Synthesis process of fluoronucleoside

Abstract

The invention relates to a synthesis process of fluorinated nucleosides, comprising the following steps: step 1, refluxing cytosine and hexamethyldisilazane under the catalysis of ammonium sulfate, then adding isopropanol, and raising the temperature, Obtain a cytosine silyl ether protecting group solution; step 2, dissolve the glycosyl compound in isoamyl alcohol and stir, then add a catalyst and heat to obtain a glycosyl compound solution; step 3, drop the glycosyl compound into the cytosine silyl ether protecting group solution Add the glycosyl compound solution, after the dropwise addition, continue to keep warm for an hour, then filter with suction, add hydrochloric acid dropwise to the filtrate to precipitate a solid, and obtain an intermediate after drying; step 4, the intermediate Carry out the deprotection of the hydroxyl group to obtain the fluorinated nucleoside. The invention not only ensures the formation of the target intermediate configuration, but also greatly reduces the temperature, which not only reduces the requirements for equipment, improves the safety of operation, but also reduces energy consumption, which is beneficial to reduce costs, and is suitable for large-scale production applications .

Description

technical field [0001] The invention relates to a synthesis process of nucleoside derivatives, in particular to a synthesis process of fluorinated nucleosides. Background technique [0002] Nucleoside is the main component of nucleic acid. Some nucleosides and their derivatives have significant physiological functions. For example, inosine (inosine) can treat acute and chronic hepatitis and rheumatic heart disease, and has the effect of increasing white blood cells. . 5-Fluorouracil deoxynucleoside can anti-tumor, and its toxicity is lower than that of 5-fluorouracil. It has certain curative effect on liver cancer, gastric cancer, rectal cancer, ovarian cancer and bladder cancer. Cytosine arabinoside has a significant effect on remission of leukemia. Therefore, it is of great significance to study the synthesis process of nucleoside derivatives. [0003] Fluorinated nucleosides are a class of novel nucleoside derivatives, which have good chemical and enzymatic stability, ...

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Problems solved by technology

[0006] CN105693795A (published on June 22, 2016) discloses a preparation method of difluoronucleoside anticancer drugs, which uses cytosine as a raw material and hexamethyldisilazane to form a silane protecting group Then dock with 2-deoxy-2,2-difluoro-D-erythro-pentafuranose-3,5-diphenylmethyl ester-1-methanesulfonate to obtain the final product after hydrochloric acid post-treatment, but this method Add the cytosine protecting group solution to the glycosyl compound solution dropwise at a high temperature of 128-132°C. This high temperature not only increases the requirements for equipment, but also reduces the safety of operation, and also increases energy consumption, which is not conducive to reducing costs.

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