Versatile and selective synthesis of "click chemistry" compatible heterobifunctional poly(ethylene glycol)s possessing azide and alkyne functionalities.
Versatile route for "click chemistry" compatible heterobifunctional PEGs was established through preparation of alpha-tetrahydropyranyloxy-omega-hydroxyl poly(ethylene glycol) (THP-PEG-OH) via ring-opening polymerization of ethylene oxide using 2-(tetrahydro-2H-pyran-2-yloxy)ethanol as an initiator, followed by the functionalization of omega-OH group to either the azido or alkyne group. Quantitative azidation of THP-PEG-OH was confirmed from the analysis of molecular functionality of the derivatives. While the conversion efficiency of omega-alkynation was appropriately 70%, the unreacted THP-PEG-OH fraction was successfully removed by ion-exchange chromatography after the carboxylation of the hydroxyl group with succinic anhydride. Then, the protecting group of the alpha-end, THP, was removed in mild acidic media, followed by two- or three-step modification of the resulting alpha-hydroxyl group to primary amino or thiol groups. Consequently, "click chemistry" compatible heterobifunctional PEG derivatives (X-PEG-Y; X = NH(2) and SH, Y =Azide and Alkyne) were synthesized with high efficiency and controlled molecular weight.
Hiki
Shigehiro
S
Department of Materials Engineering, Graduate School of Engineering, and Center for NanoBio Integration, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Kataoka
Kazunori
K
D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000138:chemical synthesis* / Q000737:chemistry*; D005027:Ethylene Oxide / Q000737:chemistry; D006878:Hydroxides / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry*; D013379:Substrate Specificity
D000480:Alkynes; D001386:Azides; D003432:Cross-Linking Reagents; D006878:Hydroxides; D011092:Polyethylene Glycols; C031356:hydroxide ion; D005027:Ethylene Oxide