L-cytidine | 65-46-3

• 物质功能分类: 生物化工 - 核苷类药物 - 核苷酸及其类似物
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: L-cytidine
• 英文别名: β-D-cytidine；β-L-cytidine；cytidine；4-amino-1-β-L-ribofuranosyl-1H-pyrimidin-2-one；1-β-L-Ribofuranosylcytosine；4-Amino-1-((2S,3S,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one；4-amino-1-[(2S,3S,4R,5S)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
• CAS: 65-46-3
• 化学式: C₉H₁₃N₃O₅
• 分子量: 243.219
• InChiKey: UHDGCWIWMRVCDJ-PSQAKQOGSA-N

物化性质

• 熔点：
  210-220 °C (dec.) (lit.)
• 比旋光度：
  31.5 º (c=0.6, H2O 25 ºC)
• 沸点：
  386.09°C (rough estimate)
• 密度：
  1.3686 (rough estimate)
• 溶解度：
  H2O:50 mg/mL
• 最大波长(λmax)：
  280 (pH 1)；229.5，271 (pH 7)
• LogP：
  -1.808 (est)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  129
• 氢给体数：
  4
• 氢受体数：
  5

安全信息

• TSCA：
  Yes
• 安全说明：
  S24/25
• 危险类别码：
  R68
• WGK Germany：
  3
• 海关编码：
  2934999090
• 危险品运输编号：
  NONH for all modes of transport
• RTECS号：
  UW7370000
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

胞苷简介

胞苷即胞嘧啶核苷，是组成核酸的一种核糖核苷（含有嘧啶碱基胞嘧啶），并构成遗传密码的一个单位。胞苷在脱氧核糖核酸和胞核糖核酸中与相应的鸟嘌呤以非共价形式配对。

用途

胞苷作为嘧啶核苷，主要用于生产抗肿瘤、抗病毒药物的中间体，是制造阿糖胞苷（Ara-C）、环胞苷（CycloC）、三磷酸胞苷（CTP）、胞二磷胆碱（CDP-Choline）等药物的主要原料。

制备

一种胞嘧啶核苷的制备方法包括以下步骤：

1. 硅烷化：将胞嘧啶和叔丁基二甲基氯硅烷经硅烷化反应得N-(叔丁基二甲基硅基)-2-(叔丁基二甲基硅氧基)-4-嘧啶胺，将该物质在三氯甲烷中溶解得到N-(叔丁基二甲基硅基)-2-(叔丁基二甲基硅氧基)-4-嘧啶胺的三氯甲烷溶液。

2. 糖苷合成：将四乙酰核糖在三氯甲烷中溶解后加入四氯化钛溶液，在18℃～30℃环境下滴加N-(叔丁基二甲基硅基)-2-(叔丁基二甲基硅氧基)-4-嘧啶胺的三氯甲烷溶液，经糖苷反应得胞嘧啶乙酰核糖。

3. 氨解：在18℃～30℃环境下向胞嘧啶乙酰核糖中加入氨的质量百分浓度为10%的氨的甲醇溶液（即甲醇氨溶液），经氨解反应得胞嘧啶核苷粗品。

4. 精制：将胞嘧啶核苷粗品加入乙醇中，在搅拌下加热回流溶解后加水，冷却至0℃±2℃析晶至少5小时后分离出固体，干燥，得到胞嘧啶核苷。

具体合成路线如下：

白色结晶性粉末、熔点：210℃～217℃

用途

胞苷用作药品合成原料和生化试剂。用于CTP、CDP-胆碱、2′、3′-二去氧胞苷、阿糖胞苷等的制备。

用途

胞苷还用于制造阿糖胞苷、环胞苷、CTP、胞二磷胆碱等。

反应信息

• 作为反应物：
  描述：

  L-cytidine 在 咪唑 、 4-二甲氨基吡啶 作用下， 以 吡啶 、 甲醇 为溶剂， 生成 6-N-((di-n-butylamino)-methylene)-2'-O-tert-butyldimethylsilyl-5'-O-(4,4'-dimethoxytrityl)-L-cytidine
  参考文献：
  名称：

  Synthesis and Enzymatic Digestion of an RNA Nonamer in Both Enantiomeric Forms

  摘要：

  The D- and L-RNA nonamers of the sequence r(GCUUCGGC)T have been synthesised for X-ray crystallographic purposes. In vitro digestion of the unnatural optical antipode by snake venom phosphodiesterase I takes place at an approximately 1800-fold slower rate than that of the natural D-nonamer. The digestion experiments showed-to our knowledge for the first time-that L-RNA can indeed be cleaved enzymatically when phosphodiesterase I from snake venom is used-as opposed to a number of cellular ribonucleases-which sheds an interesting light on the evolution and possibly structure/function relationship of venom versus cellular degradation enzymes. The broad substrate specificity of this enzyme could be taken advantage of to study and further optimise the resistance towards biodegradation of therapeutic L-RNA aptamers. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(00)00046-6
• 作为产物：
  描述：

  1-O-acetyl-2,3,4-tri-O-benzoyl-L-ribofuranose 在 苯磺酰胺 、 ammonium hydroxide 、 三氟甲磺酸三甲基硅酯 作用下， 以 吡啶 、 1,2-二氯乙烷 为溶剂， 反应 28.0h， 生成 L-cytidine
  参考文献：
  名称：

  Chirally-Modifiedoligonucleotides and the Control of Gene Expression. The Case of L-DNAS And-RNAS

  摘要：

  The affinity of L-DNAs, L-RNAs and L/D-DNAs for homopurine.homopyrimidine d.s. D-DNA and s.s. D-RNA was probed by gel electrophoresis and CD spectroscopy. It was found that the L-modified oligomers do not bind to d.s. DNA and to natural RNA that contains all four natural bases. Thus they cannot be used, in general, for the control of gene expression according to the antigene and antisense methodologies. Heterochiral complexes with 1:1 stoichiometry and low thermal stability are formed, instead, by homopurinic L-RNA or L/D-DNA and homopyrimidinic L-RNA with the W/C complementary natural RNA sequences.

  DOI：

  10.1080/07328319808004239

文献信息

• Macrocyclic compounds as inhibitors of viral replication
  申请人：Blatt M. Lawrence

  公开号：US20050267018A1

  公开（公告）日：2005-12-01

  The embodiments provide compounds of the general formulas I-XIX, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating flaviviral infection, including hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

  该实施例提供了一般式I-XIX的化合物，以及包括药物组合在内的组合物，其中包括一种主体化合物。该实施例还提供了治疗方法，包括治疗黄病毒感染的方法，包括丙型肝炎病毒感染的方法和治疗肝纤维化的方法，这些方法通常涉及向需要的个体施用一种主体化合物或组合物的有效量。
• [EN] N4-HYDROXYCYTIDINE AND DERIVATIVES AND ANTI-VIRAL USES RELATED THERETO<br/>[FR] N4-HYDROXYCYTIDINE, SES DÉRIVÉS ET UTILISATIONS ANTI-VIRALES
  申请人：UNIV EMORY

  公开号：WO2016106050A1

  公开（公告）日：2016-06-30

  This disclosure relates to N4-hydroxycytidine derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to the treatment and prophylaxis of viral infections.

  这项披露涉及N4-羟基胞嘧啶衍生物、组合物以及相关方法。在某些实施方式中，该披露涉及治疗和预防病毒感染。
• L-ribonucleosides from L-xylose
  作者：E Moyroud

  DOI：10.1016/s0040-4020(98)01119-3

  日期：1999.1.29

  L-Xylose was converted into a L-ribose derivative via an oxidation/reduction procedure. The L-ribosyl donor was submitted to a glycosidation reaction according to Vorbrüggen's conditions to give L-ribonucleosides (L-uridine, L-cytidine, L-adenosine and L-guanosine) in high yield.

  通过氧化/还原程序将L-木糖转化为L-核糖衍生物。根据Vorbrüggen的条件，使L-核糖基供体进行糖苷化反应，以高产率得到L-核糖核苷（L-尿苷，L-胞苷，L-腺苷和L-鸟苷）。
• Quasi-enantiomeric single-nucleoside and quasi-racemic two-nucleoside hydrochloride salts and ruthenium complexes of cytidine and 2′,3′-dideoxycytidine analogs unveiling the negligible structure-driving role of the 2′,3′-moieties
  作者：Felipe Terra Martins、Rodrigo S. Corrêa、Alzir Azevedo Batista、Javier Ellena

  DOI：10.1039/c4ce00678j

  日期：——

  In addition, the first examples of ruthenium(II) coordination complexes with cytidine nucleosides are reported here. The trans-bis-(triphenylphosphine)(lamivudinate)(2,2′-bipyridine)ruthenium(II) perchlorate and trans-bis-(triphenylphosphine)(cytidinate)(2,2′-bipyridine)ruthenium(II) perchlorate complexes have the same coordination geometry and similar chains made up of complex units intercalated

  晶体工程研究已经获得了对核苷分子组织的结构基础的见解。在这里，我们研究了五元环的3'-位置差异在准对映体胞苷基核苷分子构象和晶体堆积测定中的作用。首先，制备了与拉米夫定（2'，3'-二脱氧-3'-噻吩啶）盐酸盐同构的扎西他滨（2'，3'-二脱氧胞苷）盐酸盐。R 1 2（6）基序负责核苷和抗衡离子之间的配对，以及带有2 1的链和片的组装在两种盐中均观察到了与螺杆对称性相关的离子对，即使拉米夫定与扎西他滨在其C1'和C4'碳的相反手性方面也不相同，并且在3'-位的硫原子而不是亚甲基也是如此。基于盐酸扎西他滨与拉米夫定盐酸盐之间的同构性，但晶体结构为准对映异构体，本研究设计了具有两个核苷单晶形式的盐酸盐。所获得的杂化结构是准外消旋体，其中与R 1 2（6）成对的拉米夫定和氯化物组装的链可以通过拟反演对称性与扎西他滨和氯化物相关，但具有相反的生长方向。此外，钌的第一个例子（II）与胞苷核苷的配位复
• A cross-chiral RNA polymerase ribozyme
  作者：Jonathan T. Sczepanski、Gerald F. Joyce

  DOI：10.1038/nature13900

  日期：2014.11.20

  Here, a cross-chiral RNA polymerase is developed—an RNA enzyme that can catalyse the templated polymerization of activated mononucleotides that are of the opposite handedness—shedding light on how RNA-based life could have emerged. It is widely assumed that homochirality is a requirement for life and that biological macromolecules must be of the same stereochemical 'handedness' to interact efficiently. Working with Leslie Orgel and others, Gerald Joyce extended this idea in 1984 to suggest that homochirality may also be essential for the origins of life, as templated polymerization of RNA occurs readily in a homochiral system but is impaired in racemic mixtures. Now Joyce and co-author Jonathan Sczepanski show that RNAs of opposing chirality can work together. They devised a D-RNA enzyme that catalyses the polymerization of L-RNA on a L-RNA template — and vice versa. The catalytic potency of this ribozyme is sufficient for it to synthesize its own enantiomer by joining 11 component oligonucleotides. The ribozyme is thought to interact with its substrates via tertiary contacts rather than Watson–Crick base pairing. This unexpected finding will add a new dimension to thoughts on how life could have emerged in an 'RNA world'. Thirty years ago it was shown that the non-enzymatic, template-directed polymerization of activated mononucleotides proceeds readily in a homochiral system, but is severely inhibited by the presence of the opposing enantiomer1. This finding poses a severe challenge for the spontaneous emergence of RNA-based life, and has led to the suggestion that either RNA was preceded by some other genetic polymer that is not subject to chiral inhibition2 or chiral symmetry was broken through chemical processes before the origin of RNA-based life3,4. Once an RNA enzyme arose that could catalyse the polymerization of RNA, it would have been possible to distinguish among the two enantiomers, enabling RNA replication and RNA-based evolution to occur. It is commonly thought that the earliest RNA polymerase and its substrates would have been of the same handedness, but this is not necessarily the case. Replicating d- and l-RNA molecules may have emerged together, based on the ability of structured RNAs of one handedness to catalyse the templated polymerization of activated mononucleotides of the opposite handedness. Here we develop such a cross-chiral RNA polymerase, using in vitro evolution starting from a population of random-sequence RNAs. The d-RNA enzyme, consisting of 83 nucleotides, catalyses the joining of l-mono- or oligonucleotide substrates on a complementary l-RNA template, and similar behaviour occurs for the l-enzyme with d-substrates and a d-template. Chiral inhibition is avoided because the 106-fold rate acceleration of the enzyme only pertains to cross-chiral substrates. The enzyme’s activity is sufficient to generate full-length copies of its enantiomer through the templated joining of 11 component oligonucleotides.

  这里研制了一种交叉手性的RNA聚合酶（一种能够催化与自身手性相反的活化单核苷酸模板聚合的RNA酶），为基于RNA的生命如何起源提供了启示。普遍认为手性均一是生命的要求，生物大分子必须具有一样的立体化学"手性"才能有效相互作用。与 Leslie Orgel 等人一起，Gerald Joyce于1984年提出手性均一对于生命起源可能同样是必不可少，因为在手性均一系统中RNA的模板聚合反应能顺畅进行，而外消旋混合物中反应会受阻。现在Joyce和合作者Jonathan Sczepanski表明手性相反的RNAs可以在一起工作。他们设计出一种能够催化L-RNA在L-RNA模板上聚合的D-RNA酶，反之亦然。这种核酶的催化效率足以通过连接11个寡核苷酸组份来合成其对映体。人们认为这种核酶与底物间的相互作用是通过三级结构接触而非Watson-Crick碱基配对实现的。这一发现会为"RNA世界"中的生命如何起源开启新的思路。30年前就已经表明，非酶催化的模板调控活化单核苷酸聚合反应在手性均一系统中进行顺畅，但会严重抑制于相反手性的存在。这一发现使得RNA为基础的生命如何自发产生成为一个难题，由此带来RNA可能之前存在某种不受手性抑制的其他遗传聚合物，或是基于RNA的生命之前存在化学过程打破手性对称性两种猜想。一旦产生了一种能催化RNA聚合的RNA酶，就有可能分辨两种对映体，从而发生RNA复制和基于RNA的进化。普遍认为最原始的RNA聚合酶及底物手性一致，但不一定是这种情形。复制D手性及L手性的RNA分子可能会同时出现，基于一种手性的RNA结构可以催化相反手性的活化单核苷酸的模板聚合。这里我们用随机序列RNA群体为起始的体外进化研发出这样一种交叉手性的RNA聚合酶。由83个核苷酸组成的D-RNA酶催化L手性单核苷酸或寡核苷酸底物在互补的L手性模板上聚合，反之对L-酶及D-底物和D-模板也成立。因为这种酶的106倍的速率加速只对应于交叉手性底物，从而避开了手性抑制。这种酶活性足以通过模板调控连接11个寡核苷酸产生出其对映体的全长拷贝。