SPOCC: A resin for solid-phase organic chemistry and enzymatic reactions on solid phase

SPOCC resin 1, a novel, highly permeable, polar support for chemical and en zymatic solid-phase methods, is presented. The synthesis of SPOCC resin is based on the cross-linking of long-chain poly(ethylene glycol) (PEG) termin ally substituted with oxetane by cationic ring-opening polymerization, affo rding a polymer containing only primary ether and alcohol C-O bonds. The po lymer was prepared using Et2O . BF3 as initiator either via bulk polymeriza tion in solution or via suspension polymerization in silicon oil, the latte r yielding a beaded resin. The polymerization reaction was investigated wit h respect to the effects of PEG chain length, the fraction of bisoxetanylat ed PEG, initiator amount, and temperature in order to vary the swelling, lo ading, and mechanical stability of the resin. Furthermore, the resin was de rivatized with various functional groups and subsequently applied to peptid e synthesis and organic reactions in both organic solvents and water. An N- terminal peptide aldehyde was generated on the solid phase and employed to synthesize peptide isosteres by nucleophilic addition of various ylides. So lid-phase glycosylation of peptides and enzymatic reactions were successful ly performed with SPOCC resin. Enzymatic proteolytic cleavage of a resin-bo und decapeptide on treatment with the 27 kDa protease subtilisin BNP' demon strated the accessibility of the interior of the SPOCC resin for enzymes.