Novel 16-membered macrolide compound as well as preparation method and application thereof

Abstract

The invention provides and relates to a novel 16-membered macrolide compound 27-(S)-hydroproxy tenvermectin B, a preparation method thereof and application of the novel 16-membered macrolide compound 27-(S)-hydroproxy tenvermectin B in preparation of drugs for preventing and treating agriculture and forestry mites. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the field of pesticides, and specifically relates to a preparation method of a novel 16-membered macrolide compound 27-(S)-hydroperoxy tebuconazole B and an application of the novel compound in the preparation of a drug for preventing and controlling agricultural and forestry harmful mites. Background Art

[0002] Tenvermectin A and B (structure as shown below) are new low-toxic and highly effective insecticidal polyketide compounds obtained by Chinese scientists through genetic engineering technology by hybridizing the structural characteristics of avermectin and milbemycin. They have the potential to be developed into new insecticides. Currently, the single component of Tenvermectin B is being developed into a new type of pesticide and new veterinary drug.

[0003]

[0004] The invention uses avermectin B as a starting material and prepares a novel 16-membered macrolide compound 27-(S)-hydroperoxy avermectin B by light irradiation. The acaricidal activity of the compound is superior to that of avermectin B and avermectin B1, and the compound has the potential to be developed into a novel acaricide. Summary of the invention

[0005] In order to make up for the above deficiencies, the present invention provides a novel 16-membered macrolide compound that overcomes the above technical problems or at least partially solves the above problems, and a preparation method and use thereof.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] The present invention relates to a novel 16-membered macrolide compound, wherein the compound has a chemical structure as shown in the following formula I:

[0008]

[0009] A method for preparing the compound I according to claim 1, the method comprising using tianweimectin B as a raw material and reacting under light conditions to produce it.

[0010] Furthermore, the method comprises the following steps:

[0011] (1) dissolving the tianweimectin B raw material in an organic solvent;

[0012] (2) transferring the solution of step (1) into a UV light box for irradiation;

[0013] (3) The solution obtained from the reaction in step (2) is subjected to column chromatography to obtain 27-(S)-hydroperoxy cypermethrin B.

[0014] Furthermore, the organic solvent in step (1) is a medium-strong polar organic solvent.

[0015] Furthermore, the ultraviolet light irradiation condition is irradiation at 700W / m2 for more than 24 hours.

[0016] Furthermore, the column chromatography in step (3) is reverse phase silica gel column chromatography.

[0017] Furthermore, the reverse phase chromatography column used in the reverse phase silica gel column chromatography in step (3) is a reverse C18 column, and the elution solvent used in the reverse phase column chromatography is selected from an aqueous solution of an organic solvent such as acetonitrile, methanol, or acetonitrile.

[0018] Furthermore, the organic solvent is selected from one or more of acetonitrile, methanol, and acetonitrile solvents, and the volume ratio of the organic solvent to water in the aqueous solution of the organic solvent is 50:70-100:0.

[0019] The present invention further provides a pharmaceutical composition comprising the above-mentioned compound and one or more conventional carriers and / or diluents.

[0020] The present invention further provides the use of the above-mentioned compound I in the preparation of a drug for controlling pest mites of crops. DETAILED DESCRIPTION

[0021] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0022] Example 1 Synthesis of Compound 1

[0023] 200 mg of tianweimectin B was dissolved in 20 mL of methanol and then placed in a UV light box (700 W / m 2 ) for 48 hours. After irradiation, the sample was subjected to column chromatography to obtain compound 1. The conditions for preparative column chromatography were as follows:

[0024] Chromatographic column: ODS, 20 mm × 250 mm;

[0025] The mobile phase was: acetonitrile: water = 65:35;

[0026] Detection wavelength: 240nm;

[0027] Flow rate: 20ml / min;

[0028] Column temperature: room temperature;

[0029] Retention time (weight): 42-44 mins (21 mg).

[0030] The structure of compound formula I is as follows:

[0031]

[0032] Example 2 Structural Identification of Compound 1

[0033] Compound 1 obtained in Example 1, (c0.36,EtOH);UV(EtOH)λ max (logε)247(4.21)nm; IR(KBr)ν max 3455,2930,1719,1449,1377,1344,1300,1143,1102,1046,980,871cm -1 ; HRESIMS m / z 901.4555[M+Na] + (C 46 H 70 O 16 Na + , the calculated value is 901.4556). 1 H and 13 C NMR data are shown in Table 1. In summary, compound 1 can be identified as 27-(S)-hydroperoxytetracycline B, and its structure is as shown in the above compound formula I structure.

[0034] Table 1 NMR data of the new macrolide compound obtained in Example 1 in deuterated chloroform

[0035]

[0036]

[0037] Example 3 Biological activity of compound 1 against Tetranychus cinnabarinus

[0038] The test method refers to the literature (Huang, J.; Chen, AL; Zhang, H.; Yu, Z.; Li, MH; Li, N.; Lin, JT; Bai, H.; Wang, JD; Zheng, YGGene replacement for the generation of designed novel avermectin derivatives with enhanced acaricidal and nematicidal activities. Appl. Environ. Microbiol. 2015, 81, 5326–5334.), and the experimental results are shown in Table 2.

[0039] Table 2: Activity of compound 1 against Tetranychus cinnabarinus

[0040] Compound Toxicity regression equation (y=) <![CDATA[LC 50 (mg / L)]]> Compound 1 6.4371+0.9969X 0.0113 Tianweimectin B 6.7656+1.2681X 0.0212 Avermectin B1 6.2765+1.1340X 0.0248

Claims

1. A novel 16-membered macrolide compound, characterized in that: The compound has a chemical structure as shown in the following formula I:

2. A method for preparing the compound I according to claim 1, characterized in that: The method comprises the steps of using tianweimectin B as a raw material and reacting it under light conditions.

3. The method according to claim 2, characterized in that: The method comprises the following steps: (1) dissolving the tianweimectin B raw material in an organic solvent; (2) transferring the solution of step (1) into a UV light box for irradiation; (3) The solution obtained from the reaction in step (2) is subjected to column chromatography to obtain 27-(S)-hydroperoxy cypermethrin B.

4. The method according to claim 3, characterized in that: The organic solvent described in step (1) is a medium-strong polar organic solvent.

5. The method according to claim 3, characterized in that: The ultraviolet light irradiation condition is irradiation at 700W / m2 for more than 24 hours.

6. The method according to claim 3, characterized in that: The column chromatography in step (3) is reverse phase silica gel column chromatography.

7. The method according to claim 6, characterized in that: The reverse phase chromatography column used in the reverse phase silica gel column chromatography in step (3) is a reverse C18 column, and the elution solvent used in the reverse phase column chromatography is selected from an aqueous solution of an organic solvent such as acetonitrile, methanol, or acetonitrile.

8. The method according to claim 7, characterized in that: The organic solvent is selected from one or more of acetonitrile, methanol, and acetonitrile solvents, and the volume ratio of the organic solvent to water in the aqueous solution of the organic solvent is 50:70-100:

0.

9. A pharmaceutical composition comprising the compound according to claim 1 and one or more conventional carriers and / or diluents.

10. Use of the compound I according to claim 1 in the preparation of a drug for controlling pests of crops.

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