Aclarubicin, discovered by Umezawa in 1975, is a new cytostatic anthracycline antibiotic. It is one of the anthracyclines with the lowest cardiotoxicity, it is not mutagenic and it stimulates differentiation of tumour cells. The therapeutic index of aclarubicin (efficacy related to toxicity) is higher than that of doxorubicin and daunorubicin, using a proper dose schedule. Single dose therapy of aclarubicin shows only marginal efficacy, whereas multiple divided dose therapy exhibits efficacy comparable to that of doxorubicin and daunorubicin. Thus for clinical trials two dose schedules were designed: 25 mg/m2/day, days 1-7 for acute leukaemia; and 30 mg/m2/day, days 1-4 for solid tumours. Aclarubicin was shown to be highly active in acute leukaemia with 58% complete remissions in first relapse of AML. Good results were also seen in acute leukaemia in combination with cytosine arabinoside and thioguanine. In clinical trials with breast cancer and thyroid cancer the efficacy was in the same range as would be expected for doxorubicin, but side-effects were markedly reduced. Anorexia, mild nausea and infrequent vomiting were observed. Myelosuppression was common but dose reduction was not necessary. There was no alopecia and no congestive heart failure.
Abstract The cycloaddition reaction of the diene (II) with the naphthoquinone (I) gives the adduct (III) (space group P2 1 /n; Z=4) which is transformed to the title compound (VII) as shown.
Abstract A key step in the first synthesis of racemic altersolanol A ( 1a ) is the regioselective Diels‐Alder reaction of 5‐acetoxy‐7‐methoxy‐1,4‐naphthoquinone ( 12 ) with 2‐methyl‐1‐(trimethylsiloxy)‐1,3‐butadiene ( 13 ) to afford the adduct 14 . The structure of 14 has been confirmed by X‐ray measurements. The hydroxy groups of ring A are introduced by epoxidation of 14 to 20 , rearrangement to the allylic alcohol 26 , epoxidation to 31 , and opening of the oxirane to rac ‐altersolanol A ( 1a ). Similar products were obtained starting from juglone ( 15 ). Many of the intermediate epoxides and also compounds 42 – 44 show remarkable cytotoxicity in cell cultures but all compounds were too toxic to be useful as anticancer agents.
