SYNTHESIS OF AMINO-1-ADAMANTANE-BASED SOME DIPEPTIDES BY MULTICOMPONENT UGI-REACTION AND ITS PHYSICOCHEMICAL STUDY

Author: Kakha Davitashvili
Co-authors: Kakha Davitashvili, Tamar Tabatadze, Tinatin Bukia
Keywords: Amantadine, Dipeptide, Amino-1-adamantane, Isonitrile, Ugi-4CR
Annotation:

Amine-1-adamantane (Amantadine) is a broad-spectrum medication used (Gocovri, Symadine, Symmetrel, Memantine) to treat dyskinesia (associated with parkinsonism), influenza virus, and hepatitis. The efficacy of amantadine has been demonstrated against the Covid19 virus in combination with the drug chloroquine. Studies have shown that people with Parkinson’s disease who were on amantadine treatment and have tested positive for coronavirus did not show clinical manifestations of the disease. Amine-1-adamantane is a drug whose therapeutic indications are divided into 3 specialities: Neurology, Psychiatry, and Infectiology. It began to be used as a drug for humans in 1969 as a corrective medication for involuntary movement disorders and soon began to be used by psychiatry to control undesirable side effects caused by antipsychotic drugs (neuroleptics) and in neurology for the treatment of movement disorders, particularly Parkinson’s disease. The present study deals with the synthesis of new biologically active dipeptides based on amino-1-adamantane by multicomponent Ugi reaction and their physico-chemical study. Multicomponent Ugi reaction is a reaction between four or more reactive components based on isocyanides. This reaction makes it possible to obtain alpha-amino acid fragment containing dipeptides compatible with the human body. Isocyanides, carboxylic acids, amines and oxo compounds are used as reactive components. The reaction is distinguished by its flexibility and diversity, and due to the properties of the reacting groups, it is possible to obtain a variety of analogues in nature, the formation of which by known methods of synthesis is a long process or does not take place at all. The reaction was performed using (1) amino-1-adamantane, (2) isobutyl aldehyde, (3) 4-methoxy benzoic acid, and (4) ethylisocyanoacetate in methanol at 40 ° C for 72 h. The reaction was monitored by thin-layer chromatography (eluent hexane / ethyl acetate, 2/1 ratio mixture). After completion of the reaction, CH2Cl2 was added to the reaction mixture and treated first with 1 molar solution of NaHCO3 and then with 1 molar solution of KHSO4. Rinse the organic phase with a saturated aqueous solution of NaCl, and concentrate on a rotary evaporator. The obtained technical product was purified by the standard method of column chromatography (SiO2, petroleum/ethyl acetate). The molecular structure of the synthesized compounds was established by spectroscopy analysis, including IR and 1H, 13C NMR. Studies on synthesized compounds are ongoing.

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