Synthesis of Phamacologically Active Compounds using Asymmetric Radical Cyclization

使用不对称自由基环化合成药理活性化合物

• 批准号: 07672300
• 负责人: IKEDA Masazumi
• 金额: $ 1.41万
• 依托单位: Kyoto Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672300/
• 关键词: radical cyclization; asymmetric synthesis; asymmetric radical cylization; beta-lactam; (+) -thienamycin; (-) -1beta-methycarbapenem; chiral auxiliary; キラル補助剤; octahydroindol-2-one; (+)-チェナマイシン; (-)-1 β-メチルカルバペネム

Asymmetric induction in radical cyclization of N-vinylic alpha-halo amides was investigated.1, Radical cyclization of 2-bromo-N- [2- (m-methoxyphenyl) -2- phenylthio-1-ethenyl] butanamide dearing (S) -1-phenylethyl group on the nitrogen atom as a chiral auxiliary group gave the (3R,4R) -2-azetidinone as the major product, which was transformed into the intermediate for the synthesis of (+) -PS-5.2, Radical cyclization of (2R,3S) -3-acetoxy-2-bromo-N- [2- (m-methoxyphenyl) -2-phenylthio-1-ethenyl] butanamide gave the (3S,4R) -2-azetidinone as the major product, which was transformed into the intermediate for the synthesis of (+) -thienamycin.3, Radical cyclization of (2R,3S) -3-acetoxy-2-bromo-N- [2- (m-methoxyphenyl) -1-propenyl] butanamide gave the (3S,4R) -2-azetidinone as the major product, which was transformed into the intermediate for the synthesis of (-) -1beta-methylcarbapenem.4, Radical cyclization of N- (cyclohexen-1-yl) -N-methyl-alpha-haloacetamide bearting (S) -1- (1-naphethyl) ethyl group on the nitrogen atom gave the (3aR,7aR) -octahydroindol-2-one as the major product.

研究了N-乙烯基α-卤代酰胺自由基环化反应中的不对称诱导反应. 1、2-溴-N- [2-（2-甲氧基苯基）-2-甲基]-N-（2-甲氧基苯基）-N-（2-甲氧基（间甲氧苯基）-2-苯硫基-1-乙烯基]丁酰胺脱氮原子上的（S）-1-苯乙基作为手性辅助基团，得到（3R，4 R）-2-氮杂环丁酮作为主要产物，（2 R，3S）-3-乙酰氧基-2-溴-N- [2-（2-甲氧基苯基）-3-甲基-N-（2-甲氧基苯基）-N-甲基-N-（2-甲氧基苯基）-N-甲基-N-（2-甲氧基苯基）（2 R，4 R）-2-氮杂环丁酮经自由基环化，3S）-3-乙酰氧基-2-溴-N- [2-（2-甲基-IH-吡唑-4-基）-3-甲基-IH-吡唑-4-基]-苯并[d]咪唑（间甲氧苯基）-1-丙烯基]丁酰胺得到（3S，4 R）-2-氮杂环丁酮作为主要产物，其被转化为合成（-）-1 β-甲基碳青霉烯的中间体。N-自由基环化在氮原子上带有（S）-1-（1-萘基）乙基的（环己烯-1-基）-N-甲基-α-卤代乙酰胺得到作为主要产物的（3aR，7aR）-八氢吲哚-2-酮。

项目成果

石橋 弘行: "Asymmetric radical cyclization leading to β-lactams : Stereoselective synthesis of a chiral key intermeditates for carbapenem antibiotics PS-5" Tetrahedron. 52(2). 489-502 (1996)

Hiroyuki Ishibashi：“导致 β-内酰胺的不对称自由基环化：碳青霉烯类抗生素 PS-5 的手性关键中间体的立体选择性合成”Tetrahedron 52(2) (1996)。

石橋 弘行: "Sulfur-directed regioselective radical cyclization leading to β-lactams : Formal synthesis of (【.+-。】)-PS-5 and (+)-thienamycin" J.Org.Chem.60(5). 1276-1284 (1995)

Hiroyuki Ishibashi：“硫引导的区域选择性自由基环化导致β-内酰胺：(【.+-．】)-PS-5 和(+)-硫霉素的正式合成”J.Org.Chem.60(5)。 -1284 (1995)

Hiroyuki Ishibashi, Chisato Kameoka, Kazuya Kodama, and Masazumi Ikeda : Asymmetric radical cyclization leading to beta-1actams: "Stereoselective synthesis of chiral key intermeditates for carbapenem antibiotics PS-5." Tetrahedron. 52-2. 489-502 (1996)

Hiroyuki Ishibashi、Chisato Kameoka、Kazuya Kodama 和 Masazumi Ikeda：产生 β-1 内酰胺的不对称自由基环化：“碳青霉烯类抗生素 PS-5 手性关键中间体的立体选择性合成”。

石橋 弘行: "Synthesis of 4-oxo-2-azetidineacetic acids by means of radical cyclization of N-vinylic α-bromo amides" Tetrahedron : Asymmetry.7(44). 2531-2538 (1996)

Hiroyuki Ishibashi：“通过 N-乙烯基 α-溴酰胺的自由基环化合成 4-氧代-2-氮杂环丁烷乙酸”Tetrahedron：Asymmetry.7(44) (1996)。

石橋弘行: "Radical cyclization of chiral N-(1-cycloalken-1-yl)-α-haloacetamides : Synthesis of optically active bicyclic pyrrolidinones" Tetrahedron. 52(44). 13867-13880 (1996)

Hiroyuki Ishibashi：“手性 N-(1-环烯-1-基)-α-卤代乙酰胺的自由基环化：光学活性双环吡咯烷酮的合成”Tetrahedron 52(44)。