Synthesis of an organocatalysis activated fluorophore compound and the evaluation of its organocatalytic action

Abstract

Signal transduction is a rudimentary and specific way of communication in cells, in which a signal triggers a specific response. However, mimicking these processes in organic materials has been a major challenge. Although, some organocatalysts have been shown to be responsive to specific signals, only limited research has been done using organocatalysis in biological systems. A potentially bio-compatible organocatalytic reaction is the DABCO catalysed nucleophilic substitution reaction of a vinylphosphonate with N- and S- terminal nucleophiles. To evaluate the bio-compatibility of the catalytic reaction, this study focused on the preparation of a catalytic active profluorophore. Hereby, the profluorophore becomes active (fluorescent) upon catalysis in the presence of cells. To do so, 7-amino-4-methyl-3-coumarinylacetic acid and 7-amino-1-methylquinolin-1-ium will be synthetically quenched by acetyl amide formation and are thereafter linked to the catalytic active component (3-hydroxyprop-1-en-2-ylphosphonate). Signals, such as amides and thiols can be used to trigger the reaction and hence releasing the quenched fluorophore.

7-amino-4-methyl-3-coumarinylacetic acid was successfully quenched using ethyl chloroformate, however transesterification of the catalytic active compound could not be achieved at various conditions. 7-amino-1-methylquinolin-1-ium was synthesised according to literature and compared to a reference, confirming the compound. Many attempts have been undertaken to further modify the fluorophore with the catalytic compound. Unfortunately, non of the proposed synthetic pathways, such as quenching with ethyl chloroformate, resulted in the envisioned product. Based on the obtained results, it is recommended to explore other synthetic strategies such as the usage of disuccinimidyl carbonate to quench the fluorophores.