Abstract

The devastating effects of cancer have been documented and researched for many centuries. The first lead to the treatment of various hematological and solid tumors was the discovery of cytotoxic antitumor drugs and the use of chemotherapy. One current cytotoxic antitumor drug of interest is combretastatin A-4 (CA-4). Research has found that CA-4 and other chalcone-based molecules have shown potential as antimitotic agents for use in cancer treatment. Previous studies have shown that specific analogs containing a trimethoxy A-ring, a cis-conformation and a para- methoxy B-ring have increased CA-4 binding at the tubulin-colchicine binding site. Other studies suggest that CA-4 analogs containing a triazole indole ring system have increased water solubility as well as cytotoxicity. Based on these findings a 2-(1,2,3-triazolyl)indole analog of CA-4 was designed containing the key features discussed. A multi-step synthetic scheme was followed starting with the synthesis of ethyl azidoacetate. Production of ethyl azidoacetate was achieved by an SN2 reaction of ethyl bromoacetate and sodium azide resulting in a 55% yield. The next step in the reaction scheme involved the use of 3-hydroxy-4-methoxybenzaldehyde. Due to the acidity of the hydroxyl group, a tetrahydropyran protecting group addition was achieved using pyridinium p-toluenesulfonate as a catalyst resulting in a 62 % yield. After producing the protected benzaldehyde, a reaction of protected aldehyde and ethyl azidoacetate generated a 25 % yield of crude vinyl azide. In future research the vinyl azide will undergo thermolysis via the Hemettsberger-Knittel indole synthesis involving a ring cyclization to produce an indole ring system.

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