Epirubicin hydrochloride intermediate compound

Abstract

The invention provides a novel intermediate and a novel route for synthesizing epirubicin hydrochloride by utilizing the intermediate. The route is simple, cheap and efficient, achieves better energy conservation and emission reduction, and avoids the problems that an intermediate generated by the existing epirubicin hydrochloride synthesis route is water-instable and easy to decompose and a yield of the whole route is low. The route uses a low-cost and easy-to-obtain reagent and adopts a removable selective protection means; generated impurities are few; the purity is high; a yield is high.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to an intermediate compound 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 hi...

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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