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An Efficient Method for the Conjugation of Hydrophilic and Hydrophobic Components by Solid-Phase-Assisted Disulfide
Kyohei Muguruma1, Takuya Shirasaka1, Daichi Akiyama1
1Department of Medicinal Chemistry, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
Abstract:
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.
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