PROCESS FOR OBTAINING ADRIAMYCIN AND ADRIAMYCINONE

摘要

1,217,133. Preparing adriamycin. SOC. FARMACEUTICI ITALIA. 11 April, 1969 [12 April, 1968], No. 18719/69. Heading C2A. The antibiotic adriamycin or its aglycone adriamycinone having the Formula I and non-toxic acid-addition salts of adriamycin are prepared by reacting daunomycin or an N- protected derivative thereof or the aglycone with bromine or iodine to convert the 14-CH 3 group to a 14-CH 2 Br or a 14-CH 2 I group and either reacting with alkali metal acetate to give the 14-acetoxy derivative which is then hydrolysed with alkali to the required 14-CH 2 OH group of adriamycin or, in the ease of the 14-CH 2 Br group, hydrolysing this directly with alkali to the 14-CH 2 OH group, then removing the N-protecting gtoup and optionally converting the adriamycin to an acid-addition salt. N-protecting groups may be the trifluoroacetyl group or the Schiff base with salicaldehyde, which are removed by treatment with ethyl chloroformate and p-toluene-sulphonic acid followed by alkaline hydrolysis in the case of the acyl group or acid hydrolysis when the Schiff base is used. The initial halogenation is carried out in an inert solvent, preferably in the presence of CaO when the halogen is iodine, in an inert atmosphere. Pharmaceutical compositions comprise the antibiotic adriamycin or its aglycone, of Formula I above, or a non-toxic acid-addition salt of adriamycin, when prepared by the aforesaid process, together with a pharmaceutical diluent or carrier.