TY - JOUR
T1 - Synthesis, mechanism elucidation and biological insights of tellurium(IV)-containing heterocycles
AU - Piovan, Leandro
AU - Souza, João Pedro A.
AU - Bandeira, Pamela T.
AU - Menezes, Leociley R. A.
AU - Bespalhok, Mateus B.
AU - Scariot, Débora B.
AU - Garcia, Francielle P.
AU - Giese, Siddhartha O. K.
AU - Hughes, David L.
AU - Nakamura, Celso V.
AU - Barison, Andersson
AU - Oliveira, Alfredo R. M.
AU - Campos, Renan B.
N1 - Funding Information:
The authors thank the National Council for Scientific and Technological Development (CNPq, Brazil), and the Coordination for the Improvement of Higher Level Personnel (CAPES, Brazil) for financial support and fellowships of J.P.A.S., P.T.B., L.R.A.M., M.B.B., D.B.S., F.P.G., D.L.H. and S.O.K.G..
PY - 2021/10/19
Y1 - 2021/10/19
N2 - 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.
AB - 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.
KW - Te NMR spectroscopy
KW - hypervalency
KW - leishmania
KW - oxidation–cyclization mechanism
KW - tellurium
UR - http://www.scopus.com/inward/record.url?scp=85115325760&partnerID=8YFLogxK
U2 - 10.1002/chem.202102287
DO - 10.1002/chem.202102287
M3 - Article
VL - 27
SP - 14427
EP - 14437
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 58
ER -