11-Deoxy anthracyclinone

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. 

Also 2 -halo-3 -hydroxy derivatives of various anthracyclinones show a high activity against P 388 mouse leukemia in certain in-vivo tests. A compound like 98 has been prepared in the 2-deoxy-2-iodo-a-L-ma no-series by Horton et al. [59, 60] starting from di-O-acetyl-L-rhamnal (28). Similarly, Thiem et al. have also successfully prepared the tetracenomycinone-C glycoside 99 [61]. From 4-0-acetyl-3-0-(p-methoxy)-benzyl-L-fucal (102) the glycoside derivatives 103 and 104 in the talo-series were obtained. 

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. 

Some natural products outside the carbohydrate field - particularly those with highly hydroxylated cyclohexane ring components - have been subject to synthetic studies which are dependent on the mercury-based rearrangement reaction the alkaloid (+)-lycoricidine (30) [12] and the cycloheptane-based (+)-calystegine 62(31) which stimulates growth of nitrogen-fixing Rhizobia [29] are examples, and compound 32 which offers novel access to the anthracyclinone components of anthracyclin anti-cancer compounds, has been produced by cycloaddition of a naphthalene-based o-xylylene to a 2,3-unsaturated hex-4-uloside followed by carbocyclization of the product by use of the mercuration procedure [30]. Studies on HMG-CoA reductase inhibitors like compactin have afforded the tetra-carbon-substituted 33 made from a hex-5-enopyranoside with deoxy-branch chains at C-2, C-3 and C-4 [31]. 

Tri-rerf-butyldiphenylsilyl-2-deoxy-D-flrafeino-hexonolactone, on sequential reaction with bromomagnesium(trimethylsilylacetylide), phosphorus oxychloride-pyridine then sodium hydroxide, gave glycal derivative 3. The acetylene moiety was further elaborated into an anthracyclinone system representing the core unit found in vineomycinone B. ... 

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