Biotechnologia Acta Т. 16, No. 2 , 2023
P 7-10., Bibliography 10, Engl.
UDC: 577.29
DOI: https://doi.org/10.15407/biotech16.02.007

Full text: (PDF, in English) 

 SYNTHESIS OF CALIX[4]ARENES WITH FIXED CONFORMATION AS POTENTIAL INHIBITORS OF FIBRIN POLYMERIZATION

D.M. Ahishev ^{1, 2, 3}, O.O. Hrabovskyi ¹

¹Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, Kyiv;
² Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, Kyiv;
³ Kyiv National Taras Shevchenko University, Ukraine

Aim. The purpose of the present study was to develop a method for the fixation of ‘fixed’ conformation for estimation of the impact of calix[4]arene structure on the efficacy of its anticoagulant activity. This was achieved by substitution of the lower rim of C-145 analogue.

Methods.Calix[4]arene C-145F (compound 6) was obtained in 4 steps starting with Duff reaction. Calix[4]arene methylene-bis-phosphonic ester 3 was prepared via addition of diisopropylphosphite in presence of metallic sodium to the parent calix[4]arene aldehyde 2. Further steps included Mitsunobu reaction, that afforded dipropoxycalix[4]arene 5 with rather good yields (80%), following the hydrolysis step that resulted in compound 6 in almost quantitative yield.
Modeling of 3D-structure of calix[4]arene C-145 and its analogue C-145F was performed in Maestro, Schrodinger software.

Results. Using a 2D NMR-NOESY spectroscopy, we can observe a distinct cross-peak between an aromatic singlet with a chemical shift on 7.72 ppm and protons of isopropyl group with a chemical shift on 1.62 ppm, which are moved in the strong field.

Conclusions. The easy method of the fixation of conus conformation of calix[4]arene cup will be useful for synthesis of novel functionally active compounds. We believe that further development and study of different calix[4]arenes will help scientists to obtain bioactive molecules that could be prospective anti-thrombotic drugs.

Key words: calix[4]arene, fibrin polymerization, organic synthesis, bioinformatics.

© Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, 2023