Anthracyclinone antibiotics synthesis

The synthesis of quinones, including anthracyclinone antibiotics and oxidized metabolites of polynuclear aromatic hyditxarbons, has been reviewed. 

During an investigation of approaches to the total synthesis of anthracyclinone antibiotics, it has been found that carbanions derived from phenylacetonitrile add to ethyl cyclohex-2-en-l-carboxylate in a Michael fashion to give, after oxidative decyanation, the y-keto-ester (155) in good yield. 

The compatibility with different functional groups, the remarkable regio-and stereoselectivity, and the development of asymmetric procedures have made benzannulation an attractive methodology for the synthesis of natural products with densely functionalized quinoid or fused phenolic substructures [13-20], Some pertinent examples are the syntheses of vitamins K and E [17], and the production of anthracyclinones or naphtoquinone antibiotics [13, 14a, 15, 21]. 

Hauser has used repetitive annelations of this type tor synthesis of linear aromatic systems. This methodology provides a simple regiospecific route to the tetracyclic system of the antibiotic anthracyclinones. For this purpose 5-ethoxy-2(5Ff)-furanone (2) is used as the Michael acceptor in the first annelation of the anion of 1. After methylation, 3 is obtained in 65% yield. It is then converted into 4, for a second annelation with cyclohexenone or a derivative (5). The reaction results in a tetracyclic hydronaphthacene 6. 

Keywords Anthracyclinones - Anthracycline antibiotics Diastereoselective synthesis Enantioselective catalysis... 

A review of the synthesis of anthracyclinones by elaboration of anthraquinones includes a section on the use of sugars as chiral templates. Glycosylations of the daunomycinones (46)-(48) led to the corresponding daunomycin derivatives (49)-(51). The L-fyxo-, L-arabino- and L-nfeo-isomers of the isorhodomycin compounds (52) have been made and tested for cytotoxicity. Several analogues of the anthracycline antibiotics, eg. (53), having a 1,2,3-triazolyl moiety in the sugar, have been described. ... 

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