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A kind of preparation method of total synthesis of 4'-desmethyl epipodophyllotoxin

A demethyl epipodophyllin and total synthesis technology, applied in asymmetric synthesis, organic chemistry methods, chemical instruments and methods, etc., can solve the problems of complicated reaction operation, difficult purification of crude products, etc., and achieve low isomer content. , Good chiral induction effect, environmental friendly effect

Active Publication Date: 2022-04-22
SHANGHAI JINHE BIO TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Even so, there are still many problems in the industrial synthesis of podophyllotoxin so far, such as complex reaction operations, the use of many sensitive reagents, and the difficulty in purification of crude products. Therefore, it is of great significance to develop a simple and efficient synthetic route

Method used

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  • A kind of preparation method of total synthesis of 4'-desmethyl epipodophyllotoxin
  • A kind of preparation method of total synthesis of 4'-desmethyl epipodophyllotoxin
  • A kind of preparation method of total synthesis of 4'-desmethyl epipodophyllotoxin

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Synthesis of Compound 2:

[0042] Dissolve 18.1 g of compound 1 syringaldehyde in a three-necked reaction flask filled with 180 mL of tetrahydrofuran, control the temperature at 25-30° C., and stir. Add 19.5g of benzyl chloroformate into the reaction flask in the previous step, stir and drop 115mL of 1N sodium hydroxide solution, the dropping time is controlled at 1.5-2 hours, the temperature is controlled at 25-30°C, after the dropping is completed, stir for 30 minute. After the reaction was completed, the liquids were separated, the organic phase was washed with salt water until neutral, the organic phase was concentrated to dryness, and dried under vacuum at 45° C. by adding phosphorus pentoxide for 8 hours to obtain the product compound 2: 30.9 g, Y=98%.

[0043] Synthesis of compound 4:

[0044] Add 12.1g of compound 3 into a three-necked reaction flask containing 210mL of tetrahydrofuran, under nitrogen protection, freeze the reaction solution to -20~-15°C, slow...

Embodiment 2

[0056] figure 1 HNMR and its analysis of the product prepared for the present invention.

[0057] figure 2 Obtain high performance liquid phase chromatograms for the product prepared by the present invention.

[0058] Adopt conventional high performance liquid phase to detect the product prepared by the present invention, such as figure 2 shown.

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Abstract

The invention discloses a preparation method for the total synthesis of 4'-Demethylepipodophyllotoxin, specifically a complete synthesis of 4'-Demethylepipodophyllotoxin (4'-Demethylepipodophyllotoxin, also known as epipodophyllotoxin). Synthetic preparation method. Including: (1) using syringaldehyde (compound 1) as the initial material, using benzyl methoxy acyl as the protective group, which is conducive to the chemical reaction of the final deprotection group to obtain the target compound; (2) using a chiral catalyst s- The asymmetric hydrogenation reduction reaction involving BINAN Ru(II) produces the chiral target; (3) the chiral catalytic hydrogenation also parallels the hydrogenation and deprotection reaction, which saves the steps and processing of the reaction, and the route selection is suitable for The target compound is more targeted, the production cost is lower, and the environment is more friendly.

Description

technical field [0001] The present invention relates to a process method of anti-tumor drug mother nucleus, relates to a preparation method of epipodophyllotoxin, in particular to a preparation method of total synthesis of 4'-desmethyl epipodophyllotoxin. Background technique [0002] Since the beginning of the 1950s, a lot of work has been done on the structural transformation of podophylloid compounds at home and abroad. Etoposide (Etoposide), Teniposide (Teniposide) and Etopophos (Etopophos) ( Structural formula 1) has been clinically used for the treatment of diseases such as gastric cancer, lung cancer, breast cancer, bladder cancer, testicular cancer and ovarian cancer. The core of these three antineoplastic drugs is 4'-epipodophyllotoxin (4'-Demethylepipodophyllotoxin, also known as: epipodophyllotoxin) (structural formula 2), the main method of obtaining epipodophyllotoxin at present is from podophyllotoxin The natural podophyllotoxin (structural formula 3) is extra...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D493/04C07B53/00
CPCC07D493/04C07B53/00C07B2200/07Y02P20/55
Inventor 张伟中王权勇袁道博石迪升庄凤凤
Owner SHANGHAI JINHE BIO TECH