BN/CC Isosteric Compounds as Enzyme Inhibitors: N- and B-Ethyl-1,2-azaborine Inhibit Ethylbenzene Hydroxylation as Nonconvertible Substrate Analogues


  • We acknowledge the financial support of the priority program 1319 of the German Research Foundation (DFG), the excellence program LOEWE/Synmikro from the state of Hessen, the Polish Ministry of Science and Higher Education under the grant N N204 269038 and MNiSW/SGI3700/PAN/121/2006. Support for this research has been provided by the National Institutes of Health (Grant R01-GM094541). Support for G.P.H has been provided by the Arnold and Mabel Beckman Foundation and the Camille & Henry Dreyfus Foundation. We thank Jesse Jenkins for some early synthetic contributions.


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Good substrate gone bad! BN/CC isosterism of ethylbenzene leads to N-ethyl-1,2-azaborine and B-ethyl-1,2-azaborine. In contrast to ethylbenzene, which is the substrate for ethylbenzene dehydrogenase (EbDH), N-ethyl-1,2-azaborine (see scheme; Fc=Ferricenium tetrafluoroborate) and B-ethyl-1,2-azaborine are strong inhibitors of EbDH. Thus, the changes provided by BN/CC isosterism can lead to new biochemical reactivity.