Synthesis method of aryl carbon glycoside compound

A technology of aryl carbon glycosides and synthesis methods, which is applied in the fields of metal catalysis and medicinal chemistry applications, can solve the problems of unfavorable environment-friendly development, poor atom economy, inconvenient use, etc., achieve stable and easy-to-obtain acceptor structures, and promote carbon The effect of hydrogen activation reaction and easy operation

Active Publication Date: 2019-07-26
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This synthetic method has following shortcoming: the one, the promotor of equivalent, the use of initiator (comprising heavy metal mercuric salt, silver salt)
In addition, aryl metal reagents are sensitive to air and water, and are relatively inconvenient to use
The third is the use of equivalent organometallic reagents, cumbersome operation, strict anhydrous and oxygen-free conditions, poor atom economy, and is not conducive to environmentally friendly development

Method used

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  • Synthesis method of aryl carbon glycoside compound
  • Synthesis method of aryl carbon glycoside compound
  • Synthesis method of aryl carbon glycoside compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-9

[0045]

[0046] Add amide material 1-s (26.2 mg, 0.1 mmol, 1.0 equiv), chlorosugar (Donor-1) (112 mg, 0.2 mmol, 2.0 equiv), palladium acetate (2.2 mg, 0.01 mmol, 0.1equiv), acetyl isoleucine (Ac-Ile-OH) (5.2mg, 0.03mmol, 0.3 equiv), potassium acetate (14.7mg, 0.15mmol, 1.5equiv), add 1ml of solvent, cover the reaction vial (There is no need for particularly strict anhydrous and oxygen-free conditions), and stirred at 60°C for 6 hours. After the reaction was complete, the reaction bottle was cooled to room temperature, filtered, concentrated, and separated by column chromatography to obtain the product as a colorless oil. The preparation steps of Examples 1-9 are basically the same, the difference lies in the use of different reaction solvents.

[0047] The investigation of table 1 reaction solvent

[0048]

[0049] a:NMR Yield

[0050] It can be found from Examples 1-9 that when the reaction solvent is PhMe, the yield of Example 6 is the best.

Embodiment 10-17

[0052] The preparation method of embodiment 10-17 is basically the same as the preparation method of embodiment 6, and the only difference is that the divalent palladium metal catalyst selected in embodiment 10-17 is different, specifically as shown in table 2

[0053] The screening of table 2 divalent palladium metal catalyst

[0054]

[0055] a: NMR Yield

[0056] Can find by embodiment 10-17, when divalent palladium metal catalyst is Pd(OAc) 2 , the productive rate of embodiment 6 is the best.

Embodiment 18-23

[0058] The preparation method of Examples 18-23 is basically the same as the preparation method of Example 6, the only difference is that the bases used in Examples 18-23 are different, as shown in Table 3.

[0059] The investigation of table 3 alkali

[0060]

[0061] a: NMR Yield

[0062] Can find by embodiment 18-23, when alkali is potassium acetate, the productive rate of embodiment 6 is the best.

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Abstract

The invention relates to a synthesis method of an aryl carbon glycoside compound. The preparation method includes: stirring amide raw material, sugar donor, divalent palladium metal catalyst, alkali and organic solvent for reaction while heating, cooling to room temperature, directly filtering, spin-drying filtrate, and performing column chromatographic separation to obtain the aryl carbon glycoside compound. Simple and efficient synthesis of the aryl carbon glycoside compound is realized by utilizing a method of Pd catalyzed aromatic hydrocarbon C (sp2)-H activation. The method has quite highuniversality and can be applied to a series of substrates like aryl formic acid, aryl acetic acid, benzylamine and phenol. The method utilizes halogenated sugar as the donor and is simple in synthesis step and suitable for large-scale production and application; guide groups which are used are not limited to 8-aminoquinoline, p-pyridine carboxylic acid and 2-aminopyridine nitrogen oxide and can be used for reaction. A new method and idea is provided for synthesizing a series of complex carbon glycoside drug and natural drug, and synthesis difficulty of carbon glycoside is lowered.

Description

technical field [0001] The invention belongs to the technical field of metal catalysis and medicinal chemistry application, and specifically relates to a synthesis method of aryl carbon glycosides. Background technique [0002] Carbon glycoside refers to the general term for a class of compounds in which the oxygen atoms outside the ring of the carbon glycosidic bond are replaced by carbon atoms. It is a very wide class of sugar-containing skeletons in nature. It is widely found in a variety of natural products and drug molecules. Compared with oxoglycosides and nitrogen glycosides, carboglycosides have better enzyme stability and hydrolysis resistance in vivo, so they have also become an important choice to replace natural oxoglycoside drugs. For example, in recent years, a number of pharmaceutical companies have developed a series of SGLT2 inhibitors for the treatment of type 2 diabetes, including dapagliflozin, canagliflozin, empagliflozin, etc. In addition, the presence...

Claims

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Application Information

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IPC IPC(8): C07D309/10C07D405/12
CPCC07D309/10C07D405/12Y02P20/55
Inventor 陈弓何刚王权权安爽祝婉君
Owner NANKAI UNIV
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