Anthracycline antibiotics, syntheses including

The anthracycline antibiotics, which include doxorubicin, daunorubicin, bleomycin, and mitomycin C, inhibit DNA and RNA synthesis. Doxorubicin also interfers with topoisomerase II (a DNA gyrase), the activity of which is markedly increased in proliferating cells. Structurally related to doxorubicin are epirubicin and mitozantrone. The cytotoxic antibiotics are used to treat leukaemias and lymphomas and also for solid tumours in the breast, lung, thyroid and ovary. Cardiotoxicity is the major dose-limiting factor, with arrhythmias and myocardial depression (Bacon and Nuzzo 1993). The chronic phase of cardiotoxicity is a dose-dependent cardiomyopathy that leads to congestive heart failure in 2-10% of patients. Myocardial injury is the result of oxygen free radical formation. Children are particularly sensitive to these cardiotoxic reactions and may require a heart transplant in their later years. Epirubicin is less cardiotoxic than doxorubicin. 

Hamada and Shioiri have employed their modification of the Schdllkopf reaction i.e., DPPA-mediated carboxylic acid activation) in the synthesis of L-daunosamine, the carbohydrate component of several important anthracycline antibiotics, including adriamycin and... 

A review of the synthesis of anthracyclinones by elaboration of anthraquinones includes a section on the use of sugars as chiral templates. Glycosylations of the daunomycinones (46)-(48) led to the corresponding daunomycin derivatives (49)-(51). The L-fyxo-, L-arabino- and L-nfeo-isomers of the isorhodomycin compounds (52) have been made and tested for cytotoxicity. Several analogues of the anthracycline antibiotics, eg. (53), having a 1,2,3-triazolyl moiety in the sugar, have been described. ... 

Screening of microbial products has led to the discovery of a number of growth-inhibiting compounds that have proved to be clinically useful in cancer chemotherapy. Many of these antibiotics bind to DNA through intercalation between specific bases and block the synthesis of RNA, DNA, or both cause DNA strand scission and interfere with cell replication. All of the anticancer antibiotics now being used in clinical practice are products of various strains of the soil microbe Streptomyces. These include the anthracyclines, bleomycin, and mitomycin. 

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