Synthetic Studies of Kinamycin Antibiotics: Stereoselective Synthesis of the Highly Oxygenated D-Ring and Construction of the ABD-Ring System of Kinamycins

A concise and stereoselective synthesis of the highly oxygenated D-ring of the kinamycin family of antitumor antibiotics was achieved from commercially available 3-methyl-2-cyclohexen-1-one. The key steps included a regioselective isomerization of a cis-epoxy alcohol, a regioselective reductive ring opening of a benzylidene ketal, and a stereoselective -hydroxy-directed ketone reduction. The Ullmann coupling between a bromonaphthaldehyde AB-ring fragment and an -iodocyclohexenone, which is a versatile D-ring precursor, effected the construction of the functionalized ABD-ring system that may provide access to kinamycin F and its structural analogues.