The Synthetic Routes of Doxorubicin hydrochloride

Doxorubicin hydrochloride, also known as adriamycin, is an anthracycline-type chemotherapy drug that is commonly used to treat various types of cancer, including breast cancer, ovarian cancer, and leukemia.
The synthesis of doxorubicin hydrochloride has been widely studied and has been the subject of numerous articles and reviews in the literature.

One of the most common synthetic routes for doxorubicin hydrochloride involves starting with the synthesis of the anthracycline base, which is then converted to the hydrochloride salt.
The anthracycline base can be synthesized from a variety of starting materials, including 2,4-diamino-5-iodothyrophenol (DAITP) and 2,4-diamino-6-methylaminopyridine (DMAP).

One common synthesis route for the anthracycline base involves treating DAITP with sodium hydroxide in aqueous solution, followed by treatment with a Collins reagent, such as 1,3-dicyclohexylcarbodiimide (DCC) and hydrochloric acid (HCl).
This results in the formation of the N-hydroxyanthracycline intermediate, which can then be transformed into the anthracycline base by treatment with an alcohol, such as methanol or ethanol.

Once the anthracycline base has been synthesized, it can be converted into the hydrochloride salt by treatment with hydrochloric acid.
The resulting doxorubicin hydrochloride can be isolated and purified using standard techniques, such as precipitation, filtration, and chromatography.

Another synthetic route for doxorubicin hydrochloride involves starting with the synthesis of the anthraquinone base, which is then converted to the anthracycline base and finally to the hydrochloride salt.
This route is often more efficient than the traditional route and has been widely used in industrial-scale synthesis of doxorubicin hydrochloride.

The anthraquinone base can be synthesized by treating phenylglyoxalate with sodium hydroxide in aqueous solution, followed by treatment with potassium quinone in the presence of sodium hydroxide.
The resulting anthraquinone can then be treated with N,N-dimethylformamide and sodium hydroxide to convert it into the anthraquinone-2-carboxylic acid.

The anthraquinone-2-carboxylic acid can then be converted into the anthracycline base by treatment with an alcohol, such as methanol or ethanol, in the presence of a Lewis acid catalyst, such as aluminum chloride or ferric chloride.
Finally, the resulting anthracycline base can be converted into the hydrochloride salt using hydrochloric acid.

Overall, the synthesis of doxorubicin hydrochloride can be achieved through various synthetic routes, each with its own advantages and disadvantages.
The choice of synthesis route will depend on the availability of starting materials, the scale of production, and the desired purity and yield of the final product.
Regardless of the synthetic route chosen, the final product must be thoroughly purified and tested to ensure its safety and effectiveness for use in cancer treatment.