Experiments Directed Towards the Synthesis of Anthracyclinones. XXV. Synthesis of a Vineomycinone B₂ Methyl Ester Intermediate From Anthrarufin

Abstract

6-(1'-Formyl)-1,5-dimethoxy-2-(2″-oxopropyl) anthraquinone (1), a key intermediate in Danishefsky's synthesis of vineomycinone B₂ methyl ester (5), has been prepared by a new route from anthrarufin (6) via the intermediate 1-methoxy-2-(2′-methylprop-2′-enyl)-5-(2′-methylprop-2′-enyloxy) anthraquinone (20). An alternative synthesis of the diketone (40) has been achieved via Claisen rearrangement of (20) and a subsequent ozonolysis of the resulting bis ( methylpropenyl ) anthraquinone (26). Other routes to (1) from anthrarufin have been developed. In one, compound (1) was formed in yields of 10-16% as an anomalous product from the ozonolysis of (27). Ozonolyses of mixtures of (27), (37) and (44), obtained by isomerization of (27), afforded (1) in yields of 28-43%. Isomerization of the diphenol (25) with palladium(II) chloride bis ( acetonitrile ) in refluxing chloroform proceeds at a faster rate than the isomerization of (27), thereby affording the mono isomerized diphenol (38) in 37% yield. Methylation of (38) affords (37), a known precursor of (1).