Synthesis, Mechanism Elucidation And Biological Insights Of Tellurium(Iv)-Containing Heterocycles

Inspired by the synthetic and biological potential of organotellurium substances, a series of five- and six-membered ring organotelluranes containing a Te-O bond were synthesized and characterized. Theoretical calculations elucidated the mechanism for the oxidation-cyclization processes involved in the formation of the heterocycles, consistent with chlorine transfer to hydroxy telluride, followed by a cyclization step with simultaneous formation of the new Te-O bond and deprotonation of the OH group. Moreover, theoretical calculations also indicated anti-diastereoisomers to be major products for two chirality center-containing compounds. Antileishmanial assays against Leishmania amazonensis promastigotes disclosed 1,2 lambda(4)-oxatellurane LQ50 (IC50=4.1 +/- 1.0; SI=12), 1,2 lambda(4)-oxatellurolane LQ04 (IC50=7.0 +/- 1.3; SI=7) and 1,2 lambda(4)-benzoxatellurole LQ56 (IC50=5.7 +/- 0.3; SI=6) as more powerful and more selective compounds than the reference, being up to four times more active. A stability study supported by Te-125 NMR analyses showed that these heterocycles do not suffer structural modifications in aqueous-organic media or at temperatures up to 65 degrees C.