(S)-α-fluoromethylhistidine

• 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: (S)-α-fluoromethylhistidine
• 英文别名: α-fluoromethyl-histidine；Histidine, alpha-(fluoromethyl)-；(2S)-2-azaniumyl-2-(fluoromethyl)-3-(1H-imidazol-5-yl)propanoate
• 化学式: C₇H₁₀FN₃O₂
• 分子量: 187.174
• InChiKey: AJFGLTPLWPTALJ-SSDOTTSWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.1
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  92
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N_im-trityl-L-histidine N'-methylamide 在 盐酸 、 六甲基磷酰三胺 、 四甲基乙二胺 、 4 A molecular sieve 、 Dowex 50X₈-400 、 水 、 碳酸氢钠 、 sodium carbonate 、 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 129.5h， 生成 (S)-α-fluoromethylhistidine
  参考文献：
  名称：

  A novel stereoselective route to (S)-(+)-.alpha.-(fluoromethyl)histidine: .alpha.-halomethylation of (2R,4S)-3-benzoyl-2-(1,1-dimethylethyl)-1-methyl-4-[(N-tritylimidazol-4-yl)methyl]-1,3-imidazolidin-5-one. Synthesis and proton NMR spectroscopy

  摘要：

  A method is described for the alpha-enantioretentive methylation of L-histidine (S) to give (S)-(+)-alpha-(fluoromethyl)histidine (8). The synthesis involves the conversion of N(im)-trityl-L-histidine methyl ester (1) to both the ''trans''-(2S,4S)- and ''cis''-(2R,4S)-2-(1,1-dimethylethyl)-l-methyl-1,3-imidazolidin-5-one analogs 4 and 5. The cis isomer was regioselectively alkylated with chlorofluoromethane to give a single diastereomer 6 with retention of the original absolute configuration of the histidine alpha-position (S). .Deprotection and hydrolysis of the 1,3-imidazolidin-5-one intermediate 6 yielded the desired (S)-(+)-alpha-(fluoromethyl)histidine (8). Additionally, this reaction sequence was repeated using bromochloromethane as the alkylating agent to yield (S)-(+)-alpha-(chloromethyl)histidine (8a). Yields of this product, however, were very low due to an intramolecular alkylation reaction to give 3-benzoyl-2-(1,1-dimethylethyl)-l-methylspiro[imidazolidine-4,6'(7'H)-[5H]pyrrolo[1,2-c]imidazol]5-one (9). The structure and stereochemistry of the trans and cis 1,3-imidazolidin-5-one intermediates, as well as other members of the series, were confirmed using H-1 NMR spectroscopy, including two-dimensional NOE correlation spectroscopy (2D NOESY). The existence of slow chemical exchange in solution was detected for several members of the series based on the appearance of both positive and negative cross-peaks in the 2D NOESY spectra.

  DOI：

  10.1021/jo00055a027
• 作为试剂：
  描述：

  (S)-α-fluoromethylhistidine dihydrochloride 、 Methylorthoformate 、 1,5-萘二磺酸 在 ice 、 1,5-萘二磺酸 、 (S)-α-fluoromethylhistidine 、 甲醇 、 Methylorthoformate 作用下， 以 甲醇 为溶剂， 反应 37.0h， 以The crystals of (±)-methyl α-fluoromethylhistidinate 1,5-naphthalene disulfonate formed的产率得到(+/-)-methyl α-fluoromethylhistidinate 1,5-naphthalene disulfonate
  参考文献：
  名称：

  Acid addition salts of N-trityl-.alpha.-fluoromethylhistidine enantiomer

  摘要：

  本发明涉及一种处理混合物α-氟甲基组氨酸对映体的方法。该方法采用α-氟甲基组氨酸的酯衍生物。此外，本发明还揭示了该衍生物的新的对映异构体盐。

  公开号：

  US04347374A1

文献信息

• GLUCAGON-LIKE PROTEIN-1 RECEPTOR (GLP-1R) AGONIST COMPOUNDS
  申请人：BRADSHAW Curt W.

  公开号：US20090098130A1

  公开（公告）日：2009-04-16

  The present invention provides GA targeting compounds which comprise GA targeting agent-linker conjugates linked to a combining site of an antibody. Various uses of the compounds are provided, including methods to prevent or treat diabetes or diabetes-related conditions.

  本发明提供了包括连接到抗体结合位点的GA靶向剂-连接剂共轭物的GA靶向化合物。提供了化合物的各种用途，包括预防或治疗糖尿病或与糖尿病相关的疾病的方法。
• [EN] BIOREVERSABLE PROMOIETIES FOR NITROGEN-CONTAINING AND HYDROXYL-CONTAINING DRUGS<br/>[FR] PRO-FRAGMENTS BIORÉVERSIBLES POUR MÉDICAMENTS CONTENANT DE L'AZOTE ET DE L'HYDROXYLE
  申请人：BAIKANG SUZHOU CO LTD

  公开号：WO2015081891A1

  公开（公告）日：2015-06-11

  Disclosed are promoieties of the following formula which can be used to form prodrugs of nitrogen-containing or hydroxyl-containing drug or a pharmaceutically active agent: (I) and pharmaceutical compositions comprising the prodrugs.

  披露了以下公式的促销性质，它们可用于形成含有氮或羟基的药物或药物活性剂的的前药：(I)以及包含这些前药的药物组合物。
• Modified Human Apolipoprotein A-1 and Their Uses
  申请人：Knudsen Nick

  公开号：US20110178029A1

  公开（公告）日：2011-07-21

  Modified human apolipoprotein A-I polypeptides and uses thereof are provided.

  提供了改良的人类载脂蛋白A-I多肽及其用途。
• MODIFIED RELAXIN POLYPEPTIDES AND THEIR USES
  申请人：KRAYNOV Vadim

  公开号：US20120046229A1

  公开（公告）日：2012-02-23

  Modified relaxin polypeptides and their uses thereof are provided

  修改后的弛缓素多肽及其用途
• SUGAR CHAIN-ATTACHED LINKER, COMPOUND CONTAINING SUGAR CHAIN-ATTACHED LINKER AND PHYSIOLOGICALLY ACTIVE SUBSTANCE OR SALT THEREOF, AND METHOD FOR PRODUCING SAME
  申请人：GLYTECH INC.

  公开号：US20150306235A1

  公开（公告）日：2015-10-29

  To provide a carrier linker that is capable of improving the water solubility of a physiologically active substance and more quickly releasing the physiologically active substance under specific conditions without utilizing light or enzymatic cleavage. [Solution]A novel sugar chain-attached linker comprising a sugar chain that is attached as a carrier.

  提供一种载体连接剂，能够提高生理活性物质的水溶性，并在特定条件下更快地释放生理活性物质，而无需利用光或酶解。【解决方案】一种新型的糖链连接剂，包括作为载体附着的糖链。