Development of Microbial Enzymatic Catalysts towards the Chemo-Enzymatic Synthesis of Bioactive Substances

微生物酶催化剂的开发用于生物活性物质的化学酶合成

• 批准号: 14560084
• 负责人: SUGAI Takeshi
• 金额: $ 2.3万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14560084/
• 关键词: Microbial Enzymes; Yeast-mediated Reduction; Natural Product Synthesis; Kinetic Resolution; Amino Acid; 加水分解酵素

An important aspect in the enzyme-catalyzed production of chemicals is the complementary and synergistic use of chemo-enzymatic procedure so that we can draw a reasonable and straightforward blueprint towards the target molecules. Needless to say, a remarkable advantage is that enzymes are the catalysts whose supply from microorganisms, animals, and plants never quit, as the resources can be reproduced in a self-production manner.In this study supported by the grant-in-aid (2002-2003), the achievements were ; 1) lipase-mediated kinetic resolution of heterocyclic amino acids including N-protected forms of proline and N-protected forms of indolinecarboxyolic acid ; 2) Asymmetrization of prochira diketones by means of a yeast (Torulaspora delbrueckii) catalyzed reduction to provide enantiomerically pure cyclic hemiacetals ; 3) Radical-mediated conversion of the cyclic acetals to α-alkenyl-substituted β-hydroxycyclohexanone, which would be the starting material of terpenoids such as tryptocallols and madindolines ; 4) substrate specificity study and long-term preservable cell preparation of the above new biocatalyt, Torulaspora delbrueckii ; 5) combination of electroorganic chemistry (constant current electrolysis) and enzyme-catalyzed desymmetrization of a prochiral diester to give the key intermediate of natural occurring bioactive product, such as helianulol E.

酶催化生产化学品的一个重要方面是化学-酶过程的互补和协同使用，以便我们可以绘制合理和直接的目标分子蓝图。不用说，酶是催化剂，微生物、动物和植物的供应永远不会停止，因为这些资源可以以自我生产的方式再生。（2002-2003年），取得的成绩是：1）脂肪酶介导的包括N-保护形式的脯氨酸和N-保护形式的二氢吲哚羧酸的杂环氨基酸的动力学拆分; 2）通过酵母不对称化原手性二酮（Torulasporadelbrueckii）催化还原得到对映体纯的环状半缩醛; 3）自由基介导的环状缩醛转化为α-烯基取代的β-羟基环己酮，其将是萜类化合物如色卡洛尔和madindolines的起始原料; 4）上述新型生物催化剂德氏圆孢酵母的底物特异性研究和长期可保存细胞制备; 5）将有机电化学（恒流电解）和酶催化的前手性二酯去对称化相结合，得到天然生物活性产物的关键中间体，例如helianulol E。

项目成果

K.Fuhshuku, M.Tomita, T.Sugai: "Unprecedented Chemo-enzymatic Synthesis of Stereochemically Pure 3-Acetoxy-2-methyl-2-vinylcycloalkanones"Tetrahedron Lett.. 45. 1763-1767 (2004)

K.Fuhshuku、M.Tomita、T.Sugai：“前所未有的立体化学纯 3-乙酰氧基-2-甲基-2-乙烯基环烷酮的化学酶合成”Tetrahedron Lett.. 45. 1763-1767 (2004)

F.Doi, T.Ogamino, T.Sugai, S.Nishiyama: "Enantioselective Synthesis of Helianulol E ; Structural Consideration of Natural Molecule"Tetrahedron Lett.. 44. 4877-4880 (2003)

F.Doi、T.Ogamino、T.Sugai、S.Nishiyama：“Helianulol E 的对映选择性合成；天然分子的结构考虑”Tetrahedron Lett.. 44. 4877-4880 (2003)

M.Kimura, A.Kuboki, T.Sugai: "Chemo-enzymatic Synthesis of Enantiomerically Pure (R)-2-Naphthyl-methoxyacetic acid"Tetrahedron : Asymmetry. 13. 1059-1068 (2002)

M.Kimura、A.Kuboki、T.Sugai：“对映体纯 (R)-2-萘基-甲氧基乙酸的化学酶合成”四面体：不对称性。

K.Fuhshuku, T.Sugai: "Access to Enantiomerically Pure Intermediates of Geosmin Synthesis Starting from (4aS,8S)-4,4a,5,6,7,8-Hexahydro-4a,8-dimethylnaphthalen-2(3H)-one"Biosci.Biotechnol.Biochem.. 66. 2267-2272 (2002)

K.Fuhshuku, T.Sugai：“从 (4aS,8S)-4,4a,5,6,7,8-六氢-4a,8-二甲基萘-2(3H)-开始合成土臭素的对映体纯中间体

M.Kurokawa, T.Shindo, M.Suzuki, N.Nakajima, K.Ishihara, T.Sugai: "Enzyme-catalyzed Enantiomeric Resolution of N-Boc-proline as the Key-step in an Expeditious Route toward RAMP"Tetrahedron : Asymmetry. 14. 1323-1333 (2003)

M.Kurokawa、T.Shindo、M.Suzuki、N.Nakajima、K.Ishihara、T.Sugai：“酶催化 N-Boc-脯氨酸的对映体拆分是迈向 RAMP 四面体快速路线的关键步骤”：