Synthesis of the AB-ring portion of lavendamycin analogs via the diels-alder condensation : an honors thesis (HONRS 499)

Abstract

Lavendamycin analogs have demonstrated potential as cancer-fighting agents but because of their high degree of toxicity and low solubility in pharmacological solvents, new analogs are required which will exhibit selective toxicity for tumor cells and also be soluble in solvents for administration as cancer-fighting drugs. The goal of this research is to produce an analog of Lavendamycin (1) with a high selective toxicity for ras oncogene transformed cells and low toxicity for normal healthy cells. This can be accomplished through structure-activity relationship studies on a series of lavendamycins. To provide the series of analogs to be used in the studies, means by which various analogs may be produced must be devised.The goal of this project is to synthesize the AB-ring portion of a 7-Nbutyryllavendamycin via a Diels-Alder condensation. The synthesis of 7-butyramido-2methyl-quinoline-5,8-dione (12) from the precursors 2-butyramido-6-bromobenzoquinone (6) and N-(O-t-butyldimethylsiloxy)-1-aza-2-methyl-1,3-butadiene (5) is the goal of this project. The Diels-Alder condensation is a general method for the production of a variety of quinolines and will lead to quinolines, which are substituted at the C-7 as well as the C-6 positions. The latter compounds are unavailable through our other synthetic schemes.