Synthesis of Heterotelechelic Poly(ethylene glycol) Derivatives Having (alpha)-Benzaldehyde and (omega)-Pyridyl Disulfide Groups by Ring Opening Polymerization of Ethylene Oxide Using 4-(Diethoxymethyl)benzyl Alkoxide as a Novel Initiator

New heterotelechelic PEG-containing benzaldehyde and 2-pyridyldithio endgroup (CHO-Bz-PEG-SSpyl) was synthesized with high efficiency and high selectivity. An (alpha)-benzylacetal-(omega)-methansulfonyl PEG was prepared as the first step to CHO-Bz-PEG-SSpyl through the ring-opening polymerization of ethylene oxide (EO) initiated by potassium 4(diethoxymethyl)benzyl alkoxide (PDA), followed by the successive conversion of the end-alkoxide group to a methanesulfonyl group and then to dithiocarbonate derivative. Further, deprotection of the dithiocarbonate derivative and subsequent conversion to the 2-pyridyldithio group at the (alpha)-end was successfully performed through a one-step reaction to form (alpha)-benzylacetal-(omega)-2-pyridyldithio PEG (aceBz-PEG-SSpyl). The aceBz-PEG-SSpyl was then treated with an aqueous HCl solution (pH 5.0) to generate the benzaldehyde group at the (omega)-end. Molecular functionalities of the benzaldehyde and the 2-pyridyldithio end group of the heterotelechelic PEG (CHO-Bz-PEG-SSpyl) thus prepared were characterized by 1H and 13C NMR, showing that the reaction proceeded almost quantitatively. The benzaldehyde end group is available to conjugate various ligands having a primary amino group by forming the pH-sensitive imine linkage (N=CHC6H4-).