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Method for preparing N7-guanine alkylate

A technology of alkylate and guanine, which is applied in the field of preparation of N7-guanine alkylate, can solve the problems of complicated separation and purification, cumbersome preparation process, and limited applicability, and achieve simple separation process, simple operation process, saving washing The effect of removing agent

Inactive Publication Date: 2013-01-09
BEIJING UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The purpose of the present invention is to provide a simple and convenient, easy to get raw materials, high yield N 7 - The preparation method of guanine alkylate mainly solves the technical problems such as cumbersome preparation process, complicated separation and purification, low yield and poor applicability in the existing preparation method

Method used

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  • Method for preparing N7-guanine alkylate
  • Method for preparing N7-guanine alkylate
  • Method for preparing N7-guanine alkylate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1 N 7 - Preparation of ethylguanine

[0032]

[0033] Add 300mg (1.12mmol) of 2'-deoxyguanosine and 6mL of dimethylacetamide into a 25mL round-bottomed flask, and sonicate for 1min. After the 2'-deoxyguanosine is completely dissolved, add iodoethane 0.6mL (7.42 mmol), put into a stirring bar, airtightly stir, react at 25 DEG C for 24h, after the completion of the reaction, distill off the solvent under reduced pressure at 23 DEG C, purify through silica gel column chromatography, use ethyl acetate:petroleum ether (volume ratio)=12 : 1 eluent elution, and then ethyl acetate: anhydrous methanol (volume ratio) = 12: 1 eluent elution to obtain the final product N 7 -Ethylguanine 189mg, the product is a yellow solid, and the yield is 95.3%.

[0034] UVλ: 245, 284nm; 1 H NMR (400MHz, DMSO-d 6 ): δ1.78~1.74 (m, 3H, CH 3 ), 3.87~3.84 (m, 2H, CH 2 ), 6.16(s, 2H, NH 2 ), 7.82 (s, 1H, CH), 11.00 (s, 1H, NH); MS (ESI): m / z 180 (M+H + ).

Embodiment 2

[0035] Example 2 N 7 - Preparation of ethylguanine

[0036]Add 360mg (1.35mmol) of 2'-deoxyguanosine and 9mL of dimethylacetamide into a 25mL round-bottomed flask, and sonicate for 1.5min. After the 2'-deoxyguanosine is completely dissolved, add 1mL of iodoethane (12.37 mmol), put into a stirring bar, airtightly stir, react at 25 DEG C for 20h, after the completion of the reaction, distill off the solvent under reduced pressure at 25 DEG C, purify through silica gel column chromatography, use ethyl acetate:petroleum ether (volume ratio)=15 : 1 eluent elution, and then ethyl acetate: anhydrous methanol (volume ratio) = 15: 1 eluent elution to obtain the final product N 7 -Ethylguanine 234mg, the product is a yellow solid, and the yield is 97.5%. The UV, NMR and mass spectrum data of the product are the same as in Example 1.

Embodiment 3

[0037] Example 3 N 7 Preparation of -(2-hydroxyethyl)guanine

[0038]

[0039] Add 480mg (1.80mmol) of 2'-deoxyguanosine and 9mL of glacial acetic acid into a 25mL round-bottomed flask, sonicate for 2min, and then add 0.6mL (11.86mmol) of ethylene oxide after the 2'-deoxyguanosine is completely dissolved , put into a stirring bar, airtightly stir, and react at 37°C for 1h, after the reaction was completed, the solvent was distilled off under reduced pressure at 35°C, and purified by silica gel column chromatography, using ethyl acetate:petroleum ether (volume ratio)=15:1 The eluent was eluted, and then eluted with ethyl acetate: anhydrous methanol (volume ratio) = 12: 1 eluent to obtain the final product N 7 -Hydroxyethylguanine 339mg, the product is a white solid, and the yield is 96.6%.

[0040] UVλ: 247, 284nm; 1 H NMR (400MHz, DMSO-d 6 ): δ3.73~3.69 (m, 2H, CH 2 ), 4.14~4.12 (m, 2H, CH 2 ), 6.39 (s, 2H, NH 2 ), 8.08 (s, 1H, CH), 10.67 (s, 1H, NH); MS (ESI): m / z 1...

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Abstract

The invention relates to a method for preparing an N7-guanine alkylate. The method comprises the following steps of: reacting 2'-deoxyguanosine serving as a raw material and iodoethane, ethylene oxide, 1-bromo-2-ethyl chloride, 3-allyl bromide or 1,2-dibromoethane serving as an alkylate in a dimethyl sulfoxide, glacial acetic acid or dimethyl acetamide solution at a temperature of 15-50 DEG C for0.5-96 hours; performing reduced pressure distillation after the reaction is finished; separating and purifying a rough product through silica gel column chromatography; and eluting with an eluent comprising acetic ether and petroleum ether in a volume ratio of (10-20):1 and an eluent comprising acetic ether and absolute methanol in the volume ratio of (10-20) :1 respectively to obtain the N7-guanine alkylate. The method has the advantages of mild reaction conditions, simple separation and purification process, high product yield, less environmental pollution and the like and contributes to mass production of the N7-guanine alkylate.

Description

technical field [0001] The invention relates to a preparation method of a class of DNA base modifiers, in particular to N 7 - Process for the preparation of guanine alkylates. Background technique [0002] Base modification is an important form of DNA damage. After exogenous chemical carcinogens or drugs enter the organism, they react with the DNA in the cell to generate base modification products of various structures, resulting in changes in the molecular structure and stability of DNA, which may lead to DNA chain scission, cross-linking, Damage such as base mispairing. The alkylation modification of bases is a common damage product generated by DNA under the action of electrophiles, and some carcinogens induce cancer by causing the alkylation modification of DNA bases. Base alkylation products are generally formed at the nucleophilic site of the base, where the N of guanine 7 The site is the most active of the nucleophilic sites. N 7 -Guanine alkylate is a class of ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D473/18
Inventor 赵丽娇许洁宋秀庆白宝清钟儒刚
Owner BEIJING UNIV OF TECH
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