Synthesis, mechanism elucidation and biological insights of tellurium(IV)-containing heterocycles

Leandro Piovan, João Pedro A. Souza, Pamela T. Bandeira, Leociley R. A. Menezes, Mateus B. Bespalhok, Débora B. Scariot, Francielle P. Garcia, Siddhartha O. K. Giese, David L. Hughes, Celso V. Nakamura, Andersson Barison, Alfredo R. M. Oliveira, Renan B. Campos

Research output: Contribution to journalArticlepeer-review

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 1,2λ 4-oxatellurane LQ50 (IC 50=4.1±1.0; SI=12), 1,2λ 4-oxatellurolane LQ04 (IC 50=7.0±1.3; SI=7) and 1,2λ 4-benzoxatellurole LQ56 (IC 50=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 125Te NMR analyses showed that these heterocycles do not suffer structural modifications in aqueous-organic media or at temperatures up to 65 °C.

Original languageEnglish
Pages (from-to)14427-14437
Number of pages11
JournalChemistry – A European Journal
Volume27
Issue number58
Early online date18 Aug 2021
DOIs
Publication statusPublished - 19 Oct 2021

Keywords

  • Te NMR spectroscopy
  • hypervalency
  • leishmania
  • oxidation–cyclization mechanism
  • tellurium

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