N-tert-butoxycarbonyl-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-talitol | 1022094-08-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: N-tert-butoxycarbonyl-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-talitol
• 英文别名: tert-butyl (3aS,4S,6aR)-4-[(S)-1,2-dihydroxyethyl]-2,2-dimethyltetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate；tert-butyl (3aS,4S,6aR)-4-[(1S)-1,2-dihydroxyethyl]-2,2-dimethyl-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
• CAS: 1022094-08-1
• 化学式: C₁₄H₂₅NO₆
• 分子量: 303.356
• InChiKey: XYSIRGYTUNWJCJ-CHWFTXMASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-tert-butoxycarbonyl-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-talitol 在 sodium periodate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以100%的产率得到(2R,3S,4R)-N-tert-butoxycarbonyl-2-formyl-3,4-O-isopropylidenepyrrolidine-3,4-diol
  参考文献：
  名称：

  Tuning of β-glucosidase and α-galactosidase inhibition by generation and in situ screening of a library of pyrrolidine-triazole hybrid molecules

  摘要：

  The preliminary screening of two libraries of epimeric (pyrrolidin-2-yl)triazoles (14a-s and 22a-s), generated via click chemistry, allowed the rapid identification of four alpha-galactosidase (coffee beans) inhibitors (22b,k,p,r) and two beta-glucosidase (almond) inhibitors (14b,f) in the low mu M range. The additional biological analysis of 14b,f towards beta-glucocerebrosidase (human lysosomal beta-glucosidase), as target enzyme for Gaucher disease, showed a good correlation with the inhibition results obtained for the plant (almond) enzyme. Surprisingly, although these compounds showed inhibition towards beta-glucocerebrosidase as acid hydrolase, they did not inhibit bovine liver beta-glucosidase as neutral hydrolase. In contrast to what was observed for beta-glucosidase inhibition, the coffee bean alpha-galactosidase inhibitors of the epimeric library (22b,k,p,r) only showed weak inhibition towards human lysosomal alpha-galactosidase. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.06.055
• 作为产物：
  描述：

  2,3,5,6-di-isopropyIidene-1,4-dihydroxy-D-mannitol 在 吡啶 、 palladium on activated charcoal 、 氢气 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 51.83h， 生成 N-tert-butoxycarbonyl-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-talitol
  参考文献：
  名称：

  靶向锌依赖性脱乙酰基酶LpxC的基于脯氨酸的异羟肟酸酯：合成，抗菌性能和对接研究。

  摘要：

  依赖Zn2 +的脱乙酰基酶LpxC是革兰氏阴性细菌中必不可少的酶，已被确认为抗菌药物的靶标。本文中，我们报道了新颖的d和l-脯氨酸衍生的3,4-二羟基吡咯烷异羟肟酸酯的手性池合成，并将它们的抗菌和LpxC抑制活性与4-单取代和3,4-未取代的脯氨酸衍生物进行了比较。具有对几种革兰氏阴性病原体的有效抗菌活性，基于脯氨酸的叔胺41g（（S）-N-羟基-1-（4-{[4-（吗啉代甲基）苯基]乙炔基}苄基）吡咯烷-2 （羧酰胺）被发现是所研究系列中最具活性的抗菌化合物，对几种人类MMP表现出对EcLpxC（Ki = 1.4μM）的选择性。

  DOI：

  10.1016/j.bmc.2019.03.056

文献信息

• Pyrrolidine‐Based P,O Ligands from Carbohydrates: Easily Accessible and Modular Ligands for the Ir‐Catalyzed Asymmetric Hydrogenation of Minimally Functionalized Olefins
  作者：Pilar Elías‐Rodríguez、Carlota Borràs、Ana T. Carmona、Jorge Faiges、Inmaculada Robina、Oscar Pàmies、Montserrat Diéguez

  DOI：10.1002/cctc.201801485

  日期：2018.12.7

  The potential of P,O‐iminosugar based ligands in the Ir‐catalyzed asymmetric hydrogenation of minimally functionalized olefins is presented. These new ligands were prepared from easily available carbohydrates (D‐mannose, D‐ribose and D‐arabinose). The stereochemical and polyfunctional diversity of carbohydrates allowed the modulation of the ligands, both from their electronic properties and the rigidity

  提出了基于P，O-亚氨基糖的配体在Ir催化的最小官能化烯烃的不对称加氢中的潜力。这些新的配体由容易获得的碳水化合物（D-甘露糖，D-核糖和D-阿拉伯糖）制备。碳水化合物的立体化学和多官能度多样性可从其电子特性和主链刚性两个方面对配体进行调节。在选定的三取代和二取代的底物进行氢化反应时，可以达到较高的对映选择性（ee高达99％）。
• Synthetic RCM approaches to enantiopure polyhydroxylated pyrrolizidine alkaloids
  作者：Daniele Muroni、Mauro Mucedda、Antonio Saba

  DOI：10.1016/j.tetlet.2008.02.071

  日期：2008.4

  RCM approach to hindered 5-5-fused bicyclic pyrrolizidine system starting from chiral pyrrolidine, obtained from D-(+)-mannose, has been achieved in convenient yield. (C) 2008 Elsevier Ltd. All rights reserved.
• Proline-based hydroxamates targeting the zinc-dependent deacetylase LpxC: Synthesis, antibacterial properties, and docking studies
  作者：Dmitrii V. Kalinin、Oriana Agoglitta、Hélène Van de Vyver、Jelena Melesina、Stefan Wagner、Burkhard Riemann、Michael Schäfers、Wolfgang Sippl、Bettina Löffler、Ralph Holl

  DOI：10.1016/j.bmc.2019.03.056

  日期：2019.5

  Gram-negative bacteria, which has been validated as antibacterial drug target. Herein we report the chiral-pool synthesis of novel d- and l-proline-derived 3,4-dihydroxypyrrolidine hydroxamates and compare their antibacterial and LpxC inhibitory activities with the ones of 4-monosubstituted and 3,4-unsubstituted proline derivatives. With potent antibacterial activities against several Gram-negative pathogens,

  依赖Zn2 +的脱乙酰基酶LpxC是革兰氏阴性细菌中必不可少的酶，已被确认为抗菌药物的靶标。本文中，我们报道了新颖的d和l-脯氨酸衍生的3,4-二羟基吡咯烷异羟肟酸酯的手性池合成，并将它们的抗菌和LpxC抑制活性与4-单取代和3,4-未取代的脯氨酸衍生物进行了比较。具有对几种革兰氏阴性病原体的有效抗菌活性，基于脯氨酸的叔胺41g（（S）-N-羟基-1-（4-[4-（吗啉代甲基）苯基]乙炔基}苄基）吡咯烷-2 （羧酰胺）被发现是所研究系列中最具活性的抗菌化合物，对几种人类MMP表现出对EcLpxC（Ki = 1.4μM）的选择性。
• Tuning of β-glucosidase and α-galactosidase inhibition by generation and in situ screening of a library of pyrrolidine-triazole hybrid molecules
  作者：Macarena Martínez-Bailén、Ana T. Carmona、Elena Moreno-Clavijo、Inmaculada Robina、Daisuke Ide、Atsushi Kato、Antonio J. Moreno-Vargas

  DOI：10.1016/j.ejmech.2017.06.055

  日期：2017.9

  The preliminary screening of two libraries of epimeric (pyrrolidin-2-yl)triazoles (14a-s and 22a-s), generated via click chemistry, allowed the rapid identification of four alpha-galactosidase (coffee beans) inhibitors (22b,k,p,r) and two beta-glucosidase (almond) inhibitors (14b,f) in the low mu M range. The additional biological analysis of 14b,f towards beta-glucocerebrosidase (human lysosomal beta-glucosidase), as target enzyme for Gaucher disease, showed a good correlation with the inhibition results obtained for the plant (almond) enzyme. Surprisingly, although these compounds showed inhibition towards beta-glucocerebrosidase as acid hydrolase, they did not inhibit bovine liver beta-glucosidase as neutral hydrolase. In contrast to what was observed for beta-glucosidase inhibition, the coffee bean alpha-galactosidase inhibitors of the epimeric library (22b,k,p,r) only showed weak inhibition towards human lysosomal alpha-galactosidase. (C) 2017 Elsevier Masson SAS. All rights reserved.