz,1H,6-H),4.92–4.95(m,1H,8-H),4.18(d,J＝12.8Hz,1H,14-Ha),3.99(d,J＝12.8Hz,1H,14-Hb),3.84–3.95(m,2H,1-H),3.45–3.49(m,1H,7-H),2.76–2.81(m,1H,4-H),2.73(d,J＝2.8Hz,2H,9-H),2.04(s,3H,1-AcO),2.01(s,3H,6-AcO),1.36–1.42(m,1H,2-Ha),1.23–1.26(m,2H,2-Hb and 3-Ha),1.00–1.07(m,1H,3-Hb),0.88(d,J＝7.2Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.13,170.61,169.05,153.79,152.55,138.43,135.69,134.59,133.63,131.49,130.34,130.19,130.00,129.80,128.28,127.98,127.33,126.15,125.39,74.36,68.70,64.13,42.72,35.22,33.54,32.38,30.73,26.61,21.25,20.95,18.42;
3) High resolution mass spectrum characteristics of the compound:
ionization by electrospray ：m/z＝658.1759(calcd.658.1755for C33H34N3O6NaS35Cl,[M+Na]+);660.1741(calcd.660.1725for C33H34N3O6NaS37Cl,[M+Na]+).
The physicochemical properties of compound 33 are as follows:
1) White solid, melting point 65.2-65.9 deg.c, yield 48.3%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.50–7.54(m,3H,Ph-H),7.38–7.41(m,2H,Ph-H),7.25–7.28(m,2H,Ph-H),6.95–6.99(m,2H,Ph-H),6.36(d,J＝2.8Hz,1H,13-Ha),5.92(d,J＝2.4Hz,1H,13-Hb),5.25(d,J＝2.0Hz,1H,6-H),4.91–4.95(m,1H,8-H),4.16(d,J＝12.8Hz,1H,14-Ha),3.97(d,J＝12.8Hz,1H,14-Hb),3.84–3.94(m,2H,1-H),3.45–3.48(m,1H,7-H),2.75–2.80(m,1H,4-H),2.73(d,J＝2.8Hz,2H,9-H),2.04(s,3H,1-AcO),2.00(s,3H,6-AcO),1.35–1.40(m,1H,2-Ha),1.21–1.25(m,2H,2-Hb and 3-Ha),1.00–1.07(m,1H,3-Hb),0.87(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.12,170.61,169.06,164.79,162.29,154.24,152.09,138.33,135.70,133.84,131.56,130.35,130.27,130.19,130.12,127.38,125.36,115.91,115.69,74.36,68.70,64.14,42.71,35.23,33.52,32.38,30.73,26.61,21.26,20.95,18.42;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 642.2054 (calcd.642.2050for C 33H34N3O6FNaS,[M+Na]+).
The physicochemical properties of compound 34 are as follows:
1) White solid, melting point 145.1-146.1 ℃ and yield 50.1%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.50–7.54(m,3H,Ph-H),7.42(t,J＝2.0Hz,1H,Ph-H),7.40(t,J＝2.0Hz,1H,Ph-H),7.25–7.27(m,4H,Ph-H),6.35(d,J＝2.4Hz,1H,13-Ha),5.92(d,J＝2.4Hz,1H,13-Hb),5.25(d,J＝2.0Hz,1H,6-H),4.91–4.95(m,1H,8-H),4.16(d,J＝12.4Hz,1H,14-Ha),3.83–3.97(m,3H,14-Hb and1-H),3.45–3.48(m,1H,7-H),2.75–2.82(m,1H,4-H),2.72(d,J＝2.8Hz,2H,9-H),2.04(s,3H,1-AcO),2.00(s,3H,6-AcO),1.34–1.42(m,1H,2-Ha),1.22–1.25(m,2H,2-Hband 3-Ha),0.99–1.07(m,1H,3-Hb),0.87(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.15,170.64,169.08,154.31,152.35,138.31,135.78,133.96,131.86,131.68,130.19,129.60,127.40,125.60,125.37,124.37,74.40,68.78,64.17,42.78,35.27,33.58,32.43,30.80,26.67,21.29,20.99,18.45;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝702.1243(calcd.702.1249for C33H34N3O6NaS79Br,[M+Na]+);704.1237(calcd.704.1229for C33H34N3O6NaS81Br,[M+Na]+).
The physicochemical properties of compound 35 are as follows:
1) Yellow solid with melting point of 87.7-88.6 ℃ and yield of 23.3%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝8.14(t,J＝2.0Hz,1H,Ph-H),8.12(t,J＝2.0Hz,1H,Ph-H),7.54–7.61(m,5H,Ph-H),7.30–7.33(m,2H,Ph-H),6.35(d,J＝2.4Hz,1H,13-Ha),5.92(d,J＝2.4Hz,1H,13-Hb),5.27(d,J＝2.0Hz,1H,6-H),4.91–4.95(m,1H,8-H),4.10(s,2H,14-H),3.87–3.99(m,2H,1-H),3.46–3.48(m,1H,7-H),2.68–2.85(m,3H,4-H and 9-H),2.04(s,3H,1-AcO),2.01(s,3H,6-AcO),1.41–1.46(m,1H,2-Ha),1.25–1.29(m,2H,2-Hb and 3-Ha),1.03–1.08(m,1H,3-Hb),0.90(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.11,170.58,169.02,153.49,153.17,148.19,138.68,135.67,133.61,132.64,131.33,130.57,130.40,128.73,127.29,125.38,123.77,74.30,68.71,64.16,42.73,34.82,33.53,32.25,30.72,26.64,21.24,20.95,18.36;
3) High resolution mass spectrum characteristics of the compound:
Electrospray ionization is adopted: m/z= 669.1994 (calcd.669.1995 for C 33H34N4O8NaS,[M+Na]+).
The physicochemical properties of compound 36 are as follows:
1) Pale yellow gummy liquid with a yield of 51.7%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝8.00–8.02(m,2H,Ph-H),7.50–7.53(m,3H,Ph-H),6.46(d,J＝2.8Hz,1H,13-Ha),6.11(d,J＝2.4Hz,1H,13-Hb),5.25(d,J＝1.2Hz,1H,6-H),5.15(dd,J＝1.6,7.6Hz,1H,8-H),4.97(d,J＝1.6Hz,1H,9-H),4.27(d,J＝12.8Hz,1H,14-Ha),4.22(d,J＝12.8Hz,1H,14-Hb),3.92–4.00(m,2H,1-H),3.72–3.74(m,1H,7-H),2.85–2.91(m,1H,4-H),2.11(s,3H,1-AcO),2.03(s,3H,6-AcO),1.30–1.33(m,1H,2-Ha),1.25–1.29(m,2H,2-Hb and 3-Ha),1.13–1.17(m,1H,3-Hb),0.98(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.11,170.81,167.70,166.20,163.18,144.73,135.14,131.83,131.66,126.89,126.78,123.43,77.86,68.42,63.90,41.88,41.53,34.78,33.05,30.74,26.68,21.48,20.92,17.87;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝627.0768(calcd.627.0777for C27H29N2O7NaS79Br,[M+Na]+);629.0751(calcd.629.0756for C27H29N2O7NaS81Br,[M+Na]+).
The physicochemical properties of compound 37 are as follows:
1) Pale yellow gummy liquid, yield 49.4%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.99–8.01(m,1H,Ph-H),7.88–7.91(m,1H,Ph-H),7.49–7.52(m,1H,Ph-H),7.43–7.47(m,1H,Ph-H),6.45(d,J＝1.8Hz,1H,13-Ha),6.11(d,J＝2.4Hz,1H,13-Hb),5.26(d,J＝1.6Hz,1H,6-H),5.15(dd,J＝1.6,7.6Hz,1H,8-H),4.97(d,J＝2.0Hz,1H,9-H),4.28(d,J＝13.2Hz,1H,14-Ha),4.21(d,J＝12.8Hz,1H,14-Hb),3.94–4.00(m,2H,1-H),3.71–3.74(m,1H,7-H),2.85–2.91(m,1H,4-H),2.11(s,3H,1-AcO),2.04(s,3H,6-AcO),1.48–1.54(m,1H,2-Ha),1.27–1.32(m,2H,2-Hb and 3-Ha),1.11–1.17(m,1H,3-Hb),0.98(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.11,170.80,167.67,165.03,163.69,144.90,135.24,135.10,131.86,131.50,130.46,126.92,126.75,125.04,124.84,77.84,68.40,63.89,41.79,41.51,34.77,33.01,30.71,26.68,21.48,20.93,17.85;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝661.0391(calcd.661.0387for C27H28N2O7NaS35Cl79Br,[M+Na]+);663.0384(calcd.663.0366for C27H28N2O7NaS35Cl81Br,[M+Na]+);663.0384(calcd.663.0357for C27H28N2O7NaS37Cl79Br,[M+Na]+);665.0341(calcd.665.0337for C27H28N2O7NaS37Cl81Br,[M+Na]+).
The physicochemical properties of compound 38 are as follows:
1) Pale yellow gummy liquid with a yield of 34.1%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.64(dd,J＝0.8,2.0Hz,1H,Furan-H),7.14(dd,J＝0.8,3.6Hz,1H,Furan-H),6.60(dd,J＝2.0,3.6Hz,1H,Furan-H),6.45(d,J＝2.4Hz,1H,13-Ha),6.11(d,J＝2.0Hz,1H,13-Hb),5.25(d,J＝1.2Hz,1H,6-H),5.14(dd,J＝1.6,7.6Hz,1H,8-H),4.95(d,J＝2.0Hz,1H,9-H),4.25(d,J＝12.8,Hz,1H,14-Ha),4.20(d,J＝12.8Hz,1H,14-Hb),3.92–4.01(m,2H,1-H),3.70–3.74(m,1H,7-H),2.83–2.90(m,1H,4-H),2.11(s,3H,1-AcO),2.04(s,3H,6-AcO),1.49–1.55(m,1H,2-Ha),1.25–1.32(m,2H,2-Hb and 3-Ha),1.10–1.17(m,1H,3-Hb),0.98(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.09,170.79,167.65,162.60,158.89,145.82,144.93,138.91,135.11,131.43,126.89,114.24,112.19,77.84,68.41,63.87,41.80,41.51,34.76,33.15,30.72,26.66,21.47,20.92,17.84;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝617.0567(calcd.617.0569for C25H27N2O8NaS79Br,[M+Na]+);619.0551(calcd.619.0549for C25H27N2O8NaS81Br,[M+Na]+).
The physicochemical properties of compound 39 are as follows:
1) Pale yellow gummy liquid with a yield of 68.6%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.73(dd,J＝1.2,3.6Hz,1H,Thiophene-H),7.56(dd,J＝1.2,5.2Hz,1H,Thiophene-H),7.17(dd,J＝3.6,4.8Hz,1H,Thiophene-H),6.46(d,J＝2.8Hz,1H,13-Ha),6.11(d,J＝2.4Hz,1H,13-Hb),5.25(d,J＝1.2Hz,1H,6-H),5.15(dd,J＝1.6,7.6Hz,1H,8-H),4.96(d,J＝1.6Hz,1H,9-H),4.25(d,J＝12.8Hz,1H,14-Ha),4.20(d,J＝12.8Hz,1H,14-Hb),3.91–4.01(m,2H,1-H),3.71–3.74(m,1H,7-H),2.84–2.89(m,1H,4-H),2.11(s,3H,1-AcO),2.04(s,3H,6-AcO),1.48–1.55(m,1H,2-Ha),1.25–1.30(m,2H,2-Hb and 3-Ha),1.10–1.17(m,1H,3-Hb),0.98(d,J＝7.2Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.09,170.79,167.67,162.53,162.36,144.79,135.13,131.59,130.27,129.91,128.19,126.88,124.60,77.85,68.41,63.88,41.85,41.52,34.77,33.11,30.74,26.68,21.48,20.93,17.86;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝633.0345(calcd.633.0341for C25H27N2O7NaS2 79Br,[M+Na]+);635.0331(calcd.635.0320for C25H27N2O7NaS2 81Br,[M+Na]+).
The physicochemical properties of compound 40 are as follows:
1) Pale yellow gummy liquid with a yield of 29.8%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝8.82(d,J＝3.6Hz,1H,Py-H),8.24(d,J＝7.6Hz,1H,Py-H),7.97(t,J＝7.2Hz,1H,Py-H),7.51–7.54(m,1H,Py-H),6.45(d,J＝2.8Hz,1H,13-Ha),6.11(d,J＝2.0Hz,1H,13-Hb),5.25(d,J＝0.8Hz,1H,6-H),5.14(dd,J＝1.6,8.0Hz,1H,8-H),4.99(d,J＝1.6Hz,1H,9-H),4.30(d,J＝13.2Hz,1H,14-Ha),4.26(d,J＝13.2Hz,1H,14-Hb),3.93–4.01(m,2H,1-H),3.71–3.73(m,1H,7-H),2.88–2.93(m,1H,4-H),2.11(s,3H,1-AcO),2.04(s,3H,6-AcO),1.51–1.57(m,1H,2-Ha),1.29–1.33(m,2H,2-Hb and 3-Ha),1.13–1.20(m,1H,3-Hb),0.98(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.15,170.83,167.64,164.89,164.78,149.90,145.03,142.56,138.00,135.15,131.47,126.86,126.14,123.16,77.88,68.44,63.92,41.87,41.50,34.80,33.13,30.71,26.68,21.50,20.96,17.85;
3) High resolution mass spectrum characteristics of the compound:
ionization by electrospray ：m/z＝628.0732(calcd.628.0729for C26H28N3O7NaS79Br,[M+Na]+);630.0717(calcd.630.0709for C26H28N3O7NaS81Br,[M+Na]+).
The physicochemical properties of compound 41 are as follows:
1) White solid with melting point 67.0-67.8 ℃ and yield 45.2%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.50–7.51(m,3H,Ph-H),7.41–7.43(m,2H,Ph-H),7.27–7.36(m,5H,Ph-H),6.42(d,J＝2.4Hz,1H,13-Ha),6.08(d,J＝2.0Hz,1H,13-Hb),5.22(s,1H,6-H),5.08(d,J＝6.8Hz,1H,8-H),4.95(s,1H,9-H),4.32(d,J＝13.2Hz,1H,14-Ha),4.14(d,J＝12.8Hz,1H,14-Hb),3.84–3.96(m,2H,1-H),3.64–3.69(m,1H,7-H),2.87–2.94(m,1H,4-H),2.09(s,3H,1-AcO),1.98(s,3H,6-AcO),1.42–1.46(m,1H,2-Ha),1.27–1.34(m,2H,2-Hb and 3-Ha),1.12–1.14(m,1H,3-Hb),0.94(d,J＝7.2Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.04,170.86,143.74,135.33,133.91,132.76,130.08,129.86,129.72,128.51,128.30,128.25,127.41,126.62,77.86,68.59,64.06,42.04,41.55,34.52,32.46,30.70,29.70,26.54,21.49,20.89,17.91;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝702.1242(calcd.702.1249for C33H34N3O6NaS79Br,[M+Na]+);704.1229(calcd.704.1229for C33H34N3O6NaS81Br,[M+Na]+).
The physicochemical properties of compound 42 are as follows:
1) White solid, melting point 58.1-58.9 deg.c, yield 66.4%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.49–7.51(m,3H,Ph-H),7.34–7.35(m,1H,Ph-H),7.31–7.32(m,1H,Ph-H),7.24–7.27(m,2H,Ph-H),6.79–6.80(m,1H,Ph-H),6.76–6.78(m,1H,Ph-H),6.41(d,J＝2.4Hz,1H,13-Ha),6.08(d,J＝2.4Hz,1H,13-Hb),5.21(d,J＝0.8Hz,1H,6-H),5.08(dd,J＝1.6,8.0Hz,1H,8-H),4.94(d,J＝2.0Hz,1H,9-H),4.29(d,J＝13.2Hz,1H,14-Ha),4.12(d,J＝13.2Hz,1H,14-Hb),3.83–3.96(m,2H,1-H),3.77(s,3H,-OMe),3.66–3.69(m,1H,7-H),2.85–2.90(m,1H,4-H),2.09(s,3H,1-AcO),1.98(s,3H,6-AcO),1.38–1.44(m,1H,2-Ha),1.24–1.27(m,2H,2-Hband 3-Ha),1.08–1.14(m,1H,3-Hb),0.93(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.05,170.87,167.80,160.70,155.25,151.00,143.56,135.34,134.10,132.88,130.05,129.97,129.72,127.47,126.60,118.93,113.95,77.85,68.57,64.05,55.26,42.09,41.54,34.50,32.49,30.70,26.53,21.49,20.90,17.91;
3) High resolution mass spectrum characteristics of the compound:
ionization by electrospray ：m/z＝710.1544(calcd.710.1536for C34H37N3O7S79Br,[M+H]+);712.1534(calcd.712.1515for C34H37N3O7S81Br,[M+H]+).
The physicochemical properties of compound 43 are as follows:
1) White solid, melting point of 51.8-52.5 ℃ and yield of 68.7%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.51–7.55(m,3H,Ph-H),7.47–7.48(m,1H,Ph-H),7.29–7.32(m,1H,Ph-H),7.26–7.28(m,1H,Ph-H),7.26(s,1H,Ph-H),7.21–7.23(m,1H,Ph-H),7.16–7.20(m,1H,Ph-H),6.41(d,J＝2.4Hz,1H,13-Ha),6.08(d,J＝2.4Hz,1H,13-Hb),5.22(d,J＝1.2Hz,1H,6-H),5.09(dd,J＝2.0,8.0Hz,1H,8-H),4.97(d,J＝1.6Hz,1H,9-H),4.33(d,J＝13.2Hz,1H,14-Ha),4.13(d,J＝13.2Hz,1H,14-Hb),3.84–3.96(m,2H,14-H),3.66–3.70(m,1H,7-H),2.87–2.92(m,1H,4-H),2.09(s,3H,1-AcO),1.99(s,3H,6-AcO),1.38–1.46(m,1H,2-Ha),1.24–1.27(m,2H,2-Hband 3-Ha),1.07–1.14(m,1H,3-Hb),0.94(d,J＝7.2Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.06,170.86,167.78,154.03,151.94,143.83,135.24,134.53,133.57,132.64,130.33,130.22,129.89,129.73,128.31,128.17,127.31,126.68,126.14,77.83,68.52,64.04,41.92,41.48,34.47,32.30,30.64,26.51,21.50,20.92,17.88;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝714.1042(calcd.714.1040for C33H34N3O6S35Cl79Br,[M+H]+;716.1049(calcd.716.1020for C33H34N3O6S35Cl81Br,[M+H]+).
The physicochemical properties of compound 44 are as follows:
1) White solid with melting point 67.5-68.2 ℃ and yield 32.5%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝7.50–7.54(m,3H,Ph-H),7.39–7.42(m,2H,Ph-H),7.25–7.29(m,4H,Ph-H),6.40(d,J＝2.4Hz,1H,13-Ha),6.07(d,J＝2.0Hz,1H,13-Hb),5.22(d,J＝0.8Hz,1H,6-H),5.08(dd,J＝1.6,7.6Hz,1H,8-H),4.97(d,J＝1.6Hz,1H,9-H),4.32(d,J＝13.2Hz,1H,14-Ha),4.11(d,J＝13.2Hz,1H,14-Hb),3.84–3.97(m,2H,1-H),3.67–3.69(m,1H,7-H),2.87–2.92(m,1H,4-H),2.09(s,3H,1-AcO),1.99(s,3H,6-AcO),1.38–1.46(m,1H,2-Ha),1.25–1.27(m,2H,2-Hband 3-Ha),1.09–1.15(m,1H,3-Hb),0.94(d,J＝7.2Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.03,170.84,167.77,154.43,151.76,143.79,135.26,133.72,132.69,131.78,130.24,130.21,129.64,127.33,126.63,125.50,124.34,77.83,68.54,64.05,41.93,41.49,34.47,32.29,30.65,26.52,21.49,20.91,17.86;
3) High resolution mass spectrum characteristics of the compound:
Ionization by electrospray ：m/z＝780.0359(calcd.780.0355for C33H33N3O6S79Br2Na,[M+Na]+);782.0394(calcd.782.0334for C33H33N3O6S79Br81BrNa,[M+Na]+);784.0335(calcd.784.0314for C33H33N3O6S81Br2Na,[M+Na]+).
The physicochemical properties of compound 45 are as follows:
1) White solid with a melting point of 57.2-58.1 ℃ and a yield of 25.5%;
2) Nuclear magnetic resonance spectrum characteristics of the compound:
Deuterated chloroform is used as solvent, TMS is used as internal standard, wherein each peak is attributed to ：–1H NMR(400MHz,CDCl3):δ＝8.12–8.14(m,2H,Ph-H),7.59–7.61(m,2H,Ph-H),7.53–7.57(m,3H,Ph-H),7.31(d,J＝1.6Hz,1H,Ph-H),7.29(d,J＝2.0Hz,1H,Ph-H),6.40(d,J＝2.4Hz,1H,13-Ha),6.07(d,J＝2.4Hz,1H,13-Hb),5.24(d,J＝0.8Hz,1H,6-H),5.08(dd,J＝1.6,7.6Hz,1H,8-H),5.02(d,J＝1.6Hz,1H,9-H),4.39(d,J＝13.6Hz,1H,14-Ha),4.10(d,J＝13.6Hz,1H,14-Hb),3.87–3.99(m,2H,1-H),3.64–3.69(m,1H,7-H),2.90–2.95(m,1H,4-H),2.10(s,3H,1-AcO),2.00(s,3H,6-AcO),1.44–1.51(m,1H,2-Ha),1.27–1.31(m,2H,2-Hb and 3-Ha),1.11–1.17(m,1H,3-Hb),0.95(d,J＝6.8Hz,3H,15-H).–13C NMR(100MHz,CDCl3):δ＝171.06,170.83,167.79,153.35,152.72,148.22,144.15,135.17,133.45,132.58,132.42,130.63,130.45,128.85,127.26,126.70,123.74,77.83,68.52,64.10,41.69,41.44,34.45,32.08,30.61,26.54,21.49,20.94,17.81;
3) High resolution mass spectrum characteristics of the compound:
ionization by electrospray ：m/z＝747.1091(calcd.747.1100for C33H33N4O8NaS79Br,[M+Na]+);749.1079(calcd.749.1080for C33H33N4O8NaS81Br,[M+Na]+).
Example 2
Antibacterial Activity assay of the invention:
this example shows the antibacterial activity test of 1-oxo-acetylinula lactone derivatives (1-45) containing 1,3, 4-oxadiazole/1, 2, 4-triazole heterocyclic structures prepared in example 1:
1. Test plant pathogenic fungi: tomato early blight (ALTERNARIA SOLANI), fusarium solani (Fusarium solani), cucumber anthracnose (Colletotrichum orbiculare), pepper Fusarium wilt (Fusarium oxysporum), wheat red fungus (Fusarium graminearum), tomato gray fungus (Botrytis cinerea) and apple tree rot (Cytospora mandshurica).
2. Test sample and reagent:
sample supply: 1-45 of 1-oxo-acetylinula lactone derivative containing 1,3, 4-oxadiazole/1, 2, 4-triazole heterocyclic structure prepared in example 1;
Control agent: raw materials of 1-O-acetyl inula lactone (1-O-acetylbritannilactone), 99% of hymexazol raw material and 98% of difenoconazole raw material;
Solvent: DMSO (dimethyl sulfoxide, chromatographic purity), acetone (analytical purity), and tween-80 (superior purity) as emulsifier.
3. Antibacterial activity test method:
(1) The inhibitory effect of the derivatives 1 to 45 prepared in example 1 on the hypha growth of seven plant pathogenic fungi was tested by using a hypha growth rate assay: all samples were dissolved in acetone and mixed with the melted PDA medium, and poured into sterile dishes, each dish was about 15mL, to prepare a drug-containing medium with a concentration of 100. Mu.g/mL (the content of acetone in the drug-containing medium was not more than 0.5%, v/v). After the culture medium is cooled and solidified, the test strain which is activated in advance is beaten into a bacterial cake with the diameter of 4mm along the edge of a bacterial colony, the bacterial cake is inoculated at the right center of the drug-containing culture medium, each drug is repeated for 3 times, and a blank control test without the drug is arranged. Culturing at a proper temperature until the colony diameter of the blank control group reaches 2/3 of the diameter of the culture dish, measuring the colony diameters of each treatment group and the control group by adopting a crisscross method, calculating the hypha growth inhibition rate of each medicament treatment group according to a formula-1, calculating corresponding standard deviation and the like. The measurement results are shown in Table-1.
Hypha growth inhibition ratio = (average colony diameter of control group-average colony diameter of treatment group)/(average colony diameter of control group-4 mm) ×100% (formula-1)
Inhibitory Activity of surface-1 1-oxygen-acetyl inula lactone compounds (derivatives 1-45) on growth of seven plant pathogenic fungi hypha
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From Table-1, the following conclusions can be drawn: at a test concentration of 100 mug/mL, most of the derivatives show different degrees of hypha growth inhibition effects on the tested plant pathogenic fungi; wherein 10 derivatives (2, 7, 13, 15, 24, 30, 37, 39, 42 and 45) have higher inhibitory activity on tomato early blight bacteria than parent 1-oxo-acetyl inula lactone; the inhibition effect of 14 derivatives (1, 2, 4, 6, 7, 9, 13, 14, 15, 30, 38, 40, 41 and 44) on Fusarium solani is superior to that of the raw material 1-oxo-acetylinula lactone; 26 derivatives (1, 2, 4, 7, 8, 9, 12, 13, 14, 15, 19, 21, 22, 24, 25, 26, 28, 30, 31, 36, 37, 38, 39, 41, 44 and 45) have higher in-vitro inhibition activity on cucumber anthracnose germs, and the inhibition rate exceeds that of 1-oxo-acetyl inula lactone; almost all tested derivatives (except derivatives 5, 8, 17, 18 and 20) had higher inhibition of pepper fusarium wilt than 1-oxo-acetylinula lactone; all tested derivatives except 28 and 35 showed higher activity against gibberella wheat than the parent 1-oxo-acetylinula lactone; the inhibition rate of the derivatives 2, 4, 9, 13, 15, 16, 20, 23, 28, 33, 34, 36, 40 and 44 on botrytis cinerea is higher than that of 1-oxo-acetyl inula lactone; the antibacterial activity of the derivatives 2, 15 and 37 on apple tree canker is superior to that of parent 1-oxo-acetyl inula lactone.
In conclusion, most of the prepared derivatives have higher inhibition activity on cucumber anthracnose, pepper fusarium wilt and wheat gibberella than raw material 1-oxo-acetylinula lactone, which shows that the introduction of 1,3, 4-oxadiazole or 1,2, 4-triazole heterocyclic structure on the molecular skeleton of 1-oxo-acetylinula lactone is helpful for improving the antibacterial activity of the substances. The derivative 2 has excellent inhibition activity on 7 fungi to be tested, especially has the inhibition rate of 100% on wheat gibberella, tomato botrytis cinerea and apple tree canker, and far exceeds the commercial positive control medicament hymexazol, so that the derivative has high-efficiency and broad-spectrum fungus hypha inhibition activity and has great application potential.
(2) The germination inhibition activity of 1-oxo-acetylinula lactone derivatives (1-45) containing 1,3, 4-oxadiazole/1, 2, 4-triazole heterocyclic structures prepared in example 1 on spores of four plant pathogenic fungi was tested by spore germination method: a. preparation of spore suspension: culturing pathogenic bacteria on PDA culture medium at 25+ -1deg.C for 2 weeks, scraping colony with scraper, washing with sterile water, filtering with double-layer gauze to remove mycelium and culture medium, washing with sterile water repeatedly for 3 times, and diluting with sterile water to required spore concentration (about 20-40 spores per field under 100 times microscope); b. and (3) preparation of a medicament: dissolving a sample to be tested in a certain amount of DMSO, diluting with 0.1% Tween-80 sterile aqueous solution to prepare 1mg/mL stock solution, and setting 5-7 series mass concentrations according to the activity of the medicament, wherein the final content of the organic solvent is not more than 2% (v/v); c. and (3) medicament treatment: the prepared sample solution and spore suspension are uniformly mixed in equal volume to obtain the required final concentration. As a control, 2% DMSO was added to a 0.1% Tween-80 sterile aqueous solution. The mixed liquid is sucked by a microsampler and is dropped into a concave glass slide, placed in a culture dish with shallow water, capped and placed in an incubator with proper temperature for culture. The germination of spores on the slides was observed under a microscope. When the spore tube after the spore germination is larger than the short diameter of the spore, namely the germination, when the spore germination rate of the blank control is larger than 90%, observing and calculating the spore germination rate of each treatment group (formula-2), simultaneously calculating the corrected spore germination inhibition rate of each treatment group by adopting formula-3, and solving the concentration in inhibition of each compound, the confidence interval of 95%, and the like, wherein the measurement result is shown in Table-2.
Spore germination rate = number of germinated spores/total number of statistical spores x 100% (formula-2);
corrected spore germination inhibition = (average spore germination rate of control group-average spore germination rate of treated group)/average spore germination rate of control group x 100% (formula-3).
Germination inhibition of four plant pathogenic fungi spores by epi-2 1-oxy-acetyl inula lactone compounds (derivatives 1-45)
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As can be seen from the data in table-2: the raw material 1-oxo-acetyl inula lactone has larger concentration in inhibiting 4 test fungal spores and has general inhibition activity. The germination inhibition effect of most of the tested derivatives on fungus spores is higher than that of parent 1-oxo-acetylinula lactone, while the germination inhibition activity of the derivative 2 on botrytis cinerea spores is most outstanding, the concentration in inhibition reaches 47.69 mug/mL, the inhibition activity is far higher than that of 1-oxo-acetylinula lactone and a positive control medicament difenoconazole, and the derivatives have the potential of being used as potential botrytis cinerea spore germination inhibitors.

Claims (3)

  1. The 1-oxo-acetyl inula lactone derivative is characterized by having a structure shown in a formula I or a pharmaceutically acceptable salt of the structure shown in the formula I:
    ；
    （Ⅰ）
    In formula i, R 1、 R2 and R 3 are any one of the following combinations:
    （7）R1=R-b,R2=H,R3=H;（13）R1=R-h,R2=H,R3=H；
    （21）R1=H,R2=R-a,R3=H;（22）R1=H,R2=R-b,R3=H；
    （23）R1=H,R2=R-d,R3=H;（24）R1=H,R2=R-f,R3=H；
    （25）R1=H,R2=R-g,R3=H;（26）R1=H,R2=R-h,R3=H；
    （28）R1=H,R2=R-j,R3=H;（30）R1=H,R2=R-l,R3=H；
    （33）R1=H,R2=R-o,R3=H;（34）R1=H,R2=R-p,R3=H；
    （37）R1=H,R2=R-d,R3=Br;（38）R1=H,R2=R-h,R3=Br；
    （39）R1=H,R2=R-i,R3=Br;（40）R1=H,R2=R-j,R3=Br；
    Wherein R-a, R-b, R-d, R-f, R-g, R-h, R-i, R-j, R-l, R-o to R-p are each the following groups:
    。
  2. 2. Use of the derivative according to claim 1 for inhibiting the species Fusarium solani (ALTERNARIA SOLANI), fusarium solani (Fusarium solani), cucumber anthracnose (Colletotrichum orbiculare), pepper Fusarium wilt (Fusarium oxysporum), botrytis cinerea (Botrytis cinerea) and apple tree rot (Cytospora mandshurica).
  3. 3. A preparation comprising the derivative according to claim 1.
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CN101518266A (en) * 2008-02-27 2009-09-02 河北省农林科学院植物保护研究所 Preparation method and application of inula japonica extract and combination thereof
CN106806364A (en) * 2015-12-02 2017-06-09 复旦大学 Application of the diacetyl Britanin in antineoplastic sensitizer is prepared

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两种天然产物的衍生合成及杀虫抗菌活性的研究;张菲宇;《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑 (月刊)》;20140215(第02期);第B016-186页 *

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