An enzymatic acetal/hemiacetal conversion for the physiological temperature activation of the alkoxyamine C–ON bond homolysis

Abstract

The potential of alkoxyamines as theranostic agents has been recently promoted by our groups. The success of such an approach relies on the switch upon enzymatic triggering between highly stable precursor alkoxyamines and activated alkoxyamines exhibiting fast homolysis of the C–ON bond. Hence, at 37 °C in water, benzyl 2-(2,2,6,6-tetramethylpiperidin-N-oxy)-3-ethoxy-3-acetoxypropanoate and benzyl 2-ditert-butylaminoxy-3-ethoxy-3-acetoxy propanoate afford t_max of 2000 s (35% conversion) and 500 s (60% conversion), respectively, for the C–ON bond homolysis in the presence of Subtilisin A whereas t_1/2 of ca. 42 thousand millenniums and 330 years are expected accordingly to E_a values in n-propanol. These results nicely highlight the on/off switch, provided that an enzymatic activity controls the C–ON bond homolysis.