Synthetic approaches toward the aminoquinone natural product streptonigrin: Key C-ring functionalizations

ORGN 777

Frederick E. Nytko III, and Philip DeShong, Department of Chemistry and Biochemistry, The University of Maryland, Building 091 - Chemistry Building, College Park, MD 20740
Work has been undertaken toward the modular total synthesis of the antitumor natural product streptonigrin, beginning at the C-ring. Starting from the simple hydroxypyridone precursor, selective bromination of the 4-position hydroxyl group was achieved via phosphorus tribromide. Regiospecific oxidation, and subsequent esterification at the 6-position yielded the methyl ester, capable of withstanding the oxidizing conditions of mixed acid nitration to come later in the synthesis. Triflation of the pyridone carbonyl provided us with a selective Sonogashira coupling location for the o-nitroaryl propargyl alcohol AB-ring precursor, which has been shown by Sandelier to undergo cyclization to form quinolines and quinolones under reductive conditions. The general skeletal structure of the C-ring was completed upon nitration at the 2-position, followed by Suzuki coupling of the D-ring at the 4-position. The streamlined synthesis of the C-ring fragment achieved complex intermediates in reasonable yields, while aligning well for subsequent final transformations required to complete the total synthesis of the natural product.