Asymmetric reduction of ethynyl ketones and ethynylketoesters by secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus

Secondary alcohol dehydrogenase (SADH) from Thermoanaerobacter ethanolicus, an NADP-dependent, thermostable oxidoreductase, reduces ethynyl ketones and ethynylketoesters enantioselectively to the corresponding propargyl (propargyl = prop-2-ynyl) alcohols. Ethynyl ketones, in general, are reduced with moderate enantioselectivity (with the exception of 4-methylpent-1-yn-3-one, which gives the (S)-alcohol with >98% ee). Although ethynyl ketones bearing a small (up to n-propyl) alkyl substituent are reduced to (S)-alcohols, larger ethynyl ketones give (R)-alcohols. In contrast, ethynylketoesters are converted to (R)-ethynylhydroxyesters of excellent optical purity. Unexpectedly, isopropyl ethynylketoesters give higher chemical yields and higher enantioselectivities of ethynylhydroxyesters than methyl or ethyl ethynylketoesters. The optically pure ethynylhydroxyesters may serve as useful chiral building blocks for asymmetric synthesis.

[1]  M. Martinelli,et al.  New Approach for the General Synthesis of Oxotetrahydroindoles via Intramolecular Cycloadditions of Azomethine Ylides with Tethered Alkynes , 1997 .

[2]  C. Vieille,et al.  Cloning and expression of the gene encoding the Thermoanaerobacter ethanolicus 39E secondary-alcohol dehydrogenase and biochemical characterization of the enzyme. , 1996, The Biochemical journal.

[3]  R. Phillips,et al.  Asymmetric reduction of aliphatic and cyclic ketones with secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus: effects of substrate , 1994 .

[4]  J. Zeikus,et al.  Purification of acetaldehyde dehydrogenase and alcohol dehydrogenases from Thermoanaerobacter ethanolicus 39E and characterization of the secondary-alcohol dehydrogenase (2 degrees Adh) as a bifunctional alcohol dehydrogenase--acetyl-CoA reductive thioesterase. , 1994, The Biochemical journal.

[5]  R. Csuk,et al.  Baker's yeast mediated transformations in organic chemistry , 1991 .

[6]  R. Phillips,et al.  Effects of substrate structure and temperature on the stereospecificity of secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus , 1990 .

[7]  K. Faber,et al.  Strategies for the chemoenzymatic preparation of optically active 1-alkyn-3-ols. , 1990, Chemistry and physics of lipids.

[8]  E. Keinan,et al.  Thermostable enzymes in organic synthesis. 2. Asymmetric reduction of ketones with alcohol dehydrogenase from Thermoanaerobium brockii , 1986 .

[9]  K. Vollhardt,et al.  The preparation of 2(1H)-pyridinones and 2,3-dihydro-5(1H)-indolizinones via transition metal mediated cocyclization of alkynes and isocyanates. A novel construction of the antitumor agent camptothecin , 1984 .

[10]  D. Walton,et al.  Friedel-crafts reactions of bis(trimethylsilyl)polyynes with acyl chlorides; a useful route to terminal-alkynyl ketones , 1972 .