Total Synthesis of 11-Deoxyanthracyclines: 4-Demethoxy-11-deoxydaunomycin, 11-Deoxydaunomycin, and Their Analogues

Abstract

Practical total synthesis of 11-deoxyanthracyclinones (8 and 9) was accomplished on the basis of two effective syntheses of the key intermediates (14 and 15) and the subsequent highly stereoselective introduction of a C-7 cis-hydroxyl group. Glycosidation of 8 with a suitably protected L-daunosamine (37) followed by deprotection provided 4-demethoxy-11-deoxydaunomycin (5). The C-13 acetal derivative (34) of 9 was successfully employed for the glycosidation to achieve the first total synthesis of 11-deoxydaunomycin (6). Two novel synthetic 11-deoxyanthracyclines (10 and 11) possessing a neutral sugar instead of L-daunosamine were also synthesized.