(2S,4R)-4-(benzyloxy)-1-((benzyloxy)carbonyl)pyrrolidine-2-carboxylic acid | 73004-31-6

• 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: (2S,4R)-4-(benzyloxy)-1-((benzyloxy)carbonyl)pyrrolidine-2-carboxylic acid
• 英文别名: trans-4-benzyloxy-N-Cbz-L-proline；(2S,4R)-4-phenylmethoxy-1-phenylmethoxycarbonylpyrrolidine-2-carboxylic acid
• CAS: 73004-31-6
• 化学式: C₂₀H₂₁NO₅
• 分子量: 355.39
• InChiKey: WNRGTKVCQYDRKL-MSOLQXFVSA-N

物化性质

• 沸点：
  538.7±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,4R)-4-(benzyloxy)-1-((benzyloxy)carbonyl)pyrrolidine-2-carboxylic acid 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 草酰氯 、 氢气 、 silver(I) acetate 、 potassium carbonate 、 三乙胺 、 三苯基膦 、 potassium iodide 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 201.5h， 生成 (1S,5S)-6-(4,4-diphenylbut-3-en-1-yl)-2-oxa-6-azabicyclo[3.2.1]octan-3-one
  参考文献：
  名称：

  Synthesis and biological evaluation of new GABA-uptake inhibitors derived from proline and from pyrrolidine-2-acetic acid

  摘要：

  Several synthetic approaches to N-alkylated derivatives of 4-hydroxypyrrolidine-2-carboxylic acid and 4-hydroxypyrrolidine-2-acetic acid are described. The final compounds have been evaluated as potential inhibitors of the GABA transport proteins GAT-I and GAT-3. The biological assays used were based on bovine material or porcine brain. As compared to the corresponding 4-unsubstituted compounds, the 4-hydroxypyrrolidine-2-carboxylic acid and 4-hydroxypyrrolidine-2-acetic acid derivatives showed a significant decrease in the inhibitory potency at both GAT-1 and GAT-3 with only four compounds having reasonable affinity to GAT-1 (IC50: 5.1, 6.6 and 9.4 mu M) or GAT-3 (IC50:19.9 mu M), respectively. The biological data of the 4-hydroxypyrrolidine-2-acetic acid derivatives indicates that (2S)-configuration at the C-2 position for potent inhibition of GAT-1 and (4R)-configuration at the C-4 position for potent inhibition of GAT-3 may be crucial. (c) 2005 Elsevier SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2004.11.004
• 作为产物：
  描述：

  L-羟基脯氨酸 在 sodium hydride 、 碳酸氢钠 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 24.0h， 生成 (2S,4R)-4-(benzyloxy)-1-((benzyloxy)carbonyl)pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  N-保护烷氧基脯氨酸在特定溶剂化条件下的化学选择性合成

  摘要：

  N-保护的羟脯氨酸 (Hyp) 通过直接 O-烷基化被化学选择性地转化为烷氧基脯氨酸衍生物。在作为溶剂的二甲基亚砜和四氢呋喃 (1:16 v/v) 的混合物中，起始的 Hyp 被转化为相应的二价阴离子。在这些条件下，羧基阴离子显示出降低的亲核性，因为它被特异性地溶剂化，而更具反应性的氧阴离子被选择性地烷基化。N-保护的反-4-烷氧基-、顺-4-烷氧基-和反-3-烷氧基脯氨酸因此以非常高的总产率和立体中心构型的完全稳定性在单个步骤中获得。

  DOI：

  10.1002/ejoc.201402429

文献信息

• Aminal-Pyrrolidine Organocatalysts - Highly Efficient and Modular Catalysts for α-Functionalization of Carbonyl Compounds
  作者：Adrien Quintard、Sébastien Belot、Estelle Marchal、Alexandre Alexakis

  DOI：10.1002/ejoc.200901283

  日期：2010.2

  2-position, gave a synergistic effect leading to two powerful complementary organocatalysts. They show excellent enantiocontrol in the -functionalization of a wide range of linear/branched aldehydes and ketones, including Michael additions to ethenediyl disulfones or nitrostyrene and -amination. We obtained ees up to 98.5 % with low catalyst loadings (down to 1 mol-%). As a proof of efficiency, TOFs of up to

  羟基脯氨酸的 4-位被 aphenol 基团取代，连同 2-位上的氨基，产生协同效应，产生两种强大的互补有机催化剂。它们在广泛的线性/支化醛和酮的 - 官能化中表现出出色的对映控制，包括迈克尔加成到乙二基二砜或硝基苯乙烯和 - 胺化。我们以低催化剂负载量（低至 1 mol%）获得了高达 98.5% 的 ees。作为效率的证明，可以获得高达 1000 h-1 的 TOF。
• Synthesis and biological evaluation of febrifugine analogues as potential antimalarial agents
  作者：Shuren Zhu、Quan Zhang、Chandrashekar Gudise、Lai Wei、Erika Smith、Yuling Zeng

  DOI：10.1016/j.bmc.2009.05.011

  日期：2009.7

  Febrifugine is an alkaloid isolated from Dichroa febrifuga Lour as the active component against Plasmodium falciparum. Adverse side effects have precluded febrifugine as a potential clinical drug. In this study novel febrifugine analogues were designed and synthesized. Lower toxicity was achieved by reducing or eliminating the tendency of forming chemically reactive and toxic intermediates and metabolites

  Febrifugine 是一种从Dichroa febrifuga Lour 中分离出来的生物碱，是对抗恶性疟原虫的活性成分. 不良副作用已排除 febrifugine 作为潜在的临床药物。在这项研究中，设计并合成了新的发热剂类似物。通过减少或消除形成化学反应性和有毒中间体和代谢物的趋势来实现较低的毒性。对合成化合物的急性毒性和体外和体内抗疟功效进行了评估。一些化合物的毒性远低于天然产物 febrifugine 和现有的抗疟药氯喹，预计具有较宽的治疗窗。这些化合物以及潜在的设计原理可能有助于发现和开发新的抗疟药。
• Synthesis and pharmacological activity of angiotensin-converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines
  作者：Elizabeth M. Smith、Gerald F. Swiss、Bernard R. Neustadt、Elijah H. Gold、Jane A. Sommer、Arthur D. Brown、Peter J. S. Chiu、Rosa Moran、Edmund J. Sybertz、Thomas Baum

  DOI：10.1021/jm00399a033

  日期：1988.4

  The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.
• Discovery of inhibitors of the channel-activating protease prostasin (CAP1/PRSS8) utilizing structure-based design
  作者：David C. Tully、Agnès Vidal、Arnab K. Chatterjee、Jennifer A. Williams、Michael J. Roberts、H. Michael Petrassi、Glen Spraggon、Badry Bursulaya、Reynand Pacoma、Aaron Shipway、Andrew M. Schumacher、Henry Danahay、Jennifer L. Harris

  DOI：10.1016/j.bmcl.2008.08.029

  日期：2008.11

  Structure-based design was utilized to guide the early stage optimization of a substrate-like inhibitor to afford potent peptidomimetic inhibitors of the channel-activating protease prostasin. The first X-ray crystal structures of prostasin with small molecule inhibitors bound to the active site are also reported.
• SMITH, ELIZABETH M.;SWISS, GERALD F.;NEUSTADT, BERNARD R.;GOLD, ELIJAH H.+, J. MED. CHEM., 31,(1988) N 4, 875-885
  作者：SMITH, ELIZABETH M.、SWISS, GERALD F.、NEUSTADT, BERNARD R.、GOLD, ELIJAH H.+

  DOI：——

  日期：——