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Asiatic acid derivatives, their preparation methods and their application in the preparation of antidepressants

An antidepressant and drug technology, applied in the field of natural medicinal chemistry, can solve the problems of application limitations, large adverse reactions, poor bioavailability, etc., and achieve high antidepressant activity

Active Publication Date: 2019-03-26
NAVY MEDICINE RES INST OF PLA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The application of traditional tricyclic and tetracyclic antidepressants and monoamine oxidase inhibitors is limited due to relatively large adverse reactions
[0007] After many years of research, the inventor has found that Asiatic acid has a good antidepressant effect. For example, the antidepressant effect of Asiatic acid is provided in detail in CN1256090C, but its bioavailability is poor. Asiatic acid derivatives with better bioavailability

Method used

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  • Asiatic acid derivatives, their preparation methods and their application in the preparation of antidepressants
  • Asiatic acid derivatives, their preparation methods and their application in the preparation of antidepressants
  • Asiatic acid derivatives, their preparation methods and their application in the preparation of antidepressants

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Preparation and extraction of compound 1:

[0049] Inoculate Gliocladium roseum CGMCC 3.3657 strains of Gliocladium roseum CGMCC 3.3657 with 2% inoculum in 10 bottles of 1000ml (400ml medium per bottle), place in a constant temperature shaker, 180rpm, 27°C for 72 hours, then add 300mg Substrate asiatic acid (dissolved in 20ml of ethanol, 2ml added to each bottle), continued to cultivate for 10 days. After the fermentation is completed, filter the mycelium, extract the filtrate 3 times with equal volumes of ethyl acetate, and extract the mycelia three times with 500ml ethyl acetate ultrasonically, each time for 30min, combine the extract and the extract, and extract the ethyl acetate extract Concentrate to a small volume on a rotary evaporator and dry to obtain conversion reaction extracts (1.8 g).

[0050] Dissolve the conversion reaction extract with a small amount of ethanol, mix the sample with three times the weight of silica gel, separate on 25g of silica gel, and...

Embodiment 2

[0055] Structural identification of compound 1:

[0056] Compound 1 is a white solid, HR-ESI-MS gives 501.3243 ([M-H]-), combined with 1H-NMR and 13C-NMR to deduce that the molecular formula is C30H46O6. In 1H-NMR (600MHz, pyridine-d5), it shows that the compound There are six groups of methyl hydrogen signals δ1.39(3H,o), δ1.17(3H,s), δ1.08(3H,d,6.6), δ1.03(3H,s), δ0.95(3H ,s), δ0.83(3H,s); there is an active hydrogen signal at the downfield: δ5.50(t,3.6), which may be the hydrogen on the double bond. 13C-NMR shows two unsaturated carbon atoms δ125.9 and δ139.8, one carboxyl carbon atom δ179.5. Based on the above information, it can be inferred that the compound is a ursane-type pentacyclic triterpene acid compound.

[0057] According to HSQC and HMBC spectra, the hydrocarbons of compound 1 can be further assigned.

[0058] Compared with asiatic acid, in 1H-NMR spectrum, compound 1 has a hydrogen signal at 3.82ppm (1H, dt, J=4.8, 9.6Hz); in 13C-NMR spectrum, a oxycarbon si...

Embodiment 3

[0063] Structural identification of compound 2:

[0064] Compound 2 is a white solid, HR-ESI-MS gives 503.3401 ([M-H]-), combined with 1H-NMR and 13C-NMR to deduce that the molecular formula is C30H48O6. In 1H-NMR (600MHz, pyridine-d5), the compound is shown With 6 methyl hydrogen atom signals δ1.37(6H,s), δ1.14(3H,s), δ1.07(3H,s), δ1.00(3H,d,6.6), δ0.92( 3H,d,6.6); there is an active hydrogen signal δ5.61(o) at the low field, which may be the hydrogen on the double bond. 13C-NMR shows two unsaturated carbon atoms δ126.4 and δ139.5, and one carboxyl carbon atom δ180.5. Based on the above information, it can be inferred that the compound is a ursane-type pentacyclic triterpene acid compound.

[0065] According to HSQC and HMBC spectra, the hydrocarbons of compound 2 can be further assigned.

[0066] Compared with asiatic acid, in 1H-NMR (600MHz, pyridine-d5), compound 2 has a hydrogen signal at 4.45ppm (1H, dd, J=4.2, 10.8Hz); in 13C-NMR spectrum, at 73.4ppm A oxycarbon sig...

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PUM

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Abstract

The present invention provides an asiatic acid derivative compound conforming to general formula (I) or a pharmaceutically acceptable salt or ester thereof, or any optical isomer, or any tautomer: the present invention also provides the above product The preparation method of the derivative compound of madecasic acid is obtained by modifying the structure of asiatic acid by microorganisms. The present invention also provides a use of the asiatic acid derivative compound as described above or the asiatic acid derivative compound prepared by any of the above preparation methods for the preparation of antidepressant drugs. The asiatic acid derivative compound of the present invention has high antidepressant activity through the forced swimming test of mice and the tail suspension test of mice.

Description

technical field [0001] The invention belongs to the field of natural medicinal chemistry, and relates to a compound, in particular to an asiatic acid derivative and its preparation method and its application in the preparation of antidepressants. Background technique [0002] Asiatic acid, also known as asiatic acid, is an ursane-type pentacyclic triterpenoid extracted from the medicinal Umbelliferae plant Centella asiatica (L.) Urban. Its structural formula is: [0003] [0004] Because Asiatic acid has a wide range of biological activities, it is widely used in the field of natural medicinal chemistry, and has good effects in anti-tumor, improving cognition, anti-diabetes, anti-inflammation, antibacterial, and promoting wound healing. [0005] Depression is a common and easily overlooked mental illness, with significant and persistent low mood as the main clinical feature, and it is the main type of mood disorder. It can be seen clinically that the mood is not commensu...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07J63/00A61K31/56A61P25/24C12P33/00C12P39/00C12R1/645
CPCC07J63/008C12P33/00C12N1/145C12R2001/645
Inventor 储智勇冯旭栾洁邹赢锌陈松张术郭飞飞
Owner NAVY MEDICINE RES INST OF PLA
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