N,N'-di-tert-butoxycarbonyl-D,L-homocystine | 1082927-67-0

• 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: N,N'-di-tert-butoxycarbonyl-D,L-homocystine
• 英文别名: 2-(R,S)-9-(R,S)-2,9-bis(tert-butoxycarbonylamino)-5,6-dithiadecanedioic acid；4,4'-disulfanediylbis(2-((tert-butoxycarbonyl)amino)butanoic acid)；4-[[3-Carboxy-3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]disulfanyl]-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid
• CAS: 1082927-67-0
• 化学式: C₁₈H₃₂N₂O₈S₂
• 分子量: 468.593
• InChiKey: JXQOESIPFURHKL-UHFFFAOYSA-N

物化性质

• 熔点：
  161-163 °C
• 沸点：
  666.3±55.0 °C(Predicted)
• 密度：
  1.272±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  202
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  N,N'-di-tert-butoxycarbonyl-D,L-homocystine 在 三丁基膦 、 sodium hydride 、 氯乙酸乙酯 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.17h， 生成 tert-butyl 5-[3-(R,S)-3-(tert-butoxycarbonylamino)-4-oxo-4-(piperidin-1-yl)butylsulfanyl]pentanoate
  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
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 三乙胺 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 4.75h， 生成 N,N'-di-tert-butoxycarbonyl-D,L-homocystine
  参考文献：
  名称：

  Efficient and Scalable Syntheses of 1,2-Thiaselenane-4-amine and 1,2-Thiaselenane-5-amine

  摘要：

  摘要：首次开发了1,2-硫-硒杂环-4-胺（TSA4）和1,2-硫-硒杂环-5-胺（TSA5）的区域选择性合成。这两种化合物是具有高化学生物学价值的氧化还原基团，但由于繁琐的合成而受到阻碍。通过利用环氧乙烷中间体和动力学控制的S-酰化反应，实现了区域选择性的硫、硒元素安装。优化了简短、快速的合成步骤，仅需一两个色谱步骤即可廉价地制备这些基团，用于高通量抑制剂筛选，并提供了组装其他硒烯基硫化物的稳健方法。

  DOI：

  10.1055/a-2022-1398

文献信息

• SAH derived potent and selective EZH2 inhibitors
  作者：Pei-Pei Kung、Buwen Huang、Luke Zehnder、John Tatlock、Patrick Bingham、Cody Krivacic、Ketan Gajiwala、Wade Diehl、Xiu Yu、Karen A. Maegley

  DOI：10.1016/j.bmcl.2015.02.017

  日期：2015.4

  the histone methyltransferase (HMT) inhibitor SAH (S-adenosyl-l-homocysteine). These nucleoside-based EZH2 inhibitors blocked the methylation of nucleosomes at H3K27 in biochemical assays employing both WT PRC2 complex as well as a Y641N mutant PRC2 complex. The most potent compound, 27, displayed IC50’s against both complexes of 270 nM and 70 nM, respectively. To our knowledge, compound 27 is the most

  基于组蛋白甲基转移酶（HMT）抑制剂SAH（S-腺苷-1-同型半胱氨酸）的化学结构，设计了一系列新型的zeste同源物2（EZH2）抑制剂增强剂。这些基于核苷的EZH2抑制剂在同时使用WT PRC2复合物和Y641N突变体PRC2复合物的生化分析中阻止了H3K27处核小体的甲基化。最有效的化合物27对两种复合物分别显示270 nM和70 nM的IC 50值。据我们所知，化合物27是尚未发现的最有效的SAH衍生的EZH2 PRC2复合物的抑制剂。与SAH相比，该化合物还显示出更高的效价，亲脂效率（LipE）和对其他赖氨酸甲基转移酶的选择性。
• [EN] RADIOLABELED FLUORINE DERIVATIVES OF METHIONINE<br/>[FR] DÉRIVÉS DE LA MÉTHIONINE RADIOMARQUÉS AU FLUOR
  申请人：CRC FOR BIOMEDICAL IMAGING DEV

  公开号：WO2010108210A1

  公开（公告）日：2010-09-30

  The invention provides compound which is an 18F-radiolabelled S-propylhomocysteine or a derivative thereof. The compound has an enantiomeric purity of at least about 90%. 18F- radiolabelled S-propylhomocysteine may be made by treating an N-protected ester of a substituted S-propylhomocysteine with a complexed F" salt in the presence of a base to form a protected product and then deprotecting the protected product to form the 18F- radiolabelled S-propylhomocysteine. In this method the N-protected ester has a leaving group on the S-propyl group and has an enantiomeric purity of at least about 90%. The base should be such that it does not cause racemisation of the protected product.

  该发明提供了一种18F-放射标记的S-丙基同型半胱氨酸化合物或其衍生物。该化合物的对映纯度至少为约90%。18F-放射标记的S-丙基同型半胱氨酸可以通过处理取代的S-丙基同型半胱氨酸的N-保护酯与复合F"盐在碱存在下形成保护产物，然后去保护产物以形成18F-放射标记的S-丙基同型半胱氨酸来制备。在这种方法中，N-保护酯在S-丙基基团上有一个离去基团，并且其对映纯度至少为约90%。碱应该是不会导致保护产物发生外消旋的碱。
• Synthesis of chemotaxic tripeptide analogs containing L- and D-(S-trifluoromethyl)-homocysteine and having hypotensive activity
  作者：V. V. Ryakhovskii、S. V. Agafonov、O. B. Vinogradova、Yu. M. Kosyrev、M. V. Kiselevskii、V. S. Dobryanskii

  DOI：10.1007/bf00766457

  日期：1992.2