Gareth John Thomas

Total synthesis of some new 4-demethoxyanthracyclinones

Abstract Optically active 4-demethoxyanthracyclinoiies (39a-g) bearing a variety of substituents at the 9position have been synthesised by an analogous route to that previously employed by us for (+)-4-demethoxydaunomycinone (5). These novel anthracyclinones have been prepared in sufficient quantity for subsequent glycosidation and biological evaluation.

Synthesis of Anthracyclines Related to Daunomycin

The significant antitumour activity of the anthracyclines has stimulated considerable interest in the synthesis of new analogues which have improved therapeutic properties. Synthetic approaches to the tetracyclic aglycone moiety have been based on Friedel-Crafts acylations, base catalysed annulations and Diels-Alder reactions. Whereas the majority of published syntheses lead to racemic aglycones some strategies make use of homochiral synthons obtained by resolution or asymmetric synthesis, or incorporate fragments derived from the chiral pool in the construction of ring A, to give enantiomerically pure aglycones. Daunosamine and related sugars have been synthesised from carbohydrate or non-carbohydrate precursors, and coupling of sugar and aglycone moieties has led to new anthracyclines. Significant synthetic advances reported over the last 5 years are reviewed.