Daunorubicin and adriamycin are anthracycline glycosides which are clinically useful chemotherapeutic agents against cancer. The synthesis of analogues in which the carbohydrate component is functionally and/or configurationally altered is of great biochemical and practical interest, particularly with the finding that the semisynthetic analogues possessing an inverted configuration at C-4' display high activity against experimental tumors in mice, while the β anomers have a much lower biological activity. It is apparent, therefore, that the stereospecific synthesis of glycosides in this class of compounds is of paramount importance. To date, all glycosidations in this series have been carried out by the classical Koenigs-Knorr procedure and have led to anomeric mixtures that necessitated separation. We report herein on the stereocontrolled synthesis of 7-O-(3-amino-2,3-dideoxy-α-L-arabino-hexopyranosyl)daunomycinone (4), via an acid-catalyzed glycosidation of a glycal intermediate, and the chemical conversion of 4 into the corresponding adriamycin analogue 5. The key intermediate for the stereocontrolled glycosidation of daunomycinone, 1,2,3-trideoxy-4,6-di-O-p-nitrobenzoyl-3-trifluoroacetamido-L-arabino-hex-1-enopyranose (10), was prepared from methyl 4,6-O-benzylidene-2-deoxy-α-L-ribo-hexopyranoside following procedures available in the literature for the D series. Biological activity of compounds 4 and 5 is lower, on a weight basis, than that of daunorubicin and adriamycin both on cultured cells and on ascites sarcoma 180 in mice. This lower degree of efficacy could not be known a priori from the available knowledge about the biochemical mode of action of the antitumor anthracyclines. The new analogues are, on the other hand, definitely less toxic than the corresponding 6'-deoxy derivatives with L-arabino configuration which cause toxic deaths in the treated animals at doses higher than 5 mg/kg (treatment ip on day 1).