Synthesis of tubastrine analogues as potential antifouling agents

Abstract

In recent years, several isolated natural products containing a guanidine group have proven to have antibacterial effects. Preparation of such molecules synthetically is therefore highly relevant for mitigation and control of biofouling. With reference to the guanidine natural product tubastrine, several pathways for syntheses of analogues was outlined and tested in this research project. The microwave assisted C-N cross coupling reaction reported by Lorentzen et al. (2015) was studied in detail and optimized from 49 to 67 %. Research was conducted on preparing para-alkylated starting materials for the same reaction and suitable conditions for selective para-alkylation was determined. A maximum of 73 % selective para-alkylation was observed.

In addition, syntheses of analogues with differences in the main molecular structure was tested. Attempts were made to synthesize an analogue with one additional carbon between the aromatic ring and the guanidine group via amide to amine reduction. Reduction of the amide was not successful. Furthermore, reactions utilizing the natural product dopamine was tested for synthesis of an analogue without the olefinic chain found in tubastrine. Dopamine reacted with the required solvent DMF and produced the corresponding amide.

Finally, synthesis of an amidine analogue of tubastrine was tested using Meerwein’s reagent. The amidine analogue was produced in 58 % yield.