The inhibition of HSP90 by drugs such as novobiocin has recently shown to be a potential cancer treatment pathway.  Formation of a novel azanovobiocin derivative with better inhibitory properties seemed possible through metal-catalyzed C-N bond formation with the use of the (cis)-N-(1-(2-bromophenyl)-3-(methylamino)-3-oxoprop-1-en-2-yl)benzamide starting material.  Both the CuTC-mediated, MW-assisted lactamization reactions and the Pd-catalyzed reflux lactamization reactions were performed with varying results.  Neither was successfully able to produce the azanovobiocin derivative, but major products that were formed from the CuTC reaction included novobiocin, the indo formation of the product with C-N bond formation, and an oxazoquinolone.  Products from the Pd-catalyzed reactions produced both a brominated and nonbrominated product that was either an azlactam formation or an isoquinoline formation.  Although neither reaction synthesized the expected products, future experiments should focus on CuTC in light of its more promising results.

Synthesis of azanovobiocin derivatives using Cu(I)/Pd(II)-catalyzed C-N bond formation

243rd National Meeting (2012)

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