1,2,3',4'-Tetra-O-acetyl-2',5,6'-tri-O-benzyl-3-O-α-D-glucopyranosyl-D-ribofuranose | 197644-83-0

• 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: 1,2,3',4'-Tetra-O-acetyl-2',5,6'-tri-O-benzyl-3-O-α-D-glucopyranosyl-D-ribofuranose
• 英文别名: Bn(-2)[Bn(-6)]Glc3Ac4Ac(a1-3)[Bn(-5)]Ribf1Ac2Ac；[(2R,3R,4S,5R,6R)-4-acetyloxy-6-[(2R,3R,4R)-4,5-diacetyloxy-2-(phenylmethoxymethyl)oxolan-3-yl]oxy-5-phenylmethoxy-2-(phenylmethoxymethyl)oxan-3-yl] acetate
• CAS: 197644-83-0
• 化学式: C₄₀H₄₆O₁₄
• 分子量: 750.797
• InChiKey: LUZLRRGQJGCXOG-JNGFPJBTSA-N

物化性质

• 沸点：
  779.4±60.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  54
• 可旋转键数：
  21
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  161
• 氢给体数：
  0
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  1,2,3',4'-Tetra-O-acetyl-2',5,6'-tri-O-benzyl-3-O-α-D-glucopyranosyl-D-ribofuranose 在 20percent Pd(OH)2/C ammonium hydroxide 、 三氟甲磺酸三甲基硅酯 、 咪唑 三氟甲磺酸盐 、 间氯过氧苯甲酸 、 环己烯 作用下， 以 甲醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 为溶剂， 反应 42.58h， 生成 Imidophostin
  参考文献：
  名称：

  使用碱基置换策略研究腺嘌呤碱基对腺苷A活性的贡献。

  摘要：

  3'-O-α-D-吡喃葡萄糖基-1-β-D-呋喃呋喃糖基氨基咪唑2'，3''，4''-三磷酸（7）和3'-O-α-D-吡喃葡萄糖基-9-beta的合成描述了-D-呋喃呋喃核糖嘌呤2'，3''，4''-三磷酸（8），这是超强1D-肌醇1,4,5-三磷酸受体激动剂腺苷A（2）的两个类似物。通过改进的路线由1,2-O-异亚丙基-α-D-木呋喃糖制备5-O-苄基-1，2-O-异亚丙基-α-D-呋喃核糖，并与3,4-di-O偶联-乙酰基-2,6-二-O-苄基-D-吡喃葡萄糖基二甲基亚磷酸酯得到3'，4'-二-O-乙酰基-2'，5，6'-三-O-苄基-3-O- α-D-吡喃葡萄糖基-1，2-O-异亚丙基-α-D-呋喃呋喃糖。除去异亚丙基缩醛并随后乙酰化得到中心二糖1,2,3'，4'-四-O-乙酰基-2'，5、6'-三-O-苄基-3-O-α-D-吡喃葡萄糖基-D-呋喃呋喃糖。用活化的咪唑或嘌呤进行弗布吕

  DOI：

  10.1021/jm000265o
• 作为产物：
  描述：

  ethyl 2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranoside 在 吡啶 、 甲醇 、 N-碘代丁二酰亚胺 、 三氟甲磺酸 、 4 A molecular sieve 、 camphor-10-sulfonic acid 、 四丁基氟化铵 、 水 、 sodium methylate 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 乙二醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.5h， 生成 1,2,3',4'-Tetra-O-acetyl-2',5,6'-tri-O-benzyl-3-O-α-D-glucopyranosyl-D-ribofuranose
  参考文献：
  名称：

  Synthesis of Potent Agonists of the d-myo-Inositol 1,4,5-Trisphosphate Receptor Based on Clustered Disaccharide Polyphosphate Analogues of Adenophostin A

  摘要：

  Clustered disaccharide analogues of adenophostin A (2), i.e. mono-, di-, and tetravalent derivatives 6-8, respectively, were synthesized and evaluated as novel ligands for the tetrameric D-myo-inositol 1,4,5-trisphosphate receptor (IP3R). The synthesis was accomplished via Sonogashira coupling of propargyl 2-O-acetyl-5-O-benzyl-3-O-(3,4-di-O-acetyl-2,6-di-O-benzyl-alpha-D-glucopyranosyl)-beta-D-ribofuranoside (16) with iodobenzene 18, 22, or 25, followed by deacetylation, phosphorylation, and deprotection. The abilities of the target compounds 6-8, as well as ribophostin 4, propylphostin 5, and IP3 (1), to evoke Ca2+ release from permeabilized hepatocytes or displacement of [H-3]IP3 from its receptor in hepatic membranes were compared. Although the binding affinities of 4-8 were similar, there were modest though significant differences in their potencies in Ca2+ release assays: tetraphostin 8 > IP3 similar to diphostin 7 > phenylphostin 6 > ribophostin 4 similar to propylphostin 5.

  DOI：

  10.1021/jm000957c

文献信息

• Triazolophostins: a library of novel and potent agonists of IP₃receptors
  作者：Amol M. Vibhute、Vera Konieczny、Colin W. Taylor、Kana M. Sureshan

  DOI：10.1039/c5ob00440c

  日期：——

  IP₃R initiate most cellular Ca²⁺signaling. AdA is the most potent agonist of IP₃R. The structural complexity of AdA makes synthesis of its analogs cumbersome. We report an easy method for generating a library of potent triazole-based analogs of AdA, triazolophostins, which are the most potent AdA analogs devoid of a nucleobase.

  IP3R启动大多数细胞Ca2+信号传导。AdA是IP3R最有效的激动剂。AdA的结构复杂性使其类似物的合成繁琐。我们报告了一种简单的方法，用于生成一系列强效的基于三唑的AdA类似物库，即三唑磷酸酯，它们是最强效的AdA类似物，不含核碱基。
• Convergent synthesis of adenophostin A analogues via a base replacement strategy
  作者：Rachel D. Marwood、Satoshi Shuto、David J. Jenkins、Barry V. L. Potter

  DOI：10.1039/a909347h

  日期：——

  The first totally synthetic base-modified analogues of the natural product and potent D-myo-inositol 1,4,5-trisphosphate receptor agonist adenophostin A were efficiently synthesised from D-xylose and D-glucose using methodology employing base and surrogate base addition to a common disaccharide intermediate.

  天然产物的第一个完全合成的碱基修饰类似物和有效的 D-肌醇 1,4,5-三磷酸受体激动剂腺苷 A 是由 D-木糖和 D-葡萄糖使用碱基和替代碱基添加的方法有效合成的一种常见的二糖中间体。
• Synthesis of Clustered Disaccharide Polyphosphate Analogues of Adenophostin A
  作者：Martin de Kort、A.Rob P.M. Valentijn、Gijs A. van der Marel、Jacques H. van Boom

  DOI：10.1016/s0040-4039(97)01811-x

  日期：1997.10

  Three new potential ligands for the IP3 receptor (i.e. compounds 5–7) were prepared by Sonogashira coupling of propargyl 2-O-acetyl-5-O-benzyl-3-O-(3,4-di-O-acetyl-2,6-di-O-benzyl-α-d- glycopyranosyl)-β-d-ribofuranoside (15) with iodobenzene, 1,2-diiodobenzene and 1,2,4,5-tetraiodobenzene, followed by deacetylation, phosphorylation and deprotection. © 1997 Elsevier Science Ltd.

  通过炔丙基2 - O-乙酰基-5- O-苄基-3- O-（3,4-二-O-乙酰基- ）的Sonogashira偶联，制备了IP 3受体的三个新的潜在配体（即化合物5-7）。2,6-二-O-苄基-α-d-吡喃葡萄糖基）-β-d-呋喃核糖苷（15）与碘苯，1,2-二碘苯和1,2,4,5-四碘苯，然后进行脱乙酰基化，磷酸化和脱保护。©1997爱思唯尔科学有限公司。
• Guanophostin A: Synthesis and evaluation of a high affinity agonist of the d-myo-inositol 1,4,5-trisphosphate receptor
  作者：Kana M. Sureshan、Melanie Trusselle、Stephen C. Tovey、Colin W. Taylor、Barry V. L. Potter

  DOI：10.1039/b517911d

  日期：——

  Guanophostin A, the guanosine counterpart of the inositol 1,4,5-trisphosphate receptor agonist adenophostin A, has been synthesized and is the first synthetic adenophostin A-like analogue to be equipotent to its parent in stimulating intracellular Ca2+ release; its nucleotide moiety is proposed to interact with the receptor binding core by guanine base cation-π stacking with Arg504 and hydrogen bonding with Glu505 and interaction of the ribosyl 2′-phosphate group with the helix-dipole of α6.

  Guanophostin A 是 1,4,5-三磷酸肌醇受体激动剂腺苷 A 的鸟苷对应物，已被合成，它是第一个在刺激细胞内 Ca2+ 释放方面与其母体等效的合成腺苷 A 类似物；据推测，其核苷酸分子通过鸟嘌呤基阳离子-π堆叠与 Arg504、氢键与 Glu505 以及核糖基 2′-磷酸基团与 α6 的螺旋偶极相互作用，与受体结合核心相互作用。
• Total Synthesis of Nucleobase-Modified Adenophostin A Mimics
  作者：Satoshi Shuto、Graeme Horne、Rachel D. Marwood、Barry V. L. Potter

  DOI：10.1002/1521-3765(20011119)7:22<4937::aid-chem4937>3.0.co;2-g

  日期：2001.11.19

  The adenophostins exhibit approximately 10-100 times higher receptor binding and Ca2+ mobilising potencies in comparison with the natural second messenger D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3]. Despite many synthetic attempts to determine the minimal structural requirement for this unusual behaviour of the adenophostins, few related simplified analogues displaying higher activity than that of Ins(1.4,5)P-3 have been reported. However, biological evaluation of such analogues has revealed that one of the key factors for the enhanced biological activity is the adenine moiety. To further understand the effect that the adenine base has upon the activity of the adenophostins, congeners in which this functionality is replaced by uracil, benzimidazole, 2-methoxynaphthalene, 4-methylanisole and 4-methylnaphthalene using the common intermediate 1,2-di-O-acetyl-5-O-benzyl-3-O-(3,4-di-O-acetyl-2,6-di-O-benzyl-alpha -D-glucopyranosyl)-ribofuranose have been synthesised using a base replacement strategy. The synthesis of the uracil and benzimidazole analogues was achieved using the Vorbruggen condensation procedure. The 1'-C-glycosidic analogues were prepared using Friedel-Crafts type C-aryl glycosidation reactions. Phosphate groups were introduced using the phosphoramidite method with subsequent removal of all-benzyl protecting groups by catalytic hydrogenation or catalytic hydrogen transfer. Apart from one analogue with an alpha -glycosidic linkage all compounds were more potent than Ins(1,4,5)P-3 and most tended more towards adenophostin in activity. These analogues will be valuable tools to unravel the role that the adenine moiety plays in the potent activity of the adenophostins and demonstrate that this strategy is effective at producing highly potent ligands.