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An Efficient Method for the Conjugation of Hydrophilic and Hydrophobic Components by Solid‐Phase‐Assisted Disulfide Ligation
Author(s) -
Muguruma Kyohei,
Shirasaka Takuya,
Akiyama Daichi,
Fukumoto Kentarou,
Taguchi Akihiro,
Takayama Kentaro,
Taniguchi Atsuhiko,
Hayashi Yoshio
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201712324
Subject(s) - solubility , conjugate , solvent , chemistry , molecule , phase (matter) , aqueous solution , combinatorial chemistry , organic chemistry , chemical engineering , mathematical analysis , mathematics , engineering
Chemical conjugation between hydrophilic and hydrophobic components is difficult because of their extremely different solubility. Herein, we report a new versatile method with a solid‐phase‐assisted disulfide ligation to overcome the difficulty of conjugation attributed to solubility. The method involves two steps in a one‐pot process: 1) loading of a hydrophobic molecule onto a resin in an organic solvent, and 2) release of the solid‐supported hydrophobic molecule as a conjugate with a hydrophilic molecule into an aqueous solvent. This strategy allows the use of a suitable solvent system for the substrates in each step. Conjugates of a water‐insoluble drug, plinabulin, with hydrophilic carriers that could not be prepared by solution‐phase reactions were obtained in moderate yields (29–45 %). This strategy is widely applicable to the conjugation of compounds with solubility problems.