Polycyclic ferrocenyl(dihydro)thiazepine derivatives: Diastereo-selective synthesis, characterization, electrochemical behavior, theoretical and biological investigation
Por:
Sanchez Garcia, Jessica J., Toledano-Magana, Yanis, Flores-Alamo, Marcos, Martinez-Klimova, Elena, Galindo-Murillo, Rodrigo, Hernandez-Ayala, Luis F., Ortiz-Frade, Luis, Garcia-Ramos, Juan C.
Publicada:
1 ene 2017
Resumen:
The reaction of E-2-ferrocenylmethylidenetetralones and
E,E-2,6-bis-(ferrocenylmethylidene)-cyclohexanone with 2-aminothiophenol
proceed with high diastereoselectivity, forming the similar to 4.5:1
mixture of trans- and cis-isomers of polycyclic ferrocenylthiazepines,
respectively. The reactions of
E,E-2,5-bis-(ferrocenylmethylidene)cyclopentanone and
E,E-3,5-bis-(ferrocenylmethylidene)-1-methyl-4-piperidone with
2-aminothiophenol take place stereo specifically to form the
diastereomeric tricyclic thiazepines of cis- and trans configuration,
respectively. The structures of the obtained compounds were established
by IR, H-1 and C-13 NMR spectroscopy and mass-spectrometry. The
structures of the trans-tetralino[1,2a]-,
trans-5,7-dimethyltetralino[1,2a]-2ferrocenyl-
[1,5]benzo-2,3-dihydrothiazepines and
cis-5-ferrocenyl-methylidenecyclopentano[1,2a]-2-ferrocenyl-[1,5]ben
zo-2,3-dihydrothiazepine were confirmed by X-ray diffraction analysis.
An electrochemical study reveals that the diferrocenyl derivatives
belong to a Class I compounds of the Robin-Day classification. This
behavior is explained by the analysis of frontier orbitals as calculated
by density functional theory, showing that only one ferrocenyl unit
participates in the generation of HOMO and LUMO orbitals. Compounds 4a
and 4c showed similar capacity to inhibit the proliferation of HM1: IMSS
trophozoite cultures than the first choice drug for human amoebiasis
treatment, metronidazole. Morphological changes induced in the
trophozoites after drug exposure suggest a redox in balance as the
probable mechanism of the parasite death. (C) 2016 Elsevier Inc. All
rights reserved.
Filiaciones:
Univ Nacl Autonoma Mexico, Fac Quim, Mexico City 04510, DF, Mexico
Univ Utah, Coll Pharm, Dept Med Chem, Salt Lake City, UT 84112 USA
Ctr Invest & Desarrollo Tecnol Electroquim, Dept Electroquim, SC, Queretaro 76703, Mexico
Univ Nacl Autonoma Mexico, Inst Quim, Dept Fisicoquim, Mexico City 04510, DF, Mexico
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