Anthracycline antibiotics asymmetric synthesis

In the total synthesis of an anthracycline antibiotic, the key step was an asymmetric halolactonization reaction. The corresponding bromolactones were formed with high stereoselectivity (d.s. > 90%). (S)-Proline was used as chiral auxiliary. 

This reaction was used for an asymmetric synthesis of aklavinone (8), an aglycone of the anthracycline antibiotics. The key step was the reaction of the acetal 6 with 2,... 

A new asymmetric synthesis of anthracycline antibiotics such as ( + )-4-demeth-oxydaunomycinone (5) is based on dihydroxylation of 1 with Os04 in the presence of the diamine (-)-2, which provides the diol 3 in 82% ee.5 The product is converted into (+)-5 by four known reactions. 

Several of the anthracycline antibiotics are highly effective against a wide variety of tumours, but possess a toxicity that severely limits dosage. In consequence considerable efforts have been directed towards modification of structure, and in one case lowering of toxicity has been achieved by replacing the carbohydrate moiety L-daunosamine (115) by its C-4 epimer L-acosamine (116). A chiral synthesis of both these compounds has now been reported. The key step is an intramolecular nitrone-olefin cycloaddition [(112) -> (113) and (114) in a ratio of 82 18] in which the chiral side-chain exerts considerable asymmetric induction. The major isomer (113) could be converted to either (115) or (116) by conventional means. 

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