cis-5-vinyl-L-proline | 138957-95-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: cis-5-vinyl-L-proline
• 英文别名: cis-5-Vinylproline；(2S,5R)-5-ethenylpyrrolidine-2-carboxylic acid
• CAS: 138957-95-6
• 化学式: C₇H₁₁NO₂
• 分子量: 141.17
• InChiKey: LHZVEMUCVVXLGQ-WDSKDSINSA-N

物化性质

• 沸点：
  261.3±40.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-carbomethoxy-5-methoxy-L-proline methyl ester 在 Lindlar's catalyst sodium hydroxide 、 三甲基氯硅烷 、 四丁基氟化铵 、 氢气 、 四氯化钛 、 sodium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 15.17h， 生成 cis-5-vinyl-L-proline
  参考文献：
  名称：

  Syntheses of proline analogs as potential mechanism-based inhibitors of proline dehydrogenase: 4-methylene-L-, (E)- and (Z)-4-(fluoromethylene)-L-, cis- and trans-5-ethynyl-(.+-.)-, and cis- and trans-5-vinyl-L-proline

  摘要：

  Proline dehydrogenase is an enzyme involved in the energetic processes required for flight in certain insects including the tse-tse fly. Proline analogues were designed for the inhibition of this enzyme. For this purpose 4-methylene-L-proline and (E)- and (Z)-4-(fluoromethylene)-L-proline were prepared from trans-4-hydroxyl-L-proline through the following sequence: protection at the nitrogen with a tert-butoxycarbonyl and at the caboxylic acid as methyl ester, oxidation of the hydroxyl group to a ketone, Wittig reaction, and removal of the protecting groups. The cis- and trans-5-ethynyl-(+/-)-proline was prepared from N-(tert-butoxycarbonyl)-3-(trimethylsilyl)-2-propynylamine whose dianion reacted with 1,2-epoxy 4-bromobutane. Cyclization in the presence of trifluoroacetic acid, oxidation of the primary alcohol to acid, and removal of the protecting groups gave cis- and trans-5-ethynyl-(+/-)-proline. Stereoselectivity was observed in the reaction of the dianion of 3-(trimethylsilyl)-2-propynylamine with 1,2-epoxy-4-bromobutane. The cis- and trans-5-vinyl-L-prolines were prepared from N-(methoxycarbonyl)-5-methoxy-L-proline ester by reaction with bis(trimethylsilyl)acetylene in the presence of titanium tetrachloride followed by sequential removal of the protecting groups and by reduction. The cis and trans configuration of the 5-vinyl-L-proline obtained was established by comparison of the NMR spectrum of the trans-N-tosyl-5-vinyl-(+/-)-proline methyl ester with the published spectrum of the trans derivative.

  DOI：

  10.1021/jo00033a029

文献信息

• [EN] MASP INHIBITORY COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS INHIBITEURS DE MASP ET LEURS UTILISATIONS
  申请人：BAYER AG

  公开号：WO2020225095A1

  公开（公告）日：2020-11-12

  The present invention relates to novel Mannose-binding lectin (MBL)-associated serine protease (MASP) inhibitory compounds, as well as analogues and derivatives thereof, to processes for the preparation thereof, to the use thereof alone or in combinations for treatment and/or prevention of diseases and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially for treatment and/or prevention of renal and cardiovascular disorders and of ischemia reperfusion injuries.

  本发明涉及新型甘霖结合凝集素（MBL）相关丝氨酸蛋白酶（MASP）抑制化合物，以及其类似物和衍生物，以及其制备方法，单独或组合用于治疗和/或预防疾病，以及用于生产药物治疗和/或预防疾病，特别是用于治疗和/或预防肾脏和心血管疾病以及缺血再灌注损伤。
• INHIBITION OF PROLINE CATABOLISM FOR THE TREATMENT OF CANCER AND OTHER THERAPEUTIC APPLICATIONS
  申请人：Buck Institute for Research on Aging

  公开号：US20170348266A1

  公开（公告）日：2017-12-07

  In various embodiments a cancer treatment method is provided based on inhibition of proline catabolism. When combined with p53 restoration therapy and/or inhibition of glutaminase, the inhibition of proline catabolism results in a “synthetic lethal” and synergistic anticancer response. Novel suicide inhibitors that induce the degradation of proline dehydrogenase (PRODH) are also provided. Also provided is a method of assaying PRODH to identify responders/non-responders to inhibition of proline catabolism and/or glutaminase.
• MASP INHIBITORY COMPOUNDS AND USES THEREOF
  申请人：Bayer Aktiengesellschaft

  公开号：US20210246166A1

  公开（公告）日：2021-08-12

  The present invention relates to novel Mannose-binding lectin (MBL)-associated serine protease (MASP) inhibitory compounds, as well as analogues and derivatives thereof, to processes for the preparation thereof, to the use thereof alone or in combinations for treatment and/or prevention of diseases and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially for treatment and/or prevention of renal and cardiovascular disorders and of ischemia reperfusion injuries.
• [EN] INHIBITION OF PROLINE CATABOLISM FOR THE TREATMENT OF CANCER AND OTHER THERAPEUTIC APPLICATIONS<br/>[FR] INHIBITION DU CATABOLISME DE LA PROLINE POUR LE TRAITEMENT DU CANCER ET D'AUTRES APPLICATIONS THÉRAPEUTIQUES
  申请人：BUCK INST FOR RES ON AGING

  公开号：WO2016077632A2

  公开（公告）日：2016-05-19

  In various embodiments a cancer treatment method is provided based on inhibition of proline catabolism. When combined with p53 restoration therapy and/or inhibition of glutaminase, the inhibition of proline catabolism results in a "synthetic lethal" and synergistic anticancer response. Novel suicide inhibitors that induce the degradation of proline dehydrogenase (PRODH) are also provided. Also provided is a method of assaying PRODH to identify responders/non-responders to inhibition of proline catabolism and/or glutaminase.
• Syntheses of proline analogs as potential mechanism-based inhibitors of proline dehydrogenase: 4-methylene-L-, (E)- and (Z)-4-(fluoromethylene)-L-, cis- and trans-5-ethynyl-(.+-.)-, and cis- and trans-5-vinyl-L-proline
  作者：Franco Manfre、Jean Marc Kern、Jean Francois Biellmann

  DOI：10.1021/jo00033a029

  日期：1992.3

  Proline dehydrogenase is an enzyme involved in the energetic processes required for flight in certain insects including the tse-tse fly. Proline analogues were designed for the inhibition of this enzyme. For this purpose 4-methylene-L-proline and (E)- and (Z)-4-(fluoromethylene)-L-proline were prepared from trans-4-hydroxyl-L-proline through the following sequence: protection at the nitrogen with a tert-butoxycarbonyl and at the caboxylic acid as methyl ester, oxidation of the hydroxyl group to a ketone, Wittig reaction, and removal of the protecting groups. The cis- and trans-5-ethynyl-(+/-)-proline was prepared from N-(tert-butoxycarbonyl)-3-(trimethylsilyl)-2-propynylamine whose dianion reacted with 1,2-epoxy 4-bromobutane. Cyclization in the presence of trifluoroacetic acid, oxidation of the primary alcohol to acid, and removal of the protecting groups gave cis- and trans-5-ethynyl-(+/-)-proline. Stereoselectivity was observed in the reaction of the dianion of 3-(trimethylsilyl)-2-propynylamine with 1,2-epoxy-4-bromobutane. The cis- and trans-5-vinyl-L-prolines were prepared from N-(methoxycarbonyl)-5-methoxy-L-proline ester by reaction with bis(trimethylsilyl)acetylene in the presence of titanium tetrachloride followed by sequential removal of the protecting groups and by reduction. The cis and trans configuration of the 5-vinyl-L-proline obtained was established by comparison of the NMR spectrum of the trans-N-tosyl-5-vinyl-(+/-)-proline methyl ester with the published spectrum of the trans derivative.