α-(Imino)pyridyldifluoroethyl Phosphonates: Novel Promising Building Blocks in Synthesis of Biorelevant Aminophosphonic Acids Derivatives

Oksana Shavrina,Yuliya Rassukana,Petro Onys’Ko,Lyudmyla Bezgubenko,Andrii Bezdudny

doi:10.3390/org2020007

Abstract

A convenient synthetic approach to previously unknown NH-iminophosphonates bearing 2-, 3-, and 4-pyridyldifluoromethyl groups at the imine carbon atom was developed. The synthetic potential of these novel building blocks was demonstrated by their conversion into highly functionalized acyclic and heterocyclic aminophosphonates and phosphonic acids combining in their structure biorelevant aminophosphonic fragment, difluoromethyl group, and pyridyl, piperidyl, thiazolidin-4-one, or thiazidinan-4-one heterocyclic moieties in a single molecular platform.

Highlights

In the present work we report the synthesis of NH-iminophosphonates bearing α, β, or γ-pyridyldifluoromethyl group at the imine carbon atom and their use for the preparation of aminophosphonic acids derivatives bearing difluoromethyl group and heterocyclic residue
Analysis of theAnalysis literature shows that hydrophosphoryl compounds can react withcan react with compounds ofdata the literature data shows that hydrophosphoryl nitriles by different schemes
We have found that all three three isomeric pyridyldifluoroacetonitriles pyridyldifluoroacetonitriles

Summary

Introduction

Α-Aminophosphonates are phosphorus analogs of amino acids in which the planar carboxylic group is replaced with a tetrahedral bioisosteric phosphonic unit. They exhibit a wide range of biological activity and play a significant role in the development of antibiotics, antiviral, antihypertensive, antitumor agents and other bioactive substances [1,2,3,4,5]. Modification of organic molecule with fluorine has become almost a standard tool in modern drug design. It is generally accepted that introduction of a fluorine containing group may improve the pharmacodynamic and the pharmacokinetic profiles of the compound by concomitant alteration of its electronic, lipohilic, and steric characteristics as well as its metabolic stability [6,7,8,9]

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Results

Conclusion