PROCESS OF PREPARATION OF WATER-SOUBLE ANALOGS OF CAMPTOTHECIN AND INTERMEDIATE FOR THEIR USE, AS WELL THE COMPOUNDS PRODUCED BY THIS PROCESS

摘要

The invention comprises a process of purification of camptothecin or 11-alkoxycamptothecin according to which a mixture of one of these natural products and impurities is brought in contact with a solvent which is capable of separating from it different alkaloides as well as impurities which are hindering the hydrogenation of these compounds to respective tetrahydro analogs. Camptothecin or 11-alkoxycamptothecin is then separated from the mixture. It comprises the process of hydrogenation of on this way purified camptothecin or 11-alkoxycamptothecin to respective tetrahydro analogs where the starting material is brought in contact with hydrogen and an hydrogenation catalyst in the presence of a moderator. 11-alkoxy-1,2,6,7-tetrahydro camptothecins produced according to this process are new compounds. Further on, the invention comprises a process of oxidation of tetrahydro analogs where camptothecin or 11-alkoxytetrahydrocamptothecin is brought in contact with an oxidant in a liquid reaction medium. 10-hydroxy-11-alkoxycamptothecins obtained by this procedure are new compounds. Finally, the invention comprises the process of production of water-soluble derivatives of camptothecin substituted in the position (9) by a group having a formula -CH2R1 where R1 represents -OR2, -SR3 or -NR4R5. First, a 10-hydroxy analog is transformed to a compound with the formula CH2(NR4R5)2, then the amino group, if needed, is transformed to an -OR2 or -SR3 group. Water-soluble analogs of camptothecin represent new compounds and are useful for inhibition of cell growth of tumours sensitive to such analogs.