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 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 HCl solution (pH 5.0) to generate the benzaldehyde group at the alpha-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 (1)H and (13)C 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(6)H(4)-).
Akiyama
Yoshitsugu
Y
Department of Materials Science, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Nagasaki
Yukio
Y
Kataoka
Kazunori
K
D001547:Benzaldehydes / Q000032:analysis / Q000138:chemical synthesis*; D004220:Disulfides / Q000032:analysis / Q000138:chemical synthesis; D005027:Ethylene Oxide / Q000032:analysis / Q000138:chemical synthesis*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011092:Polyethylene Glycols / Q000032:analysis / Q000138:chemical synthesis*; D011108:Polymers / Q000032:analysis / Q000138:chemical synthesis*
D001547:Benzaldehydes; D004220:Disulfides; D011108:Polymers; D011092:Polyethylene Glycols; D005027:Ethylene Oxide