tribenzyl hydrogen methylenebis(phosphonate) | 7292-39-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: tribenzyl hydrogen methylenebis(phosphonate)
• 英文别名: [[bis(benzyloxy)phosphoryl]methyl]phosphonic acid monobenzyl ester；<methyl>phosphonic acid monobenzyl ester；methylenebisphosphonic acid tribenzyl ester；benzyl hydrogen ((bis(benzyloxy)phosphoryl)methyl)phosphonate；tribenzyl methylene diphosphate；Bis(phenylmethoxy)phosphorylmethyl-phenylmethoxyphosphinic acid
• CAS: 7292-39-9
• 化学式: C₂₂H₂₄O₆P₂
• 分子量: 446.376
• InChiKey: PFXFLOLHNLCWIV-UHFFFAOYSA-N

物化性质

• 熔点：
  90-92 °C
• 沸点：
  619.5±65.0 °C(Predicted)
• 密度：
  1.306±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tribenzyl hydrogen methylenebis(phosphonate) 在 盐酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 1.5h， 生成 thiamine α:β-methylenediphosphate tribenzyl ester
  参考文献：
  名称：

  Synthesis of Stable Analogues of Thiamine Di- and Triphosphate as Tools for Probing a New Phosphorylation Pathway

  摘要：

  Thiamine (vitamin B1) is an essential nutritional factor metabolized inside the body in its mono-, di-, and triphosphate forms. Although the action of thiamine and thiamine diphosphate have been intensely investigated, many questions remain unanswered and the role of thiamine triphosphate is still especially unknown. To probe recent hypotheses on the implication of thiamine triphosphate in a new phosphorylation pathway involving synaptic proteins, we synthesized a series of thiamine di- and triphosphate analogues that are resistant to both enzymatic and chemical hydrolyses. The key step in the preparation of the title compounds is the coupling of thiamine propyl disulfide with adequately protected methylenebisphosphonic acid, the corresponding triphosphate analogue, and difluoromethylenebisphosphonic acid.

  DOI：

  10.1002/1521-3765(20021018)8:20<4649::aid-chem4649>3.0.co;2-m
• 作为产物：
  描述：

  亚磷酸二苄酯 在 三乙烯二胺 、 四溴化碳 、 三乙胺 、 三苯基膦 作用下， 以 甲苯 、 乙腈 为溶剂， 20.0~140.0 ℃ 、133.32 Pa 条件下， 反应 24.0h， 生成 tribenzyl hydrogen methylenebis(phosphonate)
  参考文献：
  名称：

  The assembly of β-methylene-TAD, a metabolically stable analogue of the antitumor agent tad, by the stepwise esterification of monodeprotected methylenebis-(phosphonate) benzyl esters under mitsunobu conditions

  摘要：

  Synthesis of the metabolically stable analogue of thiazole-4-carboxamide adenine dinucleotide (beta-methylene-TAD) was achieved via the sequential monodeprotection of tetrabenzyl methylenebis(phosphonate) after two rounds of Mitsunobu esterifications with the corresponding nucleoside components, tiazofurin and adenosine. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00544-2
• 作为试剂：
  描述：

  三甲基氰硅烷 、 、 4-amino-N-(4-heptylphenyl)butanamide 在 tribenzyl hydrogen methylenebis(phosphonate) 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以16.7 mg的产率得到
  参考文献：
  名称：

  [EN] GLYCOSYLTRANSFERASE INHIBITORS
  [FR] INHIBITEURS DE GLYCOSYLTRANSFÉRASE

  摘要：

  本发明涉及治疗细菌感染和癌症的方法，包括向需要治疗的受体中注射本申请书中提供的至少一种化合物的治疗有效量。还提供了一种抑制需要DPAGT1的个体中的多聚糖磷酸N-乙酰葡萄糖胺磷酸转移酶（DPAGT1）的方法，包括向需要治疗的个体中注射本申请书中描述的任何一种化合物或组合物的治疗有效量。

  公开号：

  WO2019140158A1

文献信息

• Synthesis of Enzymatically Stable Analogues of GDP for Binding Studies with Transducin, the G-Protein of the Visual Photoreceptor
  作者：Stéphane Vincent、Sonya Grenier、Alain Valleix、Christian Salesse、Luc Lebeau、Charles Mioskowski

  DOI：10.1021/jo9806207

  日期：1998.10.1

  final deprotection step was achieved by catalytic hydrogenolysis. The biological properties of the compounds have been evaluated toward transducin, the G-protein of the visual photoreceptor. Three guanosine imidodiphosphate derivatives bearing a linker at different positions on the sugar and on the base were then prepared and evaluated, giving some insight into the GDP binding site of transducin.

  进行了五种鸟嘌呤二磷酸鸟嘌呤（GDP）的酶促稳定类似物的合成。焦磷酸部分依次被丙二酸酯，乙酰膦酸酯，膦酰基乙酸酯，亚甲基双膦酸酯和亚氨基二磷酸酯基团模拟。所有化合物都是通过合成一个瞬态完全保护的核苷二磷酸类似物来制备的，最后的脱保护步骤是通过催化氢解来实现的。已针对视觉感光器的G蛋白转导素评估了化合物的生物学特性。然后制备并评估了三种在糖上和碱基上不同位置带有连接子的鸟嘌呤亚氨基二磷酸衍生物，从而对转导蛋白的GDP结合位点有所了解。
• [EN] COMPOSITIONS AND METHODS OF MODULATING THE IMMUNE RESPONSE BY ACTIVATING ALPHA PROTEIN KINASE 1<br/>[FR] COMPOSITIONS ET PROCÉDÉS DE MODULATION DE LA RÉPONSE IMMUNITAIRE PAR ACTIVATION DE LA PROTÉINE KINASE ALPHA 1
  申请人：SHANGHAI YAO YUAN BIOTECHNOLOGY CO LTD

  公开号：WO2019080898A1

  公开（公告）日：2019-05-02

  The disclosure provides compositions and methods related to activating alpha-kinase 1 (ALPK1) for modulating an immune response and treating or preventing cancer, infection, inflammation and related diseases and disorders as well as potentiating an immune response to a target antigen. The disclosure also provides heterocyclic compounds of formula (I) as agonists of alpha protein kinase 1 (ALPK1) and their use in activating ALPK1, modulating an immune response and treating diseases such as cancer, wherein A1, A2, L1, L2, L3, Z1, Z2, W1, W2, R1, R2, R3, R4, R5, R6 and R7 are defined herein.

  该披露提供了与激活α-激酶1（ALPK1）相关的组合物和方法，用于调节免疫应答，治疗或预防癌症、感染、炎症和相关疾病和疾病，以及增强对靶抗原的免疫应答。该披露还提供了式（I）的杂环化合物作为α蛋白激酶1（ALPK1）的激动剂，并其在激活ALPK1、调节免疫应答和治疗癌症等疾病中的应用，其中A1、A2、L1、L2、L3、Z1、Z2、W1、W2、R1、R2、R3、R4、R5、R6和R7在此定义。
• First Use of Benzyl Phosphites in theMichaelis-Arbuzov Reaction synthesis of mono-, Di-, and triphosphate analogs
  作者：Mourad Saady、Luc Lebeau、Charles Mioskowski

  DOI：10.1002/hlca.19950780314

  日期：1995.5.10

  Micaelis-Arbuzov reaction. Special experimental conditions allowed preparation of a set of phosphonate analogs of mono-, di-, and triphosphate. Furthermore, regioselective monodeprotection makes these molecules useful building blocks for the synthesis of analogs of polyphosphorylated compounds of biological interest (e.g. nucleotides), after removal of all phosphonate benzyl ester groups under very

  亚甲基苄基酯用于Micaelis-Arbuzov反应。特殊的实验条件允许制备一组单磷酸，二磷酸和三磷酸的膦酸酯类似物。此外，在非常温和的条件下以高收率除去所有膦酸酯苄酯基团之后，区域选择性单脱保护使这些分子成为合成具有生物学意义的多磷酸化化合物（例如核苷酸）的类似物的有用组成部分。
• Synthesis and evaluation of stable substrate analogs as potential modulators of cyclodiphosphate synthase IspF
  作者：J. Kipchirchir Bitok、Caren Freel Meyers

  DOI：10.1039/c2md20175e

  日期：——

  Stable IspF substrate analogs display distinct and unexpected properties as modulators of IspF and IspF–MEP activities.

  稳定的IspF底物类似物展现出作为IspF和IspF-MEP活性调节剂的独特和意想不到的性质。
• Compositions and methods of modulating the immune response by activating alpha protein kinase 1
  申请人：Shanghai Yao Yuan Biotechnology Co., Ltd.

  公开号：US11149051B2

  公开（公告）日：2021-10-19

  The disclosure provides compositions and methods related to activating alpha-kinase 1 (ALPK1) for modulating an immune response and treating or preventing cancer, infection, inflammation and related diseases and disorders as well as potentiating an immune response to a target antigen. The disclosure also provides heterocyclic compounds of formula (I) as agonists of alpha protein kinase 1 (ALPK1) and their use in activating ALPK1, modulating an immune response and treating diseases such as cancer, wherein A1, A2, L1, L2, L3, Z1, Z2, W1, W2, R1, R2, R3, R4, R5, R6 and R7 are defined herein.

  本公开提供了与激活α蛋白激酶1（ALPK1）有关的组合物和方法，用于调节免疫反应和治疗或预防癌症、感染、炎症及相关疾病和失调，以及增强对靶抗原的免疫反应。本公开还提供了作为α蛋白激酶1（ALPK1）激动剂的式(I)杂环化合物及其在激活ALPK1、调节免疫应答和治疗癌症等疾病中的用途，其中A1、A2、L1、L2、L3、Z1、Z2、W1、W2、R1、R2、R3、R4、R5、R6和R7在本文中定义。