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

摘要

New heterotelechelic PEG-containing benzaldehyde and 2-pyridyldithio endgroup(CHO-Bz-PEG-SSpyl) was synthesized with high efficiency and high selectivity.An a-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 omega-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 HC1 solution(pH 5.0)to generate the benzaldehyde group at the a-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=CHC_6H_4-).