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

Muriel Albalat (1) , Gérard Audran (2) , Maxence Holzritter (2) , Sylvain R.A. Marque (2) , Philippe Mellet (3, 4) , Nicolas Vanthuyne (1) , Pierre Voisin (3)

1 ISM2 - Institut des Sciences Moléculaires de Marseille
2 ICR - Institut de Chimie Radicalaire
3 CRMSB - Centre de résonance magnétique des systèmes biologiques
4 INSERM - Institut National de la Santé et de la Recherche Médicale

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 CON 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 CON 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 CON bond homolysis. † Electronic supplementary information (ESI) available: Experimental procedures, analysis data, kinetics, LFER analysis and XRD data are reported as ESI. CCDC 1989155. For ESI and crystallographic data in CIF or other electronic format see

Domains: Chemical Sciences

Muriel Albalat, Gérard Audran, Maxence Holzritter, Sylvain R.A. Marque, Philippe Mellet, et al.. An enzymatic acetal/hemiacetal conversion for the physiological temperature activation of the alkoxyamine C–ON bond homolysis. Organic Chemistry Frontiers, 2020, 7 (19), pp.2916 - 2924. ⟨10.1039/d0qo00559b⟩. ⟨hal-03178449⟩