Towards peptide isostere libraries: aqueous aldol reactions on hydrophilicsolid supports

Polar polyoxyethylene-polyoxypropylene (POEPOP) resin was derivatised with a 4-hydroxymethyl phenoxy linker and used as a solid support for lanthanide triflate catalysed Mukaiyama type solid phase aldol reactions. The conditi ons were optimised using resin bound 4-alkoxybenzaldehyde and it was shown that use of an aqueous solvent was crucial. Also, the reactions were perfor med with an N-terminal peptide aldehyde substrate in very high yields. POEP OP resins prepared with different monomer chain lengths and commercially av ailable PEG-grafted NovaSyn TG resin were compared in the reactions.