3'-mercapto-5'-O-DMT-3'-deoxythymidine | 123126-01-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 3'-mercapto-5'-O-DMT-3'-deoxythymidine
• 英文别名: DMT(-5)2-deoxy-D-eryPenf3SH(b)-thymin-1-yl；1-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-sulfanyloxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 123126-01-2
• 化学式: C₃₁H₃₂N₂O₆S
• 分子量: 560.671
• InChiKey: YEPBQOCNULTJPD-OZNIXHKMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  40
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  87.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3'-mercapto-5'-O-DMT-3'-deoxythymidine 在 triethylamine tris(hydrogen fluoride) 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 16.5h， 生成 1-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-((((2S,3S,5R)-3-hydroxy-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-yl)methyl)disulfaneyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  3'-5'和3'-6'二硫键连接的寡核苷酸的合成，动态组合化学和PCR扩增

  摘要：

  合成了通过3'-5'或3'-6'连接的二硫二胸苷，并通过磷酸三酯和亚磷酰胺固相寡核苷酸合成方法将其掺入寡核苷酸。在硫醇和寡核苷酸的存在下，二硫键被裂解并可逆地形成。在存在巯基乙醇的情况下，该链接显示出对指定模板的序列适应性。在聚合酶链反应（PCR）中，聚合酶可以耐受人工的3'-5'和3'-6'二硫键。通过使用测序分析，我们显示了单个突变经常在PCR的扩增产物中随机发生。

  DOI：

  10.1002/anie.201405761
• 作为产物：
  描述：

  2,3'-anhydro-5'-O-(4,4'-dimethoxytrityl)thymidine 在 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 3'-mercapto-5'-O-DMT-3'-deoxythymidine
  参考文献：
  名称：

  固相合成含有3'-S-硫代磷酸硫酯键的寡脱氧核苷酸。

  摘要：

  首次开发了一种完全自动化的程序，用于使用硫代磷酰胺基单体将3'-S-硫代磷酸硫酯键结合到DNA中。与活化剂5-乙基硫代四唑或4,5-二氰基咪唑中的任一种的偶联产率在80-90％的范围内。当在0.2或1摩尔反应柱上进行偶联时，偶联收率同样好，因此有利于大规模合成。

  DOI：

  10.1081/ncn-100002553

文献信息

• Reverse-direction (5′→3′) synthesis of oligonucleotides containing a 3′-S-phosphorothiolate linkage and 3′-terminal 3′-thionucleosides
  作者：James W. Gaynor、Michael M. Piperakis、Julie Fisher、Richard Cosstick

  DOI：10.1039/b923545k

  日期：——

  5′-oxygen to the 3′-thiol function. 5′→3′ Synthesis of oligonucleotides gave relatively poor yields for the internal incorporation of 3′-thionucleosides [to give a 3′-S-phosphorothiolate (3′-SP) linkage] and multiple 3′-SP modifications could not be introduced by this method. However, the reverse direction approach provided an efficient route to oligonucleotides terminating with a 3′-thionucleoside

  含3'- thionucleosides寡脱氧核苷酸的合成已使用反向方向（5'→3'）的方法探讨的基础上，其含有一个或三苯甲基二甲氧基三苯甲基保护的核苷单体3'-硫醇和一个5'- ø -亚磷酰胺。这些单体相对容易制备，因为基于三苯甲基的保护基优先于5'-羟基以3'-硫醇选择性引入。作为替代方法，可以诱导三苯甲基从5'-氧迁移至3'-硫醇功能。5'→3'的合成寡核苷酸的合成相对内部3'-thionucleosides [产生3'- S]的收率相对较低-硫代磷酸酯（3'-SP）键]和多个3'-SP修饰不能通过该方法引入。然而，反向方法提供了以3'-硫代核苷终止的寡核苷酸的有效途径。这些硫封端的低聚物的直接合成以前没有报道，并且所描述的方法适用于衍生自胸腺嘧啶，胞嘧啶和腺嘌呤的2'-脱氧-3'-硫核苷。
• Oligodeoxynucleotides containing 3′-allylether, 3′-allylsulfide and their saturated derivatives as phosphate mimics
  作者：Xiaodong Cao、Mark D. Matteucci

  DOI：10.1016/0040-4039(94)85210-3

  日期：1994.4

  thymidine-thymidine dimers containing 3′-allylether, 3′-allylsulfide connections and their saturated derivatives have been prepared and incorporated into oligodeoxynucleotides (ODNs). The 3′-allylether analog results in only a modest destablization of double helix formation with a complementary ssRNA relative to the phosphodiester linkage. This fact coupled with its facile synthesis may point to an application

  已经制备了一系列含有3'-烯丙基，3'-烯丙基硫键及其饱和衍生物的新型胸苷-胸苷二聚体，并将其掺入寡脱氧核苷酸（ODN）中。3'-烯丙基类似物仅导致相对于磷酸二酯键具有互补ssRNA的双螺旋形成的适度去稳定。这个事实及其容易的合成可能表明这种连接在基于寡核苷酸的治疗剂中的应用。
• A mild method for the syntheses of 3′-thioformacetal dinucleotides: The development of diphenylphosphinate as a glycosyl donor
  作者：Jiancun Zhang、Mark D. Matteucci

  DOI：10.1016/0040-4039(95)01809-v

  日期：1995.11

  A mild and efficient procedure for the syntheses of 3'-thioformacetal dinucleotides is presented. The glycosylation synthon agent, diphenylphosphinate formacetal was developed as the intermediate for the coupling reaction under mild basic conditions. This method is compatible with purine deoxyribosides, unprotected amino groups and acid labile functionalities.
• Dinucleoside Monophosphate Analogues Containing Disulfide Linkages
  作者：Emma M. Witch、Richard Cosstick

  DOI：10.1080/07328319708006228

  日期：1997.7

  Two dinucleoside monophosphate analogues containing disulfide linkages (1 and 2) have been prepared for incorporation into oligonucleotides. The modified oligomers will be tested for their potential as antisense agents.
• Synthesis and binding properties of pyrimidine oligodeoxynucleoside analogs containing neutral phosphodiester replacements: the formacetal and 3'-thioformacetal internucleoside linkages
  作者：Robert J. Jones、Kuei Ying Lin、John F. Milligan、Shalini Wadwani、Mark D. Matteucci

  DOI：10.1021/jo00063a014

  日期：1993.5

  The replacement of the phosphodiester linkage with neutral, achiral, nuclease resistant entities is desirable for the development of oligodeoxynucleotide (ODN) analogs as therapeutic agents in either the antisense or antigene modes. Described herein is the use of the formacetal and 3'-thioformacetal connections as phosphodiester backbone analogs. Pyrimidine dimer blocks containing these moieties were synthesized and incorporated into ODNs in an alternating array with phosphodiester bonds, such that the ODNs had seven acetal and seven phosphodiester linkages. The binding properties of the resulting chimeric ODNs to single-stranded (ss) RNA and double-stranded (ds) DNA were then determined. ssRNA binding properties were determined by thermal denaturation (Tm) analysis, and the 3'-thioformacetal ODN/ssRNA duplex showed a 5.5-degrees-C enhancement in Tm relative to the control phosphodiester ODN. The triple helix formation properties of the 3'-thioformacetal and formacetal ODNs were determined by footprint and restriction enzyme inhibition assays. The 3'-thioformacetal ODN binds to dsDNA with an affinity slightly less than the control ODN. The high affinity and specificity of an ODN containing the 3'-thioformacetal for the ssRNA target and dsDNA target suggest that this linkage is a promising analog for both antisense and triple helix therapeutic applications.