Model structures for the study of acylated phloroglucinols and computational study of the caespitate molecule

Acylated phloroglucinols are widely spread in nature. Many of them exhibit biological activities, and the natural materials in which they are found have been used in traditional medicine. However, theoretical studies on phloroglucinols are rare, and they have mostly concerned the parent compound, 1,3,5-trihydroxybenzene. In the current work, the influence, on conformational preferences and energy, of the intramolecular hydrogen bond engaging the oxygen atom of the carbonyl group characterising acylated phloroglucinols, and of the geometrical features of the phloroglucinol skeleton, is investigated on four model structures, selected in such a way as to cover all the aspects of interest. All the possible geometrical options for each of these structures were calculated and compared. The results show a preference for the H-bond to form on the same side of a second substituent chain (when present) and the influence of the various aspects of the orientation of the OH groups. These results can constitute a reference for the study of acylated phloroglucinols in general and, more specifically, of acylated phloroglucinols having a second substituent chain besides the acyl chain, as confirmed by the study of the caespitate molecule, an acylated and prenylated phloroglucinol whose prenyl chain ends with an acetic-acid ester group. The presence of the ester function enables the formation of a second intramolecular H-bond with a variety of different geometries for the resulting ring, and conformers with both intramolecular H-bonds account for practically the total population. All the calculations were performed at HF level with the 6-31-G(d,p) basis set. The performance of AM1 and PM3 semiempirical methods was also investigated and found not completely adequate.