Preparing method of 1,2,3-tris-O-acetyl-5-deoxy-beta-D-ribose

Abstract

The invention discloses a preparing method of 1,2,3-tris-O-acetyl-5-deoxy-beta-D-ribose, and belongs to the field of synthesis of nucleosides in organic chemistry. The preparing method includes the steps of making inosine 1 react with halogenated sulfoxide to obtain a compound 2, reducing the compound 2 under the conditions of hypophosphorous acid and AIBN, adding methyl alcohol for deprotection to obtain a compound 3, and making the compound 3 react in acetic anhydride under the catalysis of inorganic boric acid to obtain 1,2,3-tris-O-acetyl-5-deoxy-beta-D-ribose. The synthesis method is lowin raw material price, short in step and easy to industrially produce and has industrial application prospects.

Description

technical field [0001] The invention belongs to the field of nucleoside synthesis in organic chemistry, and specifically relates to a preparation method of 1,2,3-tri-O-acetyl-5-deoxy-β-D-ribose. Background technique [0002] 1,2,3-Tri-O-acetyl-5-deoxy-β-D-ribose, CAS: 62211-93-2, is mainly used in the synthesis of capecitabine. Capecitabine is a new anti-tumor drug developed by Roche, which was approved by the FDA in 1998 and listed in the United States under the trade name XELODA (Xeloda). It is suitable for the first-line treatment of inoperable advanced or metastatic gastric cancer, adjuvant chemotherapy for colon cancer, chemotherapy for colorectal cancer, single-drug chemotherapy or combined chemotherapy for breast cancer. [0003] There are many reports on the process route of capecitabine in public information, and the representative patent WO2009071726A1 once disclosed the synthesis method of capecitabine, which uses 5-fluorocytosine as the starting material, and th...

AI Technical Summary

Problems solved by technology

The starting raw material inosine cost of this route is lower than D-ribose, but its shortcoming is: with iodine as iodide reagent, molecular utilization rate is low, and produce more black in the process of iodide and deiodination Iodine-containing wastewater increases the pressure on the treatment of the three wastes; a large amount of expensive triphenylphosphine is used in the iodination reaction, and the triphenylphosphine produced by the reaction is difficult to remove, which brings difficulties to the post-reaction treatment and purification; The yield is low, and the total yield in actual operation does not exceed 60%.

The safety of the equivalent sodium borohydride used in this method is poor, and a large amount of hydrogen is generated during quenching, which has obvious safety hazards.

At the same time, when it is enlarged to the kilogram scale, even if an equivalent amount of p-toluenesulfonylation is used, except for the 5-position, a significant amount of 2-position p-toluenesulfonylation by-products (about 12-14%) are produced, which is not easy to purify. The body can be directly introduced into the final product, causing the product to exceed the standard

[0008] For scale-up, there are different degrees of deficiencies in various routes, and the subtle structural changes of nucleosides will have obvious differences in the properties of specific reactions.

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