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Method for synthesizing On-DNA pyrimidine compound

A technology of compound and carbonyl compound, applied in the field of coding compound library, can solve the problem of no report

Active Publication Date: 2021-06-08
HITGEN INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004]Pyrimidine compounds are an important class of drug compound skeleton structure, but there is no report on the synthesis of On-DNA pyrimidine compounds through On-DNAα,β-unsaturated carbonyl compounds Methods

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  • Method for synthesizing On-DNA pyrimidine compound
  • Method for synthesizing On-DNA pyrimidine compound
  • Method for synthesizing On-DNA pyrimidine compound

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Embodiment 1

[0059] The synthesis of embodiment 1, On-DNA pyrimidine compound

[0060] Step 1, On-DNA α, the synthesis of β-unsaturated carbonyl compound

[0061]

[0062] Dissolve the On-DNA arylethanone compound (1) in 250 mM, pH=9.4 boric acid buffer solution to prepare a 1 mM concentration solution (20 μL, 20 nmol), and add benzaldehyde (4000 nmol, 200 equivalents, 200mM DMSO), sodium hydroxide (10000nmol, 500 equivalents, 500mM double-distilled water), mix well, and react at 30°C for 2 hours.

[0063] After the reaction is completed, carry out ethanol precipitation: add a total volume of 10% 5M sodium chloride solution to the reacted solution, and then continue to add 3 times the total volume of absolute ethanol, shake evenly, and place the reaction in dry ice to freeze After 0.5 hours, centrifuge at 12000rpm for half an hour, pour off the supernatant, and dissolve the remaining precipitate with deionized water to obtain a solution of On-DNAα,β-unsaturated carbonyl compound (2). ...

Embodiment 2

[0067] The synthesis of embodiment 2, On-DNA pyrimidine compound

[0068] Step 1, On-DNA α, the synthesis of β-unsaturated carbonyl compound

[0069]

[0070] Dissolve the On-DNA arylethanone compound (1) in 250 mM, pH=9.4 boric acid buffer solution to prepare a 1 mM concentration solution (20 μL, 20 nmol), and add benzaldehyde (4000 nmol, 200 equivalents, 200mM DMSO), sodium hydroxide (10000nmol, 500 equivalents, 500mM double-distilled water), mix well, and react at 30°C for 2 hours.

[0071] After the reaction is completed, carry out ethanol precipitation: add a total volume of 10% 5M sodium chloride solution to the reacted solution, and then continue to add 3 times the total volume of absolute ethanol, shake evenly, and place the reaction in dry ice to freeze After 0.5 hours, centrifuge at 12000rpm for half an hour, pour off the supernatant, and dissolve the remaining precipitate with deionized water to obtain a solution of On-DNAα,β-unsaturated carbonyl compound (2). ...

Embodiment 3

[0075] The synthesis of embodiment 3, On-DNA pyrimidine compound

[0076]

[0077] 21 kinds of On-DNA α, β-unsaturated carbonyl compounds were dissolved in 250mM, pH = 9.4 boric acid buffer solution to prepare a 1mM concentration solution (20μL, 20nmol), and phenylamidine (8000nmol, 400 equivalents) was added to the solution , 400mM DMSO), NaOH (10000nmol, 500 equivalents, 1000mM double distilled water) were mixed uniformly, and after reacting at 80°C for 2 hours, simple iodine (2000nmol, 100 equivalents, 200mM THF) was added to the system and mixed uniformly, and reacted at 30°C for 1 hour.

[0078] After the reaction is completed, carry out ethanol precipitation: add a total volume of 10% 5M sodium chloride solution to the reacted solution, and then continue to add 3 times the total volume of absolute ethanol, shake evenly, and place the reaction in dry ice to freeze After 0.5 hours, centrifuge at 12,000rpm for half an hour, pour off the supernatant, and dissolve the rema...

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Abstract

The invention relates to a method for synthesizing an On-DNA pyrimidine compound, which is characterized in that an On-DNA alpha, beta-unsaturated carbonyl compound reacts with an amidino compound to obtain the On-DNA pyrimidine compound. The reaction method can be carried out in a mixed water phase of an organic solvent / water phase, is simple to operate, introduces no metal reagents, is environmentally friendly, and is suitable for synthesizing a DNA coding compound library by using a porous plate.

Description

technical field [0001] The invention belongs to the technical field of encoded compound libraries, and in particular relates to a method for synthesizing On-DNA pyrimidine compounds in the construction of DNA encoded compound libraries. Background technique [0002] In drug development, especially new drug development, high-throughput screening for biological targets is one of the main means to quickly obtain lead compounds. However, the traditional high-throughput screening based on a single molecule requires a long time, huge investment in equipment, limited number of library compounds (millions), and the construction of a compound library requires decades of accumulation, which limits the efficiency and efficiency of lead compound discovery. possibility. The DNA-encoded compound library technology (WO2005058479, WO2018166532, CN103882532) that has emerged in recent years combines combinatorial chemistry and molecular biology techniques to add a DNA tag to each compound a...

Claims

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Application Information

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IPC IPC(8): C07H21/04C40B50/10C40B40/06
CPCC07H21/04C40B50/10C40B40/06Y02P20/55
Inventor 李进杜甜伍荣峰高森刘观赛万金桥
Owner HITGEN INC