Epirubicin hydrochloride intermediate compound IV

Abstract

The invention provides a novel intermediate and a new route for synthesizing epirubicin hydrochloride by using the intermediate. The route is simple, cheap and efficient, and meanwhile, the problems that the intermediate generated by an existing epirubicin hydrochloride synthesis route is instable in water and easy to decompose and the whole route is low in yield are solved. In order to better achieve energy conservation and emission reduction, a cheap and available reagent is utilized by the route; and meanwhile, removable selective protection means are adopted, so that the generated impurities are few, the purity is high and the yield is high.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to an intermediate compound IV of epirubicin hydrochloride. Background technique [0002] Epirubicin hydrochloride, also known as epirubicin hydrochloride, belongs to anthraquinone antibiotics, chemical name: (8S,10S)-10-[(3′-amino-2′,3′,6′-trideoxy-α -L-arabinosyl)-O-]-6,8,11-trihydroxy-8-glycolyl-1-methoxy-7,8,9,10-tetrahydrotetracene-5 ,12-diketone hydrochloride, its structure is shown below: [0003] [0004] It is an isomer of doxorubicin, and its mechanism of action is to intercalate directly between DNA nucleobase pairs, interfere with the transcription process, and prevent the formation of tumor cell mRNA, thereby inhibiting the synthesis of DNA and RNA. In addition, epirubicin hydrochloride also inhibits topoisomerase II. As a cell cycle non-specific drug, it is effective for a variety of transplanted tumors. The clinical efficacy is equal to or slightly...

AI Technical Summary

Problems solved by technology

The organic solvents used in this method, such as propylene oxide, are extremely harmful to the physical and mental health of producers, and the waste liquid produced is difficult to handle, which puts a huge pressure on the environment; at the same time, the final hydrolysis stage adopts multi-step hydrolysis with different pH conditions, it is difficult to precisely control, and thus puts forward extremely high requirements on the operator's technology, so the production cost of this process is huge, the environment is polluted seriously, and it is not conducive to large-scale industrial production

And this process is relatively harsh to the water content of raw material 4'-epidaunorubicin and the humidity during reaction, in the actual application process, it is found that a slight change in water content will cause excessive 4'-epidaunorubicin residues defects, the final product quality is difficult to guarantee, and the material loss rate is extremely high

[0008] The patent US20070142309 provides a variety of synthetic routes for epirubicin hydrochloride. The synthetic principles are not the same, but basically they all adopt the treatment method of reductive amination with sodium triacetoxyborohydride first, and then bromination of the intermediate produced , sodium formate hydrolysis to obtain the final product epirubicin hydrochloride, the cost of this reagent is higher than that of traditional organic synthesis reagents, and the reagents used are difficult to preserve in the workshop environment, prone to safety production accidents, and are not suitable for industrialized large-scale production

[0009] Therefore, all there is problem in the above-mentioned epirubicin hydrochloride preparation method, or yield is low, impurity is big, or technical requirement is high, environmental pollution is serious, production cost is high, and epirubicin hydrochloride in the prior art The intermediate produced by the preparation method has extremely high requirements for moisture, is easy to decompose, and is not conducive to large-scale industrial production

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