Zeylenone and derivative thereof, and preparation method and application thereof

A technology of sanhoprolene and derivatives, which is applied in the field of medicinal chemistry, can solve the problems of unsolved sources of sanhoprolone and inability to meet a large amount of demand for compounds, and achieves the effects of efficient preparation, high sensitivity and good selectivity.

Active Publication Date: 2021-02-26
INST OF MEDICINAL PLANT DEV CHINESE ACADEMY OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] In view of this, the object of the present invention is to propose a kind of sanshocenone and its derivatives, its preparation method and application, to solve the source of sanshocenone Unresolved, inability to meet the high demand for compounds for in vivo experiments

Method used

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  • Zeylenone and derivative thereof, and preparation method and application thereof
  • Zeylenone and derivative thereof, and preparation method and application thereof
  • Zeylenone and derivative thereof, and preparation method and application thereof

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preparation example Construction

[0047] The present invention also provides a kind of preparation method of sanspotenone and derivatives thereof as described above, comprising:

[0048] providing a compound of formula (V);

[0049]

[0050] The compound with the structure of formula (V) is sequentially subjected to acetone acetal protection of cis-dihydroxyl group, benzoylation protection reaction and deprotection reaction with dilute hydrochloric acid to obtain the compound with structure of formula (I);

[0051] or

[0052] The compound with the structure of formula (V) is sequentially subjected to acetone acetal protection and benzoylation protection reactions of the cis-dihydroxyl group to obtain the compound with the structure of formula (II).

[0053] The preparation method of the compound of formula (V) structure provided by the present invention can specifically be:

[0054]performing an asymmetric dihydroxylation reaction on the first reactant with an asymmetric dihydroxylating agent to obtain a...

Embodiment 1

[0095] The synthesis of embodiment 1 compound QA2-1

[0096]Quinic acid (5.5g, 23.6mmol) was dissolved in 100mL of anhydrous methanol, and 2,3-butanedione (4.53mL, 86mmol) and trimethyl orthoformate (12.89mL, 118mmol) were added under stirring, ( ±) camphorsulfonic acid (4.53mL, 86mmol), reflux at 70°C for 10h. Add 5 mL of triethylamine to quench the reaction, and concentrate to obtain a crude product. Purified by silica gel column chromatography (dichloromethane-methanol, 30:1-20:1) to obtain compound QA2-1 (6.69 g), a white powder, with a yield of 90%.

[0097] 1 HNMR (600MHz, MeOD) δ4.31 (ddd, J = 12.0, 10.2, 4.5Hz, 1H), 4.12-4.10 (m, 1H), 3.77 (s, 3H), 3.55 (dd, J = 10.2, 2.9Hz ,1H),3.28(s,3H),3.28(s,3H),2.08-2.04(m,3H),1.87(t,J=12.5Hz,1H),1.34(s,3H),1.29(s, 3H). 13 CNMR (150MHz, MeOD) δ173.97(s), 99.58(s), 99.17(s), 75.34(s), 72.62(s), 68.15(s), 62.11(s), 51.23(s), 46.38( s),37.78(s),36.98(s),16.35(s),16.25(s).HRMS(ESI):m / z calcd.C 13 h 21 o 7 [M+H] + :289.1287,...

Embodiment 2

[0098] The synthesis of embodiment 2 compound QA2-2 and QA2-3

[0099] Compound QA2-1 (6.69g, 21.2mmol) was dissolved in 100mL of anhydrous methanol, sodium borohydride (1.9g, 50mmol) was added in batches under stirring, and the reaction was vigorously stirred at 0°C for 2h. TLC detected the completion of the reaction, added 5 mL of water to quench, added 5 mL of dilute hydrochloric acid to stand still, and concentrated to obtain a crude product. Purification by silica gel column chromatography (dichloromethane-methanol, 10:1) gave crude compound QA2-2 (5.4 g), a white powder, with a yield of 87%, which was directly used in the next step without purification.

[0100] In the reaction flask containing the crude product of QA2-2 (5.4g, 18.44mmol), add phosphate buffer (0.2M, ph=7), and add sodium periodate in batches under ice cooling. React at room temperature, TLC detects that the reaction is complete, add 100 mL×3 dichloromethane for extraction, and concentrate to obtain a c...

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Abstract

The invention provides application of zeylenone and derivatives thereof in preparation of anti-tumor drugs. The zeylenone is of a (+)-zeylenone configuration, and the molecular formula is shown as a formula (I). The derivative has a structure shown as a formula (II). The invention also provides a preparation method of zeylenone and the derivative thereof. The invention also provides application ofthe zeylenone and the derivative thereof or the zeylenone and the derivative thereof prepared by the preparation method of any one of the zeylenone and the derivative thereof in preparation of anti-tumor drugs. The tumor is selected from at least one of human brain glioma, human nasopharyngeal carcinoma, human liver cancer, human lung cancer, human neuroglioblastoma, human prostate cancer and mouse pancreatic cancer. The zeylenone and the derivative thereof are high in sensitivity and good in selectivity, and can be used for preparing anti-tumor drugs.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a sanshocenone and its derivatives, a preparation method and application thereof. Background technique [0002] Sansoperenone is a cyclohexenone compound. Sanshoolenone extracted from Uvariagrandiflora Roxb. is in the (-)-zeylenone configuration, the CAS number is 193410-84-3, and the molecular formula is C 21 h 18 o 7 , the structural formula is [0003] Pharmacological activity studies have shown that (-)-zeylenone has good cytotoxic activity against a variety of tumor cells, and has the potential to be developed into a new drug as a lead compound. However, the problem of the source of sanspotenone has not been solved at present, which cannot meet the large demand for compounds in vivo experiments. Contents of the invention [0004] In view of this, the object of the present invention is to propose a kind of sanspotenone and its derivatives, its preparation...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07C69/78C07D317/46C07C67/29C07D319/20C07D493/04A61K31/235A61K31/36A61P35/00
CPCC07C69/78C07D317/46C07C67/29C07D319/20C07D493/04A61P35/00C07C2601/16Y02P20/55
Inventor 许旭东孙忠浩曹丽田瑜杨淑贤单宇
Owner INST OF MEDICINAL PLANT DEV CHINESE ACADEMY OF MEDICAL SCI
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