Kinetic resolution of phosphoric diester by Cinchona alkaloid derivatives provided with a guanidinium unit

Abstract

Cinchona alkaloid derivatives featuring a guanidinium group in diverse positions efficiently catalyze the cleavage of the RNA model compound 2-hydroxypropyl p-nitrophenyl phosphate (HPNP). Their high catalytic efficiency as phosphodiesterases and the potentiometric and kinetic investigations indicate the existence of a high degree of cooperation between the guanidinium group and the quinuclidine moiety with the operation of a general acid/general base mechanism. The performance of these compounds was investigated and compared in the kinetic resolution of HPNP. These data were also compared with the results of DFT calculations on the transition states of the transesterification reaction that, in part, predict and rationalize the experimental data.