Relationships between chemical structure and biting deterrency of the folk remedy repellent constituent, callicarpenal

Previous investigations by the authors identified callicarpenal (13,14,15,16-tetranor-3-cleroden-12-al) as one of the constituents responsible for the insect repellency in the folk remedy plant, Callicarpa americana. Specifically, callicarpenal demonstrated significant mosquito bite-deterring activity against Aedes aegypti and Anopheles stephensi, in addition to repellent activity against host-seeking nymphs of the blacklegged tick, Ixodes scapularis. In the present study, structural modifications were performed on callicarpenal in an effort to understand the functional groups necessary for maintaining and/or increasing its activity and to possibly lead to more effective insect control agents. Initial modifications in this study targeted the C-12 aldehyde or the C-3 olefin functionalities or combinations thereof. Mosquito biting deterrency appeared to be influenced most by C-3 olefin modification as evidenced by catalytic hydrogenation that resulted in a compound having significantly less effectiveness than callicarpenal at a test amount of 25 nmoles/cm2. Oxidation and/or reduction of the C-12 aldehyde did not diminish mosquito biting deterrency, but at the same time, none of the modifications were more effective than callicarpenal in deterring mosquito biting. Stereochemical modifications will also be discussed.