| Autor: |
Yakovleva ED; RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation. vzaitsev@sci.pfu.edu.ru., Shelukho ER; RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation. vzaitsev@sci.pfu.edu.ru., Nadirova MA; RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation. vzaitsev@sci.pfu.edu.ru., Erokhin PP; RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation. vzaitsev@sci.pfu.edu.ru., Simakova DN; RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation. vzaitsev@sci.pfu.edu.ru., Khrustalev VN; RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation. vzaitsev@sci.pfu.edu.ru.; Zelinsky Institute of Organic Chemistry of RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation., Grigoriev MS; Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninsky pr. 31, bldg. 4, 119071, Moscow, Russian Federation., Novikov AP; RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation. vzaitsev@sci.pfu.edu.ru.; Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninsky pr. 31, bldg. 4, 119071, Moscow, Russian Federation., Romanycheva AA; Pharmaceutical Technology Transfer Center, Yaroslavl State Pedagogical University Named After K. D. Ushinsky, 108/1 Republican St., 150000, Yaroslavl, Russian Federation., Shetnev AA; Moscow Institute of Physics and Technology, 1 'A' Kerchenskaya st., 117303 Moscow, Russian Federation., Bychkova OP; Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russian Federation., Trenin AS; Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russian Federation., Zubkov FI; RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation. vzaitsev@sci.pfu.edu.ru., Zaytsev VP; RUDN University, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation. vzaitsev@sci.pfu.edu.ru. |
| Abstrakt: |
Thienylallylamines, readily accessible from the corresponding thienyl aldehydes, react with maleic and trifluoromethylmaleic anhydrides leading to the formation of acids with a thieno[2,3- f ]isoindole core. The reaction sequence involves two successive steps: acylation of the nitrogen atom of the initial allylamine and the intramolecular Diels-Alder vinylarene (IMDAV) reaction. The scope and limitations of the proposed method were thoroughly investigated. It has been revealed with the aid of X-ray analysis and DFT calculations that the key step, the IMDAV reaction, proceeds through an exo -transition state, giving rise to the exclusive formation of a single diastereomer of the target heterocycle. The obtained functionally substituted thieno[2,3- f ]isoindole carboxylic acids are potentially useful substrates for further transformations and bioscreening. The antimicrobial evaluation of the obtained compounds revealed that 1-oxo-2-(3-(trifluoromethyl)phenyl)hexahydrobenzo[4,5]thieno[2,3- f ]isoindole-10-carboxylic acid is the most active sample in the synthesized library. It exhibits antibacterial activity against sensitive strains of Gram-positive bacteria, including S. aureus , Enterococcus faecium , Bacillus cereus , and Micrococcus luteus , as well as the Gram-negative bacteria E. coli and Pseudomonas fluorescens , with MIC values ranging from 4 to 64 μg mL -1 . 9-Oxo-8-phenyloctahydronaphtho[2,1- d ]thieno[2,3- f ]isoindole-10-carboxylic acid showed antifungal activity against yeast culture C. albicans with a MIC value of 32 μM. |
