Doxorubicin has the widest spectrum of antitumor activity of all antineoplastic agents and is the most utilized anticancer drug worldwide. Unfortunately there are several tumor types that do not respond to doxorubicin and, furthermore, its effectiveness is restricted due to acute bone marrow toxicity, cardiotoxicity and drug resistance development. More than 2000 analogues have been synthesized and tested and among them idarubicin has better in vivo activity at lower dose. In 1979 our group disclosed a combinatorial approach to the synthesis of linearly condensed six-membered ring systems, a method based on the three component condensations through two successive Diels-Alder additions. The method has been developed to generate various anthracyclinones of biological interest, including enantiomerically pure idarubicinone and a series of DNA intercalators that are mimics of anthracyclines of the type 6-(aminoalkyloxy)methyl-6,7-dideoxyidarubicinones. Since the syntheses of anthracyclines has been reviewed extensively we shall restrict ourselves to the presentation, of our combinatorial approach and discuss the concepts and principles involved. We shall describe the synthetic methods developed for the preparation of the starting tetraenes, that are 2,3,5,6-tetramethylidene-7-oxabicyclo[2.2.1]heptanes, and for the preparation of enantiomerically pure L-daunosamine and analogues, sugars found in the bioactive anthracyclines. This work has required the development of a series of chiral auxiliaries that are monocarboxylic derivatives, the RADO(R)-Cl and SADO(R)-Cl which were obtained in a few steps from the readily available (R,R)- and (S,S)-tartaric acid, respectively. These chiral auxiliaries have allowed one to generate a number of new enantiomerically pure dienophiles, the Diels-Alder additions of which can lead to diastereomerically pure adducts intermediates in our syntheses.