Water-soluble cavitands: Synthesis of methylene-bridged resorcin[4]arenes containing hydroxyls and phosphates at their feet and bromomethyls and thiomethyls at their rims

The synthesis of rim-functionalized methylene-bridged resorcin[4]arenes ("cavitands") containing hydrophilic propanol or water-solublilizing propylphosphate feet is described. The cavitands possess the synthetically useful benzylthiol (cavitands 6 and 16) or benzylbromide (cavitands 9 and 11) functionalities at their rims, which are suitable for further derivatization near the hydrophobic cavity of the cavitand. These water-soluble cavitands represent new building blocks that are ideal for use in aqueous supramolecular chemistry. As an example of their synthetic utility in supramolecular studies, we have reacted phosphate-footed cavitands 11 and 16 with cysteine-containing peptide 17 and chloroacetylated peptide 19, respectively, to afford the corresponding de novo proteins 18 and 20.