Studies related to anthracyclines. Part 3. Stereoselective synthesis of (+)-daunomycinone

Abstract

The title compound 2b was prepared by a seven-step sequence from (±)-4a,9a–epoxy-4a,9adihydro-5-methoxyanthracene-1,4,9,10-tetraone 3b/3c and (E)-1-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)-3-trimethylsilyloxybuta-1,3-diene 4. Acidic hydrolysis of the crude Diels–Alder cycloadducts of compounds 3b/3c and 4 led, after fractional crystallisation, to the isolation of (5aS,6aR,7S,1OaR,11aR)-5a,11a-epoxy-4-methoxy-5a,6a,7,8,9,10,10a,11a-octahydro-7-(2′,3′,4′,6′-tetra-O-acetyl-β-D-glucopyranosyloxy)naphthacene-5,6,9,11,12-pentaone 6b. The last-cited compound was transformed into (+)-daunomycinone 2b by reduction, ethynylation, oxidation, hydrolysis and hydration steps.