Synthesis and mass spectrometry evaluation of N-cycloalkyl derivatives of carminomycin, daunorubicin and their analogues
E. N. Olsufyeva, B. V. Rozynov
Institute of New Antibiotics, Academy of Medical Sciences of the USSR, Moscow; M. M. Shemyakin Institute of Bioorganic Chemistry, Academy of Sciences of the USSR, Moscow
Abstract: Condensation of carminomycin or daunorubicin with glutaric dialdehyde in the presence of NaBH3CN yielded 3'-deamino-3'-piperidinocarminomycin or 3'-deamino-3'-piperidinodaunorubicin and corresponding (13-R, S)-dihydroderivatives. To prepare similar derivatives of 14-hydroxycarminomycin or doxorubicin, 13-dimethylketals of 14-bromocarminomycin or 13-bromodaunorubicin were used in the reaction of reductive alkylation with glutaric or glycolic dialdehyde to give 3'-deamino-3'-piperidino- or 3'-deamino-3'-morpholino derivatives of 13-dimethylketals of 14-bromocarminomycin or daunorubicin, respectively. After deblocking and subsequent hydrolysis of these compounds 3'-deamino-3'-piperidino- and 3'-deamino-3'-morpholino derivatives of 13-hydro-xycarminomycin or doxorubicin were prepared. Reduction of the antibiotic derivatives under mass spectrometry conditions was demonstrated.
Russian Journal of Bioorganic Chemistry 1990, 16 (6):847-853