Synthesis, Mechanism Elucidation and Biological Insights of Tellurium(IV)-Containing Heterocycles

Abstract

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 1,2λ⁴ -oxatellurane LQ50 (IC₅₀ =4.1±1.0; SI=12), 1,2λ⁴ -oxatellurolane LQ04 (IC₅₀ =7.0±1.3; SI=7) and 1,2λ⁴ -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 ¹²⁵ Te NMR analyses showed that these heterocycles do not suffer structural modifications in aqueous-organic media or at temperatures up to 65 °C.

Keywords: 125Te NMR spectroscopy; hypervalency; leishmania; oxidation-cyclization mechanism; tellurium.