5-O-tert-butyldimethylsilyl-1,N-dehydro-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-ribitol | 153172-33-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-O-tert-butyldimethylsilyl-1,N-dehydro-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-ribitol
• 英文别名: (3aR,4R,6aS)-4-(((tert-butyldimethylsilyl)oxy)methyl)-2,2-dimethyl-4,6a-dihydro-3aH-[1,3]dioxolo[4,5-c]pyrrole；[(3aR,4R,6aS)-2,2-dimethyl-4,6a-dihydro-3aH-[1,3]dioxolo[4,5-c]pyrrol-4-yl]methoxy-tert-butyl-dimethylsilane
• CAS: 153172-33-9
• 化学式: C₁₄H₂₇NO₃Si
• 分子量: 285.459
• InChiKey: CJMAHNQXMYIPQQ-GRYCIOLGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.98
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  40
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-O-tert-butyldimethylsilyl-1,N-dehydro-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-ribitol 在 palladium diacetate 、 正丁基锂 作用下， 以 六甲基磷酰三胺 为溶剂， 反应 3.0h， 生成 苯甲腈,4-[(3aS,4S,6R,6aR)-6-[[[(1,1-二甲基乙基)二甲基甲硅烷基]氧代]甲基]四氢-2,2-二甲基-4H-1,3-二噁唑并[4,5-c]吡咯-4-基]-
  参考文献：
  名称：

  Transition state analogue inhibitors of protozoan nucleoside hydrolases

  摘要：

  Protozoan parasites are unable to synthesize purines de novo and must rely on purine salvage pathways for their requirements. Nucleoside hydrolases, which are not found in mammals, function as key enzymes in purine salvage in protozoa. Inhibition of these enzymes may disrupt purine supply and specific inhibitors are potential therapeutic agents for the control of protozoan infections. A series of 1,4-dideoxy-1,4-imino-D-ribitols bearing C-bonded aromatic substituents at C-1 have been synthesized, following carbanion additions to the imine 2, and tested as potential nucleoside hydrolase inhibitors. Nucleoside analogues 8, 11, 14, 17, 20, 24-26, 28 exhibit K-i values in the range 0.2-22 mu M against two representative isozymes of protozoan nucleoside hydrolases. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00210-2
• 作为产物：
  描述：

  2,3-O-异亚丙基-D-核糖酸 gamma-内酯 在 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 N-氯代丁二酰亚胺 、 palladium on activated charcoal 、 氢气 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， -15.0~70.0 ℃ 、551.59 kPa 条件下， 反应 123.5h， 生成 5-O-tert-butyldimethylsilyl-1,N-dehydro-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-ribitol
  参考文献：
  名称：

  [EN] COMPOSITIONS AND METHODS FOR INHIBITING VIRAL POLYMERASE
  [FR] COMPOSITIONS ET PROCÉDÉS D'INHIBITION D'UNE POLYMÉRASE VIRALE

  摘要：

  本文描述的是Formula (I)的化合物。Formula (I)的化合物在抑制病毒RNA聚合酶活性和病毒复制的方法中很有用。还提供了包含Formula (I)化合物的药物组合物，以及使用Formula (I)化合物治疗病毒感染的方法。

  公开号：

  WO2013158746A1

文献信息

• Addition of Lithiated 9-Deazapurine Derivatives to a Carbohydrate Cyclic Imine:  Convergent Synthesis of the Aza-<i>C</i>-nucleoside Immucillins
  作者：Gary B. Evans、Richard H. Furneaux、Tracy L. Hutchison、Hollis S. Kezar、Philip E. Morris,、Vern L. Schramm、Peter C. Tyler

  DOI：10.1021/jo0155613

  日期：2001.8.1

  Means have been developed for the synthesis and addition of 9-deaza-9-lithiopurine derivatives to the carbohydrate-derived cyclic imine 6 in facile convergent syntheses of biologically active aza-C-nucleosides.

  已经开发了在生物活性氮杂-C-核苷的容易会聚合成中将9-脱氮基-9-硫代嘌呤衍生物合成和添加至碳水化合物衍生的环亚胺6的方法。
• Process for preparing 2-pyrrolidinyl-1H-pyrrolo&lsqb;3,2-d&rsqb;pyrimidine inhibitors of nucleoside metabolism
  申请人：Industrial Research Limited

  公开号：US06693193B1

  公开（公告）日：2004-02-17

  A process of preparing a compound of the formula (I) wherein B is chosen from OH, NH2, NHR, H or halogen; D is chosen from OH, NH2, NHR, H halogen or SCH3; R is an optionally substituted alkyl, aralkyl or aryl group; and Z is selected from OH, hydrogen, halogen, hydroxy, SQ or OQ, Q is an optionally substituted all, aralkyl or aryl group; or a tautomer thereof; or a pharmaceutically acceptable salt thereof; or an ester thereof; or a prodrug thereof, which comprises reacting a compound of the formula (II)  with an anion produced by abstraction of the bromine or iodine atom from a compound of formula (XIX),  to form a compound of formula (XX) The compound of formula (XX) is N- and O-deprotected to obtain the compound of formula (I).

  将公式（I）的化合物制备过程翻译成中文： 其中B选择自OH、NH2、NHR、H或卤素；D选择自OH、NH2、NHR、H、卤素或SCH3；R是可选择取代的烷基、芳基烷基或芳基；Z选择自OH、氢、卤素、羟基、SQ或OQ，Q是可选择取代的烷基、芳基烷基或芳基；或其互变异构体；或其药学上可接受的盐；或其酯；或其前药，包括将公式（II）的化合物与通过从公式（XIX）的化合物中提取溴或碘原子而产生的负离子反应，形成公式（XX）的化合物。公式（XX）的化合物经N-和O去保护得到公式（I）的化合物。
• Exploring Structure−Activity Relationships of Transition State Analogues of Human Purine Nucleoside Phosphorylase
  作者：Gary B. Evans、Richard H. Furneaux、Andrzej Lewandowicz、Vern L. Schramm、Peter C. Tyler

  DOI：10.1021/jm030145r

  日期：2003.7.1

  transition state analogue inhibitors of purine nucleoside phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2'-, 3'-, or 5'-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazapurine, as well as methylene-bridged analogues, have been synthesized and tested for their inhibition of human purine nucleoside phosphorylase. All

  氮杂-C-核苷Immucillin-H和Immucillin-G是嘌呤核苷磷酸化酶的过渡态类似物抑制剂，嘌呤核苷磷酸化酶是控制T细胞增殖的治疗靶标。已合成在氮杂嘌呤部分的2'-，3'-或5'-位或在脱氮嘌呤的6-，7-或8-位修饰的Immucillin类似物以及亚甲基桥连的类似物。并测试了它们对人嘌呤核苷磷酸化酶的抑制作用。所有类似物都是较弱的抑制剂，这反映了母体imimcillins对过渡状态特征的更好捕获。
• Imino-<i>C</i>-nucleoside Synthesis:  Heteroaryl Lithium Carbanion Additions to a Carbohydrate Cyclic Imine and Nitrone
  作者：Gary B. Evans、Richard H. Furneaux、Herwig Hausler、Janus S. Larsen、Peter C. Tyler

  DOI：10.1021/jo035744k

  日期：2004.3.1

  Promotion by Lewis acid of the addition of some aryllithiums to a carbohydrate-based imine, which has allowed a more facile synthesis of some imino-C-nucleoside analogues, is described. Use of the corresponding nitrone does not assist in some cases, but lithiated acetonitrile adds to it efficiently to give a product from which further C-nucleoside analogues can be derived.

  促进通过加入一些芳基锂的一种基于碳水化合物的亚胺，其中已经允许的一些亚氨基的更容易合成的路易斯酸Ç核苷类似物，进行说明。在某些情况下，使用相应的腈没有帮助，但是将锂化的乙腈有效地添加到其中，可以得到可以进一步衍生出C-核苷类似物的产物。
• Synthesis of transition state inhibitors for N-riboside hydrolases and transferases
  作者：Richard H Furneaux、Gerrit Limberg、Peter C Tyler、Vern L Schramm

  DOI：10.1016/s0040-4020(96)01172-6

  日期：1997.2

  A number of 1,4-dideoxy-1,4-imino-1-(S)-(substituted phenyl)-d-ribitols bearing aromatic OH, NH2, NO2, CO2H and halogeno moieties, and a 3-pyridyl analogue have been synthesized. The key step is the condensation of aryllithium or aryl Grignard reagents with the imine 3; derived from the protected 1,4-dideoxy-1,4-imino-d-ribitol 4.

  许多带有芳族OH，NH 2，NO 2，CO 2 H和卤素部分的1，4-二脱氧-1，4-亚氨基-1-（S）-（取代的苯基）-d-核糖醇，以及3-吡啶类似物已经合成。关键步骤是芳基锂或芳基格氏试剂与亚胺3的缩合。衍生自受保护的1,4-二脱氧-1,4-亚氨基-d-核糖醇4。