Regio- and Stereoselective Reduction of Substituted 1.3-Dicarbonyl Compounds by Use of Bakers' Yeast

使用面包酵母对取代的 1.3-二羰基化合物进行区域选择性和立体选择性还原

• 批准号: 04650775
• 负责人: UTAKA Masanori
• 金额: $ 1.22万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04650775/
• 关键词: optically active gamma -substituted beta -hydroxy ketones; Bakers' yeast asymmetric reduction; trifunctional chiral synthons; optically active alpha -acetoxy alcohols; optically active chlorohydrins; 光学活性1,2-ジオール誘導体; 1,3-ジケトン; α-アセトキシケトン; 1-アセトキシ-

1. Effects of Additives of the Bakers' Yeast Reduction of 1-Chloro-2,4-alkanediones---The % ee values of reduction products were found to be enhanced by addition of SrCl_2 in 2 mol/L to the aqueous reaction solution. Other metal chlorides also exhibited similar effects, though not so large. The effects can be attributed to selective activation or inhibition of additives toward plural reducing enzymes.2. Bakers' Yeast Reduction of 1-Acetoxy-2,4-alkanediones ---The reduction produced (S)-1-acetoxy-2-hydroxy-4-alkanones in 40 - 90% ee, as compared with the reduction of 1-acetoxy-2-alkanones with 95 - >99% ee. The somewhat diminished % ee values can be attributed to the presence of an oxo functional group at C-4. The oxo group effectively suppressed the hydrolysis of the acetoxy group, which occurred for 1-acetoxy-2-alkanones and produces 1,2-diols as by-product. The optically active trifunctional products are useful as chiral synthons.3. Highly Efficient Asymmetric Reduction by Use of Bakers' Yeast Cell-Free Extract---The cell-free extract was found to reduce 1-acetoxy-2-alkanones to 1-acetoxy-2-alkanols in 59 - 88% yield and 95 - >99% ee by use of a catalytic amount of NADPH with glucose as hydride source and without addition of any enzyme for the cofactor regeneration. This method is expected to be applicable to 1-chloro- and 1-acetoxy-2,4-alkanediones.

1.酵母添加剂对1-氯-2，4-烷二酮还原反应的影响--在反应液中加入2 mol/L的SrCl_2可提高还原产物的ee值。其他金属氯化物也表现出类似的效果，尽管没有那么大。这种效应可能是由于添加剂对多种还原酶的选择性激活或抑制. 1-乙酰氧基-2，4-烷二酮的面包酵母还原--还原产生的（S）-1-乙酰氧基-2-羟基-4-烷酮的ee值为40 - 90%，而1-乙酰氧基-2-烷酮的ee值为95 - >99%。氧代基团有效地抑制了1-乙酰氧基-2-烷酮发生的乙酰氧基水解，并产生作为副产物的1，2-二醇。光学活性的三官能产物可用作手性配体。利用面包酵母无细胞提取物的高效不对称还原-发现无细胞提取物以59 - 88%的产率和95 - > 99%ee将1-乙酰氧基-2-烷酮还原为1-乙酰氧基-2-烷醇，通过使用催化量的NADPH，以葡萄糖作为氢化物源，并且不添加任何用于辅因子再生的酶。该方法可望适用于1-氯-和1-乙酰氧基-2，4-烷二酮。

项目成果

Kohji Ishihara,Nobuyoshi Nakajima,Sadao Tsuboi,Masanori Utaka: "Purification and Characterization of α-Acetoxy Ketone Reductase from Bakers' Yeast(Saccharomyces cerevisiae)" Journal of Biochemistry. (to be published). (1994)

Kohji Ishihara、Nobuyoshi Nakajima、Sadao Tsuboi、Masanori Utaka：“来自面包酵母（酿酒酵母）的 α-乙酰氧基酮还原酶的纯化和表征”《生物化学杂志》（1994 年）。

Masanori Utaka,Toshiyuki Mizumoto,Sadao Tsuboi: "Regio- and Enantioselective Reduction of 1-Acetoxy-2,4-alkanediones by Use of Fermenting Bakers' Yeast" Tetrahedron Letters. 35(to be published). (1994)

Masanori Utaka、Toshiyuki Mizumoto、Sadao Tsuboi：“利用发酵面包酵母对 1-乙酰氧基-2,4-烷二酮进行区域和对映选择性还原”四面体字母。

Kohji Ishihara, Nobuyoshi Nakajima, Sadao Tsuboi, Masanori Utaka: "Purification and Characterization of alpha -Acetoxy Ketone Reductase from Bakers' Yeast (Saccharomyces cerevisiae)" Journal of Biochemistry. (to be published). (1994)

Kohji Ishihara、Nobuyoshi Nakajima、Sadao Tsuboi、Masanori Utaka：“面包酵母（酿酒酵母）中 α-乙酰氧基酮还原酶的纯化和表征”生物化学杂志。

Kohji Ishihara: "Highly Efficient Enzymatic Asymmetric Reduction by Use of Regenerating NADPH in Bakers' Yeast Cell-Free---" Tetrahedron Letters. 35. (1994)

Kohji Ishihara：“通过在无细胞面包酵母中使用再生 NADPH 进行高效酶促不对称还原——”四面体信件。

Kohji Ishihara,Takashi Sakai,Masanori Utaka: "Highly Efficient Enzymatic Asymmetric Reduction by Use of Regenerating NADPH in Bakers' Yeast Cell-Free Extract" Tetrahedron Letters. 35. (1994)

Kohji Ishihara、Takashi Sakai、Masanori Utaka：“在面包酵母无细胞提取物中使用再生 NADPH 进行高效酶促不对称还原”四面体字母。