2',3'-di-O-acetylinosine | 4152-78-7

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2',3'-di-O-acetylinosine
• 英文别名: 2a(2),3a(2)-Di-O-acetylinosine；[(2R,3R,4R,5R)-4-acetyloxy-2-(hydroxymethyl)-5-(6-oxo-1H-purin-9-yl)oxolan-3-yl] acetate
• CAS: 4152-78-7
• 化学式: C₁₄H₁₆N₄O₇
• 分子量: 352.304
• InChiKey: DVOGFRUBRPQKOL-IDTAVKCVSA-N

物化性质

• 熔点：
  215 °C
• 沸点：
  631.0±65.0 °C(Predicted)
• 密度：
  1.72±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  141
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2',3'-di-O-acetylinosine 在 ammonium hydroxide 、 四氧化锇 、 三氟化硼乙醚 、 双氧水 作用下， 以 四氢呋喃 、 丙酮 、 叔丁醇 为溶剂， 反应 24.0h， 生成 α-D-mannopyranosyl-(1->5)-inosine
  参考文献：
  名称：

  Syntheses of 5′-O-glycosylnucleosides

  摘要：

  A general synthetic approach to 2,3-unsaturated glycosides connecting with nucleosides involving Ferrier rearrangements of glycals is discussed. The new compounds were identified by NMR and MS (HRFAB(+)). The hydroxylation of the resulting 2,3-unsaturated glycosides was completed using OsO4 to give 5'-O-glycosylnucleosides in good yield. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(99)00214-1
• 作为产物：
  描述：

  2',3',5'-三乙酰腺苷 在 偶氮二甲酰胺 作用下， 以 phosphate buffer 、 水 、 丙酮 为溶剂， 反应 30.0h， 生成 2',3'-di-O-acetylinosine
  参考文献：
  名称：

  腺苷脱氨酶（EC 3.5.4.4。）对腺苷和脱氧腺苷乙酸酯的作用：5'-羟基对酶活性的关键作用

  摘要：

  从腺苷1，2'-脱氧腺苷3和3'-脱氧腺苷5个所有乙酸盐是由脂肪酶催化的反应制备。只有带有游离5'-羟基的乙酸盐才被腺苷脱氨酶（ADA）脱氨，这证实了5'-OH对酶活性的关键作用。

  DOI：

  10.1016/s0040-4020(00)00222-2
• 作为试剂：
  描述：

  N-acetyl-4,7,8,9-tetra-O-acetyl-2-chloro-2-deoxyneuraminic acid methyl ester 在 4 A molecular sieve 、 silver trifluoromethanesulfonate 、 2',3'-di-O-acetylinosine 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以9.3%的产率得到methyl onate
  参考文献：
  名称：

  Studies on sialic acids. XI. Synthesis of 2-O-glycosyl derivatives of N-acetylneuraminic acid.

  摘要：

  甲基N-乙酰基-4,7,8,9-四-O-乙酰基-2-氯-2-脱氧-β-D-神经氨酸（2）与2',3'-二-O-乙酰基肌苷（1）和2',3'-二-O-乙酰基-N-苯甲酰胞苷（8）在Koenigs-KOnorr类反应条件下的反应分别得到相应的（2→5）连接二糖核苷酸类似物，产率分别为31%和23%。这些核苷酸5'-N-乙酰神经氨酸类似物通过皂化或氨解转化为最终目标化合物。通过分析质子核磁共振（1H-NMR）光谱和测量（2→5）糖苷键的水解速率，证实了这些化合物的立体化学。

  DOI：

  10.1248/cpb.36.914

文献信息

• Structure-activity relationship of leucyladenylate sulfamate analogues as leucyl-tRNA synthetase (LRS)-targeting inhibitors of Mammalian target of rapamycin complex 1 (mTORC1)
  作者：Suyoung Yoon、Sung-Eun Kim、Jong Hyun Kim、Ina Yoon、Phuong-Thao Tran、Jihyae Ann、Changhoon Kim、Woong Sub Byun、Sangkook Lee、Sunghoon Kim、Jiyoun Lee、Jeewoo Lee

  DOI：10.1016/j.bmc.2019.01.037

  日期：2019.3

  Leucyl-tRNA synthetase (LRS) plays an important role in amino acid-dependent mTORC1 signaling, which is known to be associated with cellular metabolism and proliferation. Therefore, LRS-targeting small molecules that can suppress mTORC1 activation may provide an alternative strategy to current anticancer therapy. In this work, we developed a library of leucyladenylate sulfate analogues by extensively

  Leucyl-tRNA合成酶（LRS）在氨基酸依赖性mTORC1信号传导中起重要作用，已知该信号与细胞代谢和增殖有关。因此，可以抑制mTORC1激活的靶向LRS的小分子可以为当前的抗癌治疗提供替代策略。在这项工作中，我们通过广泛修饰包括腺嘌呤，核糖和亮氨酸的三个不同药效学区域，开发了硫酸亮环烯丙酸酯类似物的文库。通过基于细胞的mTORC1活化分析鉴定了几种有效的化合物，并进一步测试了其抗癌活性。选定的化合物大部分对五种不同的癌细胞系表现出选择性的细胞毒性，支持以下假设：LRS介导的mTORC1途径是当前治疗方法的有希望的替代靶点。
• A Simple Enzymatic Preparation of 2’,3’-Di-OAcetylnucleosides Through a Lipase Catalyzed Alcoholysis
  作者：Alejandra Zinni、Alejandro Schmidt、Mariana Gallo、Luis Iglesias、Adolfo Iribarren

  DOI：10.3390/50300533

  日期：——

  Several 2’,3’-di-O-acetylnucleosides (2a-d) were obtained regioselectively through a Candida antarctica B lipase catalyzed alcoholysis.

  几种 2',3'-二-O-乙酰基核苷（2a-d）是通过白色念珠菌 B 脂肪酶催化醇解而获得的。
• Induction of suppressor T cells by neuraminic acid derivatives.
  作者：ISAO KIJIMA、KUNIO EZAWA、SATOSHI TOYOSHIMA、KIMIO FURUHATA、HARUO OGURA、TOSHIAKI OSAWA

  DOI：10.1248/cpb.30.3278

  日期：——

  We investigated the effects of α- and β-methylglycosides of N-acetylneuraminic acid and its disaccharide derivatives on the proliferation and immunological functions of murine lymphocytes. The Con A-induced increase of deoxyribonucleic acid (DNA) synthesis was enhanced by some of these neuraminic acid derivatives when they were added to a culture of murine spleen lymphocytes, and the disaccharide nucleosides, 5-fluoro-2', 3'-isopropylidene-5'-O-(4-N-acetyl-2, 4-dideoxy-3, 6, 7, 8-tetra-O-acetyl-1-methoxycarbonyl-D-glycero-α-D-galactooctapyranosyl) uridine (compound 9) and 2', 3'-di-O-acetyl-4-N-acetyl-2, 4-dideoxy-3, 6, 7, 8-tetra-O-acetyl-1-methoxycarbonyl-D-glycero-α-D-galactooctapyranosyl) inosine (compound 10), were especially effective. The above disaccharide nucleosides and their starting materials, 5-fluoro-2', 3'-isopropylidene uridine (FIU) and 2', 3'-di-O-acetylinosine (DAI), suppressed in vitro primary antibody response toward sheep red blood cells (SRBC). In vivo antibody response toward SRBC was also suppressed when compound 9 or 10 was injected intraperitoneally into mice with SRBC. Moreover, lymphocytes incubated with compound 9 or 10 showed suppressor activity on primary anti-SRBC antibody response in vitro. On the other hand, FIU and DAI did not induce the suppressor activity of murine lymphocytes in vivo or in vitro. The induction of suppressor cells by compounds 9 and 10 was abolished by pretreatment of the lymphocytes with anti Thy-1 antiserum plus complement. These results suggest that these disaccharide nucleosides can induce suppressor T cells.

  我们研究了 N-乙酰神经氨酸的 α-和 β-甲基糖苷及其二糖衍生物对小鼠淋巴细胞增殖和免疫功能的影响。在小鼠脾脏淋巴细胞培养液中加入其中一些神经氨酸衍生物后，Con A 诱导的脱氧核糖核酸（DNA）合成增加得到了增强，而双糖核苷、5-氟-2'，3'-异亚丙基-5'-O-（4-N-乙酰基-2，4-二脱氧-3、6，7，8-四-O-乙酰基-1-甲氧基羰基-D-甘油-α-D-半乳吡喃糖基）尿苷（化合物 9）和 2'，3'-二-O-乙酰基-4-N-乙酰基-2，4-二脱氧-3，6，7，8-四-O-乙酰基-1-甲氧基羰基-D-甘油-α-D-半乳吡喃糖基）肌苷（化合物 10）特别有效。上述双糖核苷及其起始原料--5-氟-2', 3'-异亚丙基尿苷（FIU）和 2',3'-二-O-乙酰基肌苷（DAI）--抑制了体外对绵羊红细胞（SRBC）的初级抗体反应。将化合物 9 或 10 腹腔注射到带有 SRBC 的小鼠体内，也会抑制体内对 SRBC 的抗体反应。此外，用化合物 9 或 10 培养的淋巴细胞在体外对初级抗 SRBC 抗体反应表现出抑制活性。另一方面，FIU 和 DAI 在体内和体外均不能诱导小鼠淋巴细胞的抑制活性。用抗 Thy-1 抗血清加补体预处理淋巴细胞后，化合物 9 和 10 对抑制细胞的诱导作用就会消失。这些结果表明，这些双糖核苷可以诱导抑制性 T 细胞。
• Studies on Sialic Acids. Part XXVIII. Synthesis of Disaccharide Nucleoside Derivatives of 3-Deoxy-D-glycero-D-galacto-2-nonulosonic Acid (KDN).
  作者：Mitsunobu NAKAMURA、Shuji FUJITA、Haruo OGURA

  DOI：10.1248/cpb.41.21

  日期：——

  The reaction of benzyl 4, 5, 7, 8, 9-penta-O-acetyl-2-bromo- or -chloro-2, 3-dideoxy-D-glycero-β-D-galacto-2-nonulopyranosonate (2, 3) with uridine, 5-fluorouridine, and cytidine under Koenigs-Knorr reaction conditions gave the corresponding (2→5) linked disaccharide uncleoside derivatives, in yields of 32-47%. A similar reaction of 3 with inosine gave the (2→N1) linked derivative. These uncleoside analogues were converted into the final target compounds.The configuration at the anomeric position of these compounds was elucidated by means of proton and carbon unclear magnetic resonance (1H-, 13C-NMR)analysis, and consideration of the rate of hydrolysis of the (2→5) glycosidic linkage.

  在柯尼希斯-克诺尔反应条件下，4、5、7、8、9-五-O-乙酰基-2-溴或-氯-2，3-二脱氧-D-甘油-β-D-半乳糖-2-壬磺吡喃糖酸苄基酯（2，3）与尿苷、5-氟尿苷和胞苷反应，得到相应的（2→5）连接二糖叔叔苷衍生物，产率为 32-47%。将 3 与肌苷进行类似反应，可得到（2→N1）连接的衍生物。通过质子和碳不清晰磁共振（1H-, 13C-NMR）分析以及考虑（2→5）糖苷键的水解速度，阐明了这些化合物在异构体位置上的构型。
• Process for producing nucleoside derivatives
  申请人：Sumitomo Chemical Company, Limited

  公开号：EP0894868A2

  公开（公告）日：1999-02-03

  There is disclosed a process for producing a nucleoside derivative of the formula [I]: characterized by contacting 2',3',5'-O-triacylribonucleoside derivative of the formula [II]: with an ester hydrolase: (i) capable of regio-selectively deacylating the acyl group at 5'-O-position in the formula [II] above, and (ii) having an amino acid sequence encoded by a gene which hybridizes to a nucleotide sequence encoding an amino acid sequence of SEQ ID NO: 1

  本发明公开了一种生产式[I]核苷衍生物的工艺： 其特征在于将式[II]的2',3',5'-O-三酰基核苷衍生物 与酯水解酶接触： (i) 能够对上述式[II]中 5'-O-位上的酰基进行选择性脱酰基，和 (ii) 具有与编码 SEQ ID NO: 1 氨基酸序列的核苷酸序列杂交的基因所编码的 氨基酸序列