tert-butyl (2S,4S)-4-acetylthio-1-[(tert-butyl)oxycarbonyl]pyrrolidine-2-carboxylate | 335280-26-7

• 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: tert-butyl (2S,4S)-4-acetylthio-1-[(tert-butyl)oxycarbonyl]pyrrolidine-2-carboxylate
• 英文别名: tert-butyl (2S,4S)-N-tert-butoxycarbonyl-4-thioacetoxyprolinate；ditert-butyl (2S,4S)-4-acetylsulfanylpyrrolidine-1,2-dicarboxylate
• CAS: 335280-26-7
• 化学式: C₁₆H₂₇NO₅S
• 分子量: 345.46
• InChiKey: ONJOEPMCGIBVML-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  98.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl (2S,4S)-4-acetylthio-1-[(tert-butyl)oxycarbonyl]pyrrolidine-2-carboxylate 在 palladium on activated charcoal 盐酸 、 氨 、 氢气 、 sodium hydride 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、310.26 kPa 条件下， 反应 53.42h， 生成 (4S)-4-[[2-[(1-iminoethyl)amino]ethyl]thio]-L-proline
  参考文献：
  名称：

  合成新的构象受限 S-[2-[(1-亚氨基乙基)氨基]乙基]高半胱氨酸衍生物作为潜在的一氧化氮合酶抑制剂

  摘要：

  两种新型构象受限的S-[2-[(1-亚氨基乙基)氨基]乙基]高半胱氨酸衍生物1-氨基-3-[2[(1-亚氨基乙基)氨基]乙硫基]环丁烷羧酸的高效合成( 5) 和 (4S)-4-[[2-[(1-亚氨基乙基)氨基]乙基]硫代]-L-脯氨酸(6)，被报道。这些分子代表了首次尝试探索已知的基于同型半胱氨酸的一氧化氮合酶抑制剂的 α-氨基酸部分附近的构象约束。目标 5 和 6 被评估为一氧化氮合酶的三种人类亚型的潜在抑制剂。© 2002 John Wiley & Sons, Inc. 杂原子化学 13:77–83, 2002; DOI 10.1002/hc.1109

  DOI：

  10.1002/hc.1109
• 作为产物：
  描述：

  L-羟基脯氨酸 在 吡啶 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 114.0h， 生成 tert-butyl (2S,4S)-4-acetylthio-1-[(tert-butyl)oxycarbonyl]pyrrolidine-2-carboxylate
  参考文献：
  名称：

  The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase

  摘要：

  Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely define the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.039

文献信息

• The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase
  作者：Jan Pícha、Václav Vaněk、Miloš Buděšínský、Jana Mládková、Timothy A. Garrow、Jiří Jiráček

  DOI：10.1016/j.ejmech.2013.04.039

  日期：2013.7

  Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely define the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Syntheses of new conformationally constrainedS-[2-[(1-iminoethyl)amino] ethyl]homocysteine derivatives as potential nitric oxide synthase inhibitors
  作者：Lijuan J. Wang、Margaret L. Grapperhaus、Barnett S. Pitzele、Timothy J. Hagen、Kam F. Fok、Jeffrey A. Scholten、Dale P. Spangler、Mihaly V. Toth、Gina M. Jerome、William M. Moore、Pamela T. Manning、James A. Sikorski

  DOI：10.1002/hc.1109

  日期：——

  The efficient syntheses of two new types of conformationally constrained S-[2-[(1-iminoethyl)amino]ethyl]homocysteine derivatives, 1-amino-3-[2[(1-iminoethyl)amino]ethylthio]cyclobutane carboxylic Acid (5) and (4S)-4-[[2-[(1-Iminoethyl)amino]ethyl]thio]-L-proline (6), are reported. These molecules represent the first attempts to probe conformational constraint near the α-amino acid moiety of known

  两种新型构象受限的S-[2-[(1-亚氨基乙基)氨基]乙基]高半胱氨酸衍生物1-氨基-3-[2[(1-亚氨基乙基)氨基]乙硫基]环丁烷羧酸的高效合成( 5) 和 (4S)-4-[[2-[(1-亚氨基乙基)氨基]乙基]硫代]-L-脯氨酸(6)，被报道。这些分子代表了首次尝试探索已知的基于同型半胱氨酸的一氧化氮合酶抑制剂的 α-氨基酸部分附近的构象约束。目标 5 和 6 被评估为一氧化氮合酶的三种人类亚型的潜在抑制剂。© 2002 John Wiley & Sons, Inc. 杂原子化学 13:77–83, 2002; DOI 10.1002/hc.1109