TY - JOUR AU - Kronister, Stefan; Svatunek, Dennis; Denk, Christoph; Mikula, Hannes TI - Acylation-Mediated ‘Kinetic Turn-On’ of 3-Amino-1,2,4,5-tetrazines SN - 0936-5214 SN - 1437-2096 PY - 2018 JO - Synlett JF - Synlett LA - EN VL - 29 IS - 10 SP - 1297 EP - 1302 ET - 2018/02/16 DA - 2018/05/30 KW - click chemistry KW - tetrazines KW - kinetics KW - bioorthogonal chemistry KW - Diels–Alder reaction KW - acylation AB - The fast and biocompatible ligation of 1,2,4,5-tetrazines with strained alkenes has found numerous applications in biomedical sciences. The reactivity of a 1,2,4,5-tetrazine can generally be tuned by changing its electronic properties by varying the substituents in the 3- and/or 6-position. An increased reactivity of such bioorthogonal probes upon conjugation or attachment to a target molecule has not previously been described. Such an approach would be beneficial, as it would minimize the impact of residual tetrazine reagents and/or impurities. Herein, we describe such a ‘kinetic turn-on’ of 1,2,4,5-tetrazines upon conjugation. On the basis of the significant increase in reactivity following N-acylation predicted by quantum chemical calculations, we prepared 3-aminotetrazines and their corresponding acetylated derivatives. An investigation of the reaction kinetics indeed revealed a remarkable increase in reactivity upon acylation. PB - © Georg Thieme Verlag DO - 10.1055/s-0036-1591764 UR - http://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0036-1591764 ER -