Computational study of acylphloroglucinols: an investigation with many branches

Abstract

Abstract Acylphloroglucinols (ACPLs) are a broad class of compounds structurally derived from phloroglucinol and characterised by the presence of a CRO group. They are interesting for their biological activities and their potentialities as lead compounds in drug development. The current review considers a series of works which, altogether, sum up to a systematic computational study of ACPLs in vacuo and in three solvents – chloroform, acetonitrile and water. An initial set of studies, focusing on ACPLs as a class and utilising an adequately representative selection of molecules, identified patterns in the conformational preferences and molecular properties of ACPLs, which appear valid for the whole class or for specific subclasses such as monomeric ACPLs, dimeric ACPLs, ACPLs with substituents containing C=C double bonds, etc. The validity of the identified patterns was further verified through the study of additional and significantly different ACPL molecules, as well as other molecular structures containing ACPL units. Furthermore, the computational study of ACPLs proved interesting for the insights into the factors stabilising their conformers, first of all intramolecular hydrogen bonding, which plays dominant roles in determining conformational preferences and energetics. The current review outlines the objectives, approaches and main results of these studies. The obtained information may be relevant for further studies aimed at a better understanding of the molecular bases of the biological activities of ACPLs.