Anthracyclines, process for their preparation, intermediates and pharmaceutical formulation

摘要

A class of antitumour anthracycline glycosides of the general formula (I) and (II) is described: in which R<1> = H, OCH3 and R<2> = H, OH. The starting material which is used represents 4'-epidaunorubicin or its 4-demethoxy analogue, which are reacted after protection of the amino group in the sugar component as benzophenone Schiff's base with trifluoromethanesulphonic anhydride to obtain the corresponding 4'-epi-4'-O-trifluoromethanesulphonates from which, after treatment with n-tetrabutylammonium fluoride and subsequent mild acid hydrolysis of the N-protective group, the daunorubicin derivatives of the formula (I) and (II) are obtained as a mixture of the free bases. Chromatography on a buffered silica gel column allows separation of compounds (I) and (II) which are finally isolated as hydrochlorides and, where appropriate, converted into their doxorubicin analogues via the corresponding 14-bromo derivatives and subsequent hydrolysis with aqueous sodium formate.