2',3'-Di-O-acetyl-5'-deoxy-5'-(methylthio)adenosine | 119771-17-4

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 2',3'-Di-O-acetyl-5'-deoxy-5'-(methylthio)adenosine
• 英文别名: 2',3'-Di-O-acetyl-5'-S-methyl-5'-thioadenosine；[(2S,3S,4R,5R)-4-acetyloxy-5-(6-aminopurin-9-yl)-2-(methylsulfanylmethyl)oxolan-3-yl] acetate
• CAS: 119771-17-4
• 化学式: C₁₅H₁₉N₅O₅S
• 分子量: 381.412
• InChiKey: DXQNSDOONUEPIA-SDBHATRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  157
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2',3'-Di-O-acetyl-5'-deoxy-5'-(methylthio)adenosine 在 三氯化锑 吡啶 、 (diethylamido)sulfur trifluoride 、 氨 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 19.5h， 生成 2',3'-Di-O-acetyl-5'-O-methyl-5'-(methylthio)adenosine
  参考文献：
  名称：

  Nucleic Acid Related Compounds. 80. Synthesis of 5'-S-(Alkyl and aryl)-5'-fluoro-5'-thioadenosines with Xenon Difluoride or (Diethylamido)sulfur Trifluoride, Hydrolysis in Aqueous Buffer, and Inhibition of S-Adenosyl-L-homocysteine hydrolase by derived "Adenosine 5'-Aldehyde" Species

  摘要：

  Treatment of 5/-S-(alkyl and aryl)-5'-thioadenosine derivatives 2 with XeF2, or the corresponding sulfoxides 3 with DAST/SbCl3, gave diastereomeric 5'-fluoro compounds which were deprotected to give the 5'-S-(alkyl and aryl)-5'-fluoro-5'-thioadenosine analogues 5. Stereochemistry was established by X-ray crystallography, and F-19 NMR chemical shifts were definitive for configurationally-related 5'-fluoro diastereomers. Sulfoxidation and thermolysis afforded the fluoromethylene analogues with retained relative configuration. The nucleoside 5'-alpha-fluoro thioethers 5 underwent spontaneous hydrolysis in aqueous buffer to give derived ''adenosine 5'-aldehyde'' species which caused potent time-dependent inactivation of S-adenosyl-L-homocysteine hydrolase.

  DOI：

  10.1021/jo00082a010
• 作为产物：
  描述：

  (2R,3R,4S,5S)-2-(6-氨基嘌呤-9-基)-5-(甲基亚磺酰甲基)四氢呋喃-3,4-二醇 在 4-二甲氨基吡啶 、 二甲氨基三氟化硫 、 氨 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 7.0h， 生成 2',3'-Di-O-acetyl-5'-deoxy-5'-(methylthio)adenosine
  参考文献：
  名称：

  5'-脱氧-5'-（甲硫基）腺苷的新型5'-氟化类似物的合成和抗增殖作用。

  摘要：

  5'-脱氧-5'-[（单氟甲基）硫代]腺苷（9）和5'-脱氧-5'-氟-5'-（甲硫基）腺苷（10），这是5'-脱氧-5的两个新类似物已经合成了'-（甲硫基）腺苷（MTA）并评估了它们对MTA磷酸化酶的底物和抑制活性，以及​​它们在L1210（MTA磷酸化酶缺陷）和L5178Y（含MTA磷酸化酶）鼠白血病细胞系中的生物学作用。化合物9是一种有效的MTA磷酸化酶竞争性抑制剂，Ki值为3.3 microM，并且还是一种底物，其活性约为MTA的53％。化合物10对磷酸化酶的抑制作用明显较小，Ki值为141 microM。其底物活性的缺乏归因于快速的非酶降解。在L1210和L5178Y细胞中，9的50％生长抑制浓度（48 h）分别为300和200 microM。对于10，这些各自的值为2和0.7 microM。这些系统中9的初始特征表明，它与MTA的不同之处在于它不充当多胺生物合成途径的产物调节剂。

  DOI：

  10.1021/jm00125a012

文献信息

• [EN] PHARMACEUTICAL AGENTS, COMPOSITIONS, AND METHODS RELATING THERETO<br/>[FR] AGENTS PHARMACEUTIQUES, COMPOSITIONS ET PROCÉDÉS ASSOCIÉS
  申请人：ALLTECH INC

  公开号：WO2018212980A1

  公开（公告）日：2018-11-22

  The present disclosure provides compounds of formulas (l)-(3), and compositions and methods of use thereof. The present disclosure also provides methods of preparing a provided compound and composition, and methods of characterizing a provided compound and composition.

  本公开提供了以下化合物的结构式(l)-(3)，以及它们的组合物和使用方法。本公开还提供了制备所述化合物和组合物的方法，以及表征所述化合物和组合物的方法。
• Synthesis of fluorinated derivatives of methionine and 5′-deoxy-5′-(methylthio)-adenosine using the mccarthy transformation of sulfoxides to α-fluoro thioethers
  作者：Janice R. Sufrin、Arthur J. Spiess、Vitauts Alks

  DOI：10.1016/s0022-1139(00)80377-2

  日期：1990.8

  trifluoride (DAST) or dimethylaminosulfur trifluoride (meDAST) yielded N-acetyl-S-(monofluoromethyl)homocysteine methyl ester as the sole fluorinated product. In contrast, treatment of 2′,3′-di-O-acetyl-5′-(methylthio)adenosine sulfoxide with DAST or meDAST unexpectedly produced three novel fluorinated products.

  用二乙基氨基三氟化硫（DAST）或二甲基氨基三氟化硫（meDAST）处理N-乙酰甲硫氨酸亚砜甲酯，得到的N-乙酰基-S-（单氟甲基）高半胱氨酸甲酯是唯一的氟化产物。相反，用DAST或meDAST处理2'，3'-二-O-乙酰基-5'-（甲硫基）腺苷亚砜意外地产生了三种新颖的氟化产物。
• Fluorination of 5′-deoxy-5′-(methylthio)adenosine with xenon difluoride provides an expedient synthesis of (fluoromethylthio)adenosine
  作者：Georges Guillerm、Marie Gâtel

  DOI：10.1039/p19940000153

  日期：——

  Fluorination of 5′-deoxy-5′-(fluoromethylthio)adenosine derivatives with xenon difluoride at –60 °C in dichloromethane occurs exclusively at the methylthio position to provide a simple and efficient preparation of 5′-deoxy-5′-(fluoromethylthio)adenosine.

  在–60°C的二氯甲烷中，氟化二氟氙对5'-脱氧-5'-（氟甲硫基）腺苷衍生物的氟化仅在甲硫基位置发生，以提供简单有效的5'-脱氧-5'-（氟甲硫基）制备方法腺苷。
• Antitrypanosomal activity of purine nucleosides can be enhanced by their conversion to O-acetylated derivatives
  作者：J R Sufrin、D Rattendi、A J Spiess、S Lane、C J Marasco、C J Bacchi

  DOI：10.1128/aac.40.11.2567

  日期：1996.11

  Fifteen purine nucleosides and their O-acetylated ester derivatives were examined for in vitro antitrypanosomal activity against the LAB 110 EATRO isolate of Trypanosoma brucei brucei and two clinical isolates of Trypanosoma brucei rhodesiense. Initial comparisons of activity were made for the LAB 110 EATRO isolate. Three nucleoside analogs exhibited no significant activity (50% inhibitory concentrations [IC50s] of > 100 microM), whether they were O acetylated or unacetylated; three nucleosides showed almost equal activity (IC50s of < 5 microM) for the parent compound and the O-acetylated derivative; nine nucleosides showed significantly improved activity (> or = 3-fold) upon O acetylation; of these nine analogs, six displayed activity at least 10-fold greater than that of their parent nucleosides. The most significant results were those for four apparently inactive compounds which, upon O acetylation, displayed IC50s of < or = 25 microM. When the series of compounds was tested against T. brucei rhodesiense isolates (KETRI 243 and KETRI 269), their antitrypanosomal effects were comparable to those observed for the EATRO 110 strain. Thus, our studies of purine nucleosides have determined that O acetylation consistently improved their in vitro antitrypanosomal activity. This observed phenomenon was independent of their cellular enzyme targets (i.e., S-adenosylmethionine, polyamine, or purine salvage pathways). On the basis of our results, the routine preparation of O-acetylated purine nucleosides for in vitro screening of antitrypanosomal activity is recommended, since O acetylation transformed several inactive nucleosides into compounds with significant activity, presumably by improving uptake characteristics. O-acetylated purine nucleosides may offer in vivo therapeutic advantages compared with their parent nucleosides, and this possibility should be considered in future evaluations of this structural class of trypanocides.

  本研究对15种嘌呤核苷及其O-乙酰化酯衍生物在体外抗非洲锥虫病活性方面进行了研究，包括LAB 110 EATRO亚型的Trypanosoma brucei brucei和两种Trypanosoma brucei rhodesiense的临床分离株。首先比较了LAB 110 EATRO亚型的活性。其中三种核苷类似物没有显著活性（50%抑制浓度[IC50]大于100微米），无论它们是否被乙酰化；三种核苷显示出几乎相等的活性（IC50小于5微米）的母化合物和O-乙酰化衍生物；九种核苷在O-乙酰化后显示出显著改善的活性（大于或等于3倍）；在这九种类似物中，有六种显示出至少比其母核苷高10倍的活性。最显着的结果是四个表面上无活性的化合物，在O-乙酰化后显示出IC50小于或等于25微米的活性。当这一系列化合物对T. brucei rhodesiense分离物（KETRI 243和KETRI 269）进行测试时，它们的抗非洲锥虫病效果与EATRO 110株观察到的相当。因此，我们对嘌呤核苷的研究确定了O-乙酰化一直改善它们的体外抗非洲锥虫病活性。这种观察到的现象与它们的细胞酶靶点（即S-腺苷甲硫氨酸、多胺或嘌呤拯救途径）无关。基于我们的结果，建议常规制备O-乙酰化嘌呤核苷进行体外筛选抗非洲锥虫病活性，因为O-乙酰化将几种无活性的核苷转化为具有显著活性的化合物，可能通过改善摄取特性。与其母核苷比较，O-乙酰化嘌呤核苷在体内治疗上可能具有优势，这一可能性应在对这种结构类的锥虫药物进行未来评估时予以考虑。
• Nucleic acid related compounds. 79. Efficient conversions of thioethers to .alpha.-fluoro thioethers with DAST or DAST/antimony(III) chloride
  作者：Morris J. Robins、Stanislaw F. Wnuk

  DOI：10.1021/jo00067a009

  日期：1993.7

  Dialkyl or alkyl aryl thioethers, including nucleoside thioethers, undergo virtually quantitative conversion to alpha-fluoro thioethers with (diethylamino)sulfur trifluoride (DAST) in dichloromethane at ambient temperature. Antimony(III) chloride catalyzes the process.