Highly Efficient Synthesis of Monodisperse Poly(ethylene glycols) and Derivatives through Macrocyclization of Oligo(ethylene glycols)

Abstract A macrocyclic sulfate (MCS)‐based approach to monodisperse poly(ethylene glycols) (M‐PEGs) and their monofunctionalized derivatives has been developed. Macrocyclization of oligo(ethylene glycols) (OEGs) provides MCS (up to a 62‐membered macrocycle) as versatile precursors for a range of monofunctionalized M‐PEGs. Through iterative nucleophilic ring‐opening reactions of MCS without performing group protection and activation, a series of M‐PEGs, including the unprecedented 64‐mer (2850 Da), can be readily prepared. Synthetic simplicity coupled with versatility of this new strategy may pave the way for broader applications of M‐PEGs.