Daunomycinone 4-demethoxy, synthesis

Antkracyclinones. A key step in a stereocontrolled synthesis of 4-demethoxy-daunomycinone (4) involves cycloaddition of the epoxide 1 with this diene (2). Later steps follow known transformations. 

Hydroxyketone (J )-10 was used as a chiral substrate in the synthesis of daunorubicinone 7 and its analogue idarubicinone (4-demethoxy-daunomycinone) 9 in the route developed by Wong et al. [24] in which the oxygen function at C-7 was introduced at a late stage of the synthesis. 

Many of the homochiral AB synthons described above have been utilised in syntheses of anthracyclinones which are based on Friedel-Crafts cyclisations. As was noted earlier such reactions often require vigorous conditions, and there is some controversy concerning the enantiomeric purity of the products so obtained. While some groups claim that condensation of the hydroxy ketone 174 with phthalic anhydride in an intimate mixture of sodium chloride and aluminium chloride yields optically pure ( —)-4-demethoxy-7-deoxydauno-mycinone [16, 141] others report a considerable degree of racemisation under virtually identical conditions [135, 142], although the problem may be avoided under the somewhat milder conditions employed in a recent condensation of 174 with phthaloyl dichloride [143]. In contrast, stereochemical integrity of the product is assured under the mild conditions employed in Swenton s carbanion based synthesis of (4-)-daunomycinone 5 [53] and in our Diels-Alder based... 

A synthesis of (+)-4-demethoxy-daunomycinone has utilized the dienyl glucoside (27) to achieve a Diels-Alder reaction on the... 

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