Chemical semi-synthetic process of 10-hydroxycamptothecin

Abstract

The invention discloses a semisynthesis method for 10-hydroxycamptothecin, which takes camptothecin as a raw material to prepare the 10-hydroxycamptothecin through the combination of catalytic hydrogenation and oxidation. The method is characterized by realizing a process of the combination of hydrogenation and oxidation, saving operation steps, in particular improving a catalyst by using a Pd / C catalyst containing 5 to 10 percent of palladium and recycling the catalyst, improving the manageability of the reaction by changing high-temperature reaction to normal-temperature reaction, and improving the selectivity of oxidation by applying oxidizers such as 2-iodoxybenzoic acid during the oxidation reaction. Compared with the prior art, the method has the advantages of hydrogenation reaction which is simple and convenient in operation and is low in cost, oxidation reaction which is high in selectivity, total yield of the two reactions of the whole production process which is increased to more than 85 percent, and suitability for industrial production.

Description

technical field [0001] The present invention relates to 10-hydroxycamptothecin, more specifically to a chemical semi-synthesis method for 10-hydroxycamptothecin. Background technique [0002] The domestic clinical demand and export volume of camptothecin drugs are increasing year by year because of their less toxic and side effects and high antitumor activity. In order to meet the needs of the market, more and more attention has been paid to the synthesis of such drugs, especially the preparation of hydroxycamptothecin, because it is not only an antitumor drug with better clinical effect, but also the preparation of irinotecan And topotecan and other important intermediates of camptothecin derivatives. Therefore, it is of great practical significance to study the preparation process of hydroxycamptothecin. [0003] The chemical structure of 10-hydroxycamptothecin (10-Hydroxycamptothecin, HCPT) is similar to that of camptothecin, except that the hydrogen on the 10th positio...

AI Technical Summary

Problems solved by technology

This scheme adopts Aspergillus flavus T-419 bacterial strain, has improved biotransformation rate, has certain economic effect and development potentiality, but this technology is not mature enough, there is following shortcoming: (1) the cultivation of bacterial strain needs to spend time long, needs There are many equipments and harsh culture conditions; (2) The concentration of the product in the fermentation broth is low, the extraction process is cumbersome, the amount of extraction solvent is large, and the environment is seriously polluted

Although E.J. Coery had realized the chiral total synthesis of camptothecin in 1975, the synthetic route was as long as 21 steps, and the total synthetic yield was only 0.3%.

After the 1980s, scientific researchers continued to improve the total synthesis method of camptothecin, which increased the total yield. However, due to too many steps, the yield was low, and the cost was too high, so that its industrialization could not be realized.

However, these improved methods still have a series of problems such as expensive precious metal platinum, high cost, high-pressure hydrogenation reaction must be carried out in an autoclave, complex operation, and potential safety hazards.

Images