Origination of functional chiral building blocks using asymmetric acylation and application to the synthesis of biologically active compounds

利用不对称酰化衍生功能性手性构件及其在生物活性化合物合成中的应用

• 批准号: 05671743
• 负责人: TAKAHATA Hiroki
• 金额: $ 1.22万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL 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: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671743/
• 关键词: Asymmetric acylation; Lipase; Chiral building block; Chiral synthesis; gamma-Butyrolactone; Intramolecular lactonization; Stereoselective synthesis; Insect pheromone; ヨードラクトン化; オキシラクトン化

Enzymes are now recognized as substrate-specific and highly enantioselective catalyst for asymmetric synthesis. In particular, lipases have recently been used for biocatalytic resolutions on the basis of the admission of organic solvents as reaction media.We succeeded immobilized lipase-mediated resolution of N,N-dialky1-3-hydroxy-4-pentenamides, unsuccessful in resolution by the Katsuki-Sharpless asymmetric epoxidation. Iodolactonizaion of thus prepared homochiral amides and oxy-lactonization of O-protected homochiral amides proceeded stereoselectively, affording both enantiomers of cis-3,4-disubstituted gamma-lactone and both enantiomers of trans-3,4, disubstituted gamma-lactone preferentially, respectively.These gamma-lactones have been used as chiral building blocks for the synthesis of biological active compounds such as litsenolides, (+) -blastimycinone, NFX-2, NFX-4, metabolites from Gorgonian Plexaura flava, and muscarine.Especially, cis-3,4-disubstituted gamma-lactones were served as the masked butenolide chirons and a concise synthesis of (+) -trans-wisky and (+) -trans-cognac lactones, (-) -methylenolactocin, (+) -nephrosteranic acid, and (+) -roccellaric acid has been achieved.In addition, these gamma-lactones have been apllied as chiral carbon five building blocks for the synthesis of insect pheromons.

酶是一类具有底物专一性和高对映选择性的不对称合成催化剂。特别是近年来，脂肪酶在有机溶剂作为反应介质的基础上被应用于生物催化拆分，我们成功地将Katsuki-Sharpless不对称环氧化法拆分不成功的N，N-二烷基-3-羟基-4-戊烯酰胺类化合物固定化在脂肪酶的催化下进行拆分。对所合成的纯手性酰胺进行碘内酯化和O-保护的纯手性酰胺进行氧内酯化反应，分别优先得到顺式-3，4-二取代γ-内酯和反式-3，4-二取代γ-内酯，这些γ-内酯已被用作合成生物活性化合物如木脂素内酯、（+）-blastimycinone、本文以柳珊瑚Plexaura flava的代谢产物NFX-2、NFX-4和muscarine为原料，以cis-3，4-二取代γ-内酯为掩蔽的丁烯酰手性化合物，合成了（+）-trans-wisky和（+）-trans-cognac内酯、（-）-亚甲基乳糖苷、（+）-肾甾烷酸和（+）-roccellaric酸。这些γ-内酯已被用作合成昆虫信息素的手性碳五结构单元。

项目成果

高畑広紀: "Enzymatic lesolution of N_1N-dialkyl-3-hydroxy-4-pentenamide,unsnccessful in resolution by the Katsuki-Sharpless asymmetric epoxidation" Tetrahedron:Asymmetry. 4. 1041-1042 (1993)

Hironori Takahata：“N_1N-二烷基-3-羟基-4-戊烯酰胺的酶解，通过 Katsuki-Sharpless 不对称环氧化拆分失败”四面体：不对称。 4. 1041-1042 (1993)

Journal of Organic Chemistry. 59. 7201-7208 (1994)

有机化学杂志。

Takahata, Hiroki: "Enzymic resolution of N,N-dialky1-3-hydroxy-4-pentenamides, unsuccessful in resolution by the Katsuki-Sharpless asymmetric epoxidation" Tetrahedron : Asymmetry. 4. 1041-1042 (1993)

Takahata，Hiroki：“N,N-二烷基 1-3-羟基-4-戊烯酰胺的酶拆分，通过 Katsuki-Sharpless 不对称环氧化拆分失败”四面体：不对称性。

高畑広紀: "New entry to Chirul butenolide synthons.Application to expeditious syntheses of (+) nephrosterunic acid,(+)-trans-whisky lactone,and (+)-trans-cognac lactone" Tetrahedron Letters. 35. 4123-4124 (1994)

Hironori Takahata：“Chirul 丁烯酸内酯合成子的新条目。在 (+) 肾胸烯酸、(+)-反式威士忌内酯和 (+)-反式白兰地内酯的快速合成中的应用”四面体快报 35。4123-4124（ 1994）

Takahata, Hiroki: "Highly selective intramoleccular heterocyclization and its application to synthesis of biologically active compounds" Yakugaku Zasshi. 113. 737-759 (1993)

Takahata、Hiroki：“高选择性分子内杂环化及其在生物活性化合物合成中的应用”Yakugaku Zasshi。