Total synthesis of premithramycinone H and related anthrapyran antibiotics

Two approaches are described for the preparation of 2-(1',3'-dioxoalkyl) -substituted 1-hydroxyanthraquinones 10a-d and 20a-c, which were cyclized in a biomimetic-type reaction to the anthra[1,2-b]pyran skeletons 11a-d and 21a-c of the heydamycin- or pluramycin-type antibiotics. Cleavage of the methyl ethers afforded the natural product premithramycinone H (2). The simple derivative 11b showed inhibition of the A431 cell line in mumolar concentrations. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).