Chemical and Biochemical Studies on a New Alcohol Dehydrogenase

新型乙醇脱氢酶的化学和生化研究

• 批准号: 10490025
• 负责人: OHTA Hiromichi
• 金额: $ 3.46万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10490025/
• 关键词: Yamadazyma farinosa; microbial reduction; asymmetric reduciton; optically active alcohols; trifluoromethylketone; optically active styrene glycol; dihydroxyacetone; スルフィニルケトン; 生体触媒; ケトアルデヒド

Asymmetric reduction of caronyl compounds utilizing a yeast, Yamadazyma farinosa IFO 10896, has been developed. It was revealed that this yeast has the ability to reduce not only methyl ketones but also trifluoromethyl ketones in a highly enantioselective manner. The spacial arrangement of the ligands around the asymmetric carbon of the resulting alcohols are the same with each other. The sulfur functionalities on the other side of the carbonyl group are effective topromote the reaction and its stereochemical selectivity. It is worth noting that the configuration of the sulfoxide moiety on the α position of the carbonyl have serious effect on the enantioselectivity of the reaction, in which (S)-sulfoxide gave the higher selectivity.Methyl ketones with an acetal functionality are also good substrates to this biocatalyst. The optically active hydroxy aldehyde can be derived to optically active diols by the following derivations utilizing organometallic reagents.α-Hydroxy ketones were also subjected to the mycrobial reductions. For example, α- hydroxyacetophenone was smoothly reduced to (S)-styrene glycol. As the hydrooxymethyl group and phenyl ring can be separately oxidized to aldehyde functionality, the carbon-chain elongation is possible to both sides of the resulting chiral center. Mono-protected dihydroxyacetones were also reduced by this yeast. However, the selectivity and reactivity are desirable to be more improved.

利用酵母菌Yamadazyma farinosa IFO 10896不对称还原羧基化合物已被开发出来。结果表明，该酵母不仅具有还原甲基酮的能力，而且对三氟甲基酮具有高度的对映选择性。生成的醇的不对称碳周围的配体的空间排列是彼此相同的。羰基另一侧的硫官能团有效地促进了反应及其立体化学选择性。值得注意的是，羰基α位上亚砜的构型对反应的对映选择性有很大影响，其中(S)亚砜具有较高的选择性，具有缩醛官能团的甲基酮也是该生物催化剂的良好底物。光学活性的羟基醛可以通过下列利用有机金属试剂的衍生物得到光学活性的二元醇。α-羟基酮也经历了霉菌的还原。例如，α-羟基苯乙酮被顺利还原为(S)-苯乙烯乙二醇。由于羟甲基和苯环可以被分别氧化成醛的官能团，所以碳链可以延伸到得到的手性中心的两侧。该酵母还能还原单基保护的二羟基丙酮。但选择性和反应活性有待进一步提高。

项目成果

Atsushi Sakai: "Synthesis of (Rc,Ss)-1,1,1-Trifluoro-3-(p-tolylsulifinyl)-2-propanol by an Asymmetric Reduction with a Yeast,Yamadazyma farinosa,as a Key-step"Chemistry Letters. 1255-1256 (1999)

Atsushi Sakai：“通过酵母山田酵母粉的不对称还原合成 (Rc,Ss)-1,1,1-三氟-3-(对甲苯磺酰基)-2-丙醇作为关键步骤”化学快报

Sakai,A.: "Synthesis of (Rc,Ss)-1,1,1-Trifluoro-3-(p-tolysulfinyl)-2-propanol by an Asymmetric Reduction with a Yeast, Yamadazyma farinosa, as a Key-step"Chem.Lett.. 1255-1256 (1999)

Sakai,A.：“通过酵母 Yamadazyma farinosa 的不对称还原合成 (Rc,Ss)-1,1,1-三氟-3-(对甲苯磺酰基)-2-丙醇作为关键步骤”

Yamazaki,T: "Yamadazyma farinosa IFO 10896-Mediated Reduction of 4,4-Dimethoxy-2-butanone as the Key-Step for the Preparation of 1,3-Diols with Unsymmetrical Substituents."Synth.Commun.. 30. 3061-3072 (2000)

Yamazaki,T：“Yamadazyma farinosa IFO 10896-介导的 4,4-二甲氧基-2-丁酮还原是制备具有不对称取代基的 1,3-二醇的关键步骤。”Synth.Commun.. 30. 3061-

Sakai, A., Bakke, M., Ohta, H., Kosugi, H., Sugai, T.: "Synthesis of (Rc, Ss)-1, 1, 1-Trifluoro-3-(p-tolylsulfinyl)-2-propanol by an Asymmetric Reduction with a Yeast, Yamadazyama farinosa, as a Key-step"Chem.Lett.. 1255-1256 (1999)

Sakai, A.、Bakke, M.、Ohta, H.、Kosugi, H.、Sugai, T.：“(Rc, Ss)-1, 1, 1-三氟-3-(对甲苯基亚磺酰基)-的合成

Yamazaki, T., Kuboki, A., Ohta, H., Mitzel, T.M., Paquett, L.A., Sugai, T.: "Yamadazyma farinosa IFO 10896-Mediated Reduction of 4, 4-Dimethoxy-2-butanone as the Key-Step for the Preparation of 1, 3-Diols with Unsymmetrical Substituents."Synth.Commun.. 30

Yamazaki, T.、Kuboki, A.、Ohta, H.、Mitzel, T.M.、Paquett, L.A.、Sugai, T.：“Yamadazyma farinosa IFO 10896-介导的 4, 4-二甲氧基-2-丁酮还原作为关键-