2015 REU Poster: Cyathane Inspired Scaffold Synthesis in Flow

Abstract

Cyathane natural products were proven biologically relevant molecules as they stimulate the expression of NGF. As such some cyathanes are potential therapeutic agents for Alzheimer’s disease. A preliminary pharmacophore model was produced which consists of a simplified seven-six bicyclic molecular scaffold. A synthetic route could utilize the Buchner reaction, but until this time only unsubstituted, carbonyl stabilized diazo compounds have been used due to the explosive nature of other diazo species. Such a bicyclic compound would require further modification to remove the carbonyl functional group. Flow chemistry was utilized to overcome these restrictions with the Buchner Reaction. 1-(4-diazopentyl)-2-methoxybenzene was used as the model substrate, and numerous electronic and substitution analogs were synthesized to further expand the scope of the Buchner Reaction in flow. Optimizing the flow reaction to use unprotected hydrazine to form a free hydrazone intermediate in situ was also explored. The (5-(2-methoxyphenyl)pentan-2-yl) hydrazone was successfully formed, while further results are yet pending.