Biinomenine derivative connected with C-C bond, preparation method and application thereof

A bis-sinomenine, biological preparation technology, applied in the direction of medical preparations containing active ingredients, drug combinations, pharmaceutical formulas, etc.

Inactive Publication Date: 2008-03-26
NANJING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Throughout the above literature, there are few studies on the structural modification of the A ring in sinomenine, and there have been no reports on the structural modification of sinomenine by using microbial transformation methods.

Method used

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  • Biinomenine derivative connected with C-C bond, preparation method and application thereof
  • Biinomenine derivative connected with C-C bond, preparation method and application thereof
  • Biinomenine derivative connected with C-C bond, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] The stereoselective biosynthesis of carbon-carbon-linked double sinomenine, the synthetic route is:

[0048]

[0049] The strain Antrodiella semisupina was cultured on a slant medium at 25°C for 7 days, then inoculated into sterilized 2L transformation medium, cultured on a shaker for 4 days (25°C, 150r / min), and added through a 0.1μm microporous filter membrane Sinomenine hydrochloride was added at a concentration of 250μg / ml, and the culture was continued for 4 days under the same conditions. The transformed liquid was filtered, and the hyphae was rinsed with a small amount of distilled water with pH 6.0. After combining, a total of 2100ml of filtrate was obtained. The pH value was adjusted to 8-9 with ammonia water, and extracted with dichloromethane several times. The dichloromethane extracts were combined and anhydrous sulfuric acid. Dry with sodium, filter, and spin to evaporate the solvent to obtain 450 mg of solid powder. The transformed product was separated by a...

Embodiment 2

[0053] The stereoselective biosynthesis of carbon-carbon-linked bis-deazamethylsinomenine, the synthetic route is:

[0054]

[0055] The method is the same as in Example 1, but the substrate is N-norsinomenine, and 100 mg of deazamethylbissinomenine is obtained, and the yield is 20%.

[0056] Norbissinomenine A(3): positive ion ESI-MS m / z 609[M+H] + .

[0057] Hydrogen spectrum (solvent Chloroform-d): 6.30 (1H, s, 2-H), 3.75 (3H, s, 3-OCH3), 2.51 (1H, d, J = 15.6 Hz, 5-H), 4.37 ( 1H, d, J = 15.6 Hz, 5-H), 3.49 (3H, s, 7-OCH3), 5.38 (1H, d, J = 2.4 Hz, 8-H), 3.36 (brt, J = 4.0 Hz, 9-H), 2.75 (1H, dd, J=18.4, 5.6Hz, 10-H), 2.19 (1H, brd, J=18.4Hz, 10-H), 2.90 (1H, brs, 14-H), 2.02 (1H, brd, J = 12.2 Hz, 15-H), 1.72 (1H, td, J = 13.0, 3.9 Hz, 15-H), 2.85 (1H, dd, J = 13.0, 3.9 Hz, 16-H) ), 2.60 (1H, td, J=13.0, 3.9 Hz, 16-H). The other half from 1'to 17' is the same as 1 to 17.

[0058] Carbon spectrum (solvent Chloroform-d): 131.0(C-1), 110.4(C-2), 145.1(C-3), 56.0(C-3-OCH3), 143....

Embodiment 3

[0061] The chemical synthesis of carbon-carbon-linked double sinomenine, the synthetic route is:

[0062]

[0063] Method A: Add 200 mg (0.61 mmol) of sinomenine to the reaction flask, dissolve it in 20 ml of methanol, add 1 g (11.5 mmol) of manganese dioxide, and stir at room temperature to react for 48 hours. After centrifugal separation, the supernatant was taken and concentrated under reduced pressure to obtain a brown oil. White compounds 1 (about 60%) and 6 (about 40%) were separated by silica gel column chromatography (chloroform-methanol 15:1V / V).

[0064] Method B: Add 200 mg (0.61 mmol) of sinomenine hydrochloride to the reaction flask, dissolve it in 20 ml of water, add 10 ml of 50 mM potassium permanganate solution, stir at room temperature, and check the progress of the reaction by TLC. When the reaction is terminated, ammonia water is added to adjust the pH to 8.0-9.0, and the mixture is extracted with 100 ml of dichloromethane. The organic phase is dried with anhy...

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Abstract

The present invention discloses one kind of sinomenine derivative connected in C-C mode and its preparation process and antiphlogistic and antotumor effects. The sinomenine derivative is prepared with sinomenine as the parent material and through C-C connection in the place 1 biologically and / or chemically. The sinomenine derivative has, the pharmcodynamical experiment shows, high antiphlogistic and antotumor bioactivity, and possesses latent medicinal application foreground.

Description

1. Technical Field [0001] The invention relates to a compound and a preparation method thereof, in particular to a double sinomenine derivative connected in a carbon-to-carbon manner and a method for preparing the sinomenine derivative by microbial transformation and / or chemical synthesis. The compound also provided by the present invention has potential drug application prospects in the field of anti-inflammatory and anti-tumor. 2. Background technology [0002] Sinomenine is the most effective alkaloid drug extracted from the rhizomes of the fangchiaceae plant Cyclobalanopsis sinensis and Caulis sinensis, which is clinically used to treat rheumatism, rheumatoid arthritis, joint swelling and other diseases. Anti-inflammatory, analgesic, antihypertensive and anti-cerebral ischemia and other pharmacological effects. [0003] Through the modification of the structure of sinomenine, it is the current research hotspot to find novel and more efficient sinomenine derivatives, and the s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D221/28C12P17/16A61K31/485A61P29/00A61P35/00
Inventor 李建新邓张双
Owner NANJING UNIV
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