Anthracyclinone 11-deoxy, synthesis

Michael addition to a complexed styrene. A key step in a synthesis of 11-deoxy-anthracyclinone (3) involves the regioselective reaction of 1 with the carbanion of a protected acetaldehyde cyanohydrin to give 2 by stereospecific earo-addition. 

Preparation of enantiopure intermediates by the use of oxidation reactions was not limited to the synthesis of AB segment (J )-10. The synthesis of the modified daimomycinone, 9-deacetyl-ll-deoxy-9-hydroxymethyldauno-mycinone 44 by Naruta et al. provides an example of enantioselective epox-idation at the stage of a tetracycHc intermediate (Scheme 8) [56]. TetracycUc quinone 42, with the required stereochemistry of the C-4 and C-9 substituents and a protected phenolic hydroxyl group, was prepared in a tandem Michael-Diels-Alder addition of pentadienyltin with acryoylquinone 40 mediated by Lewis acid [57], followed by demethylation, acetylation, and selective hydrolysis. Sharpless enantioselective epoxidation [58] of 42 yielded epoxide 43 in 80% yield and 96% ee. Further transformations of 43 by known procedures, indicated in Scheme 8, furnished the target anthracyclinone 44 in 36% yield from 42. 

Unsymmetrically substituted anthraquinones have been synthesised through addition of the isobenzofuranone 52 to arynes generated in situ from haloarenes, the regioselectivity of the reaction being controlled by substituents in the aryne moiety [61]. This approach is unlikely to allow regiospecific synthesis of anthracyclinones other than 11-deoxy analogues, but the unsubstituted phthalide 51 has been condensed with 68 to give 69, a precursor of 4-demethoxydaunomycinone 6. 

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