초록
<P>A new type of cascade biocatalysis was developed for one-pot enantioselective conversion of a <I>meso</I>- or racemic epoxide to an α-hydroxy ketone in high ee via an epoxide hydrolase-catalyzed hydrolysis of the epoxide, an alcohol dehydrogenase-catalyzed oxidation of the diol intermediate, and an enzyme-catalyzed cofactor regeneration. In vitro cascade biotransformation of <I>meso</I>-epoxides (cyclopentene oxide <B>1a</B>, cyclohexene oxide <B>1b</B>, and cycloheptene oxide <B>1c</B>) was achieved with cell-free extracts containing recombinant SpEH (epoxide hydrolase from <I>Sphingomonas</I> sp. HXN-200), BDHA (butanediol dehydrogenase from <I>Bacillus subtilis</I> BGSC1A1), and LDH (lactate dehydrogenase form <I>Bacillus subtilis</I>) or NOX (NADH oxidase from <I>Lactobacillus brevis</I> DSM 20054), respectively, giving the corresponding (<I>R</I>)-α-hydroxycyclopentanone <B>3a</B>, (<I>R</I>)-α-hydroxycyclohexanone <B>3b</B>, and (<I>R</I>)-α-hydroxycycloheptanone <B>3c</B> in 98–99% ee and 70–50% conversion with TTN of NAD<SUP>+</SUP>-recycling of 5500–26 000. Cascade catalysis with mixed cells of <I>Escherichia coli</I> (SpEH) and <I>E. coli</I> (BDHA-NOX) converted 100–300 mM <I>meso</I>-epoxides <B>1a</B>–<B>1c</B> to (<I>R</I>)-α-hydroxy ketones <B>3a</B>–<B>3c</B> in 98–99% ee and 85–57% conversion. Cells of <I>E. coli</I> (SpEH-BDHA-NOX) coexpressing all three enzymes were also proven as good catalysts for the cascade conversion of 100–200 mM <I>meso</I>-epoxides <B>1a</B>–<B>1c</B>, giving (<I>R</I>)-α-hydroxy ketones <B>3a</B>–<B>3c</B> in 98–99% ee and 79–52% conversion. The cascade biocatalysis for one-pot synthesis of α-hydroxy ketone in high ee was also successfully demonstrated with a racemic epoxide (1,2,3,4-tetrahydronaphthalene-1,2-oxide <B>1d)</B> as the substrate. By using two whole-cells based approaches, (<I>R</I>)-α-hydroxytetralone <B>3d</B> was obtained in 99% ee and 49–40% conversion from 20 to 5 mM racemic epoxide <B>1d</B>. Preparative cascade biotransformation of cyclohexene oxide <B>1b</B> gave (<I>R</I>)-α-hydroxycyclohexanone <B>3b</B> in 98% ee with 70% isolated yield. The developed new type of cascade biocatalysis is enantioselective, green, and often high yielding. The concept might be generally applicable to produce other useful enantiopure α-hydroxy ketones from the corresponding <I>meso</I>- or racemic epoxides by cascade catalysis using appropriate enzymes.</P><P><B>Graphic Abstract</B><BR><IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/accacs/2015/accacs.2015.5.issue-1/cs5016113/production/images/medium/cs-2014-016113_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/cs5016113'>ACS Electronic Supporting Info</A></P>