Synthetic studies on kinamycin antibiotics

Abstract

This thesis entails a strategy for the synthesis of the kinamycin family of antitumor antibiotics and its structural analogues, where a concise and stereoselective synthesis of the highly oxygenated D-ring as well as the construction of the ABD-ring system of kinamycins was achieved. Access to the highly oxygenated D-ring was provided from commercially available 3-methylcyclohexen-2-one, with key steps including a regioselective isomerization of a cis-epoxyalcohol, a regioselective reductive opening of a benzylidene ketal and a stereoselective α-hydroxy directed ketone reduction.Model studies indicated that the assembly of the ABD-ring system of kinamycins was feasible via a metal-catalyzed Ullmann coupling reaction strategy. Indeed, coupling of a highly oxygenated cyclohexenone D-ring with a bromonaphthaldehyde AB-ring fragment, gave access to a highly functionalized kinamycin ABD-ring intermediate that may provide access to kinamycin F and its structural analogs.Furthermore, the chemistry that was developed here may be amenable to asymmetric synthesis and provide access to optically active material.