AP19677249 - «Creation new functionally substituted framework phosphonates symmetric and asymmetric type, potentially active in treatment of various animal and human diseases»

 

Names of priority and specialized scientific areas:

Scientific research in the field of natural sciences. Fundamental and applied research in the field of chemistry.

The amount of financing

90 051 560  tg

Purpose

The goal of the project is to develop a strategy for creating new types of functionally substituted framework phosphonates of symmetrical and asymmetrical types, based on new reactions: 1) “one-pot” reaction of functionally substituted phenols with 2-ethoxyvinyl dichlorophosphonate; 2) reactions of phosphorinin derivatives with functionally substituted phenols, resulting in asymmetric phosphonates as a result of cyclization of the intermediate phosphaneoflavonoid.

Project objectives

Study the reaction of phenols containing an aldehyde, carboxylic, sulfonate, halomethyl group with 2-ethoxyvinyl dichlorophosphonate in order to obtain new functionally substituted framework phosphonates of a symmetrical type, elucidation of the role of trifluoroacetic acid on the synthetic result of the reaction, optimization of experimental conditions for the reactions.

Study the reaction of phosphorinin derivatives (phosphacoumarin) with functionally substituted phenols (containing a terminal carbonyl, carboxyl group), as well as with various dihydroxynafol derivatives, with the aim of synthesizing an intermediate neophosphaflavonoid. Optimization of experimental reaction conditions, study of the influence of the amount of trifluoroacetic acid and other acid catalysts, including Lewis acids, on the synthetic result of the reaction.

Study of the cyclization of intermediate neophosphaflavonoids containing terminal functional groups, which will be obtained as a result of the implementation of this project with the aim of synthesizing functionally substituted framework phosphonates of an asymmetrical type. Identification of the patterns of cyclization, the influence of the structure of the intermediate compound, experimental conditions - catalyst, solvent, temperature on the yield of an unsymmetrical frame phosphonate.

Study of reactions of the obtained functionally substituted framework phosphonates with NH-nucleophiles (hydrazines, hydrazides of carboxylic acids), including reactions with the anti-tuberculosis drug isoniazid, triphenylphosphine in order to obtain new types of structures that can exhibit high antimicrobial and antitumor activity. Synthesis of new derivatives of framework phosphonates of symmetrical and asymmetrical types, containing known pharmacophoric fragments. Optimization of experimental conditions, allowing to obtain these compounds in high yields and chemical purity, which is important for their further promotion as medicines.

Study of antimicrobial activity and cytotoxicity of the obtained compounds.

Expected results

In result, the reactions of 2-ethoxyvinyl dichlorophosphonate with functionally substituted phenols: 2,4-dihydroxybenzaldehyde, 2,4-dihydroxy-3-methylbenzaldehyde, 2,4-dihydroxybenzoic acid, in the presence of trifluoroacetic acid as a solvent, will be studied.

The influence of reaction conditions (the amount of trifluoroacetic acid used in relation to other reaction participants, temperature) on its synthetic result will be established, and the influence of the phenol structure on the course of the process will be revealed. Based on the data obtained, the most optimal reaction conditions will be selected to ensure the highest yield of target compounds.

The reactions of phosphorinin derivatives (phosphacoumarin) with functionally substituted phenols will also be studied: 2,4-dihydroxybenzaldehyde, 2,4-dihydroxy-3-methylbenzaldehyde, 2,4-dihydroxybenzoic acid, 6-hydroxy-2-naphthoic acid, as well as with various dihydroxynaphthol derivatives, in the presence of trifluoroacetic acid as a solvent.

The influence of reaction conditions (the amount of trifluoroacetic acid used in relation to other participants in the reaction, temperature) on its synthetic result will be revealed, and the influence of the nature of phenol on the course of this reaction will be revealed. Based on the data obtained, the most optimal reaction conditions will be selected to ensure the highest yield of target compounds. As a result of the work carried out, the first examples of neophosphaflavonoids will be obtained - intermediate products for the synthesis of functionally substituted unsymmetrical framework phosphonates.

Implementation period

2023 - 2025 у