The Route Development Towards Dicytoquinazol A Analogs to Investigate Neuroprotective Activity Against Glutamate Excitotoxicity

Abstract

Multiple Sclerosis (MS) is a chronic neurological disease that impacts millions every year and cases continue to grow. A hypothesized mechanism that contributes to MS is glutamate excitotoxicity. A natural product shown to exhibit neuroprotective activity against glutamate excitotoxicity is Dictyoquinazol A. A route was developed to investigate the structural versatility of Dictyoquinazol A. The route consists of three key steps: an amide coupling reaction, a nitro group reduction, and an acid-catalyzed cyclization. The amide coupling reaction proved to be difficult. However, thionyl chloride (SOCl2) revealed to be a successful activating reagent for the synthesis of N-o-(Hydroxymethyl)phenyl5-methoxy-2-nitrobenzamide. However, SOCl2 left sulfur impurities in the nitrobenzamide that prevented the reduction of the nitro group. To avoid the problems presented by SOCl2, oxalyl chloride (CO2Cl2) served as another activating reagent that produced the nitrobenzamide. The successful synthesis can lead to the completion of the nitro group reduction and acid-catalyzed cyclization. The completion of the proposed route enables a model system for the synthesis of Dictyoquinazol A analogs. The synthesis of the analogs will promote the investigation of their structure and neuroprotective activity pertaining to glutamate excitotoxcity.