Easy Separation of Optically Active Secondary Alcohols by Enzymatic Hydrolysis of Soluble Polymer-Supported Carbonates

Abstract

Abstract The enzyme-mediated enantioselective hydrolysis of middle molecular weight poly(ethylene glycol) (PEG)-supported carbonates is disclosed. The representative water-soluble substrate was prepared by the immobilization of (±)-1-phenylethanol onto a monomethoxy PEG (MPEG, av. Mw 5000) or PEG (av. Mw 4600) through a carbonate linker. Porcine pancreas lipase (PPL) enantioselectively catalyzed the hydrolysis of the polymer-supported substrate in a mixed solvent (hexane/buffer = 9/1) at 0 °C to afford the corresponding optically active compounds. In this system, the separation of the remaining (S)-substrate and the resulting (R)-alcohol was achieved by a simple procedure without any laborious column chromatography. The substrate was easily hydrolyzed with NaOH in MeOH–H2O to give the (S)-alcohol. This procedure was also applicable to the preparation of other optically active secondary alcohols. As expected, an introduction of a hydrophobic spacer between the MPEG moiety and the carbonate linker affected both the reactivity and enantioselectivity. An o-substitution produced a lower conversion than those of the reaction of the m- and p-substituted substrates. While the substrate with a p-phenylethyl spacer gave the best E value (>200) with low conversion, the reaction of the substrate with a p-phenylmethyl spacer smoothly proceeded with high enantioselectivity (E value = 151).