4-methylthiothymine | 55040-79-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 4-methylthiothymine
• 英文别名: 5-methyl-4-methylsulfanyl-1H-pyrimidin-2-one；5-Methyl-4-methylmercapto-1H-pyrimidin-2-on；5-methyl-6-methylsulfanyl-1H-pyrimidin-2-one
• CAS: 55040-79-4
• 化学式: C₆H₈N₂OS
• mdl: MFCD26792648
• 分子量: 156.208
• InChiKey: OWKFQGDPRUUKOJ-UHFFFAOYSA-N

物化性质

• 熔点：
  205-211 °C
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-methylthiothymine 在 硫酸氢铵 、 三氟甲磺酸三甲基硅酯 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.0h， 生成 1-(3-azido-2,3-dideoxy-α-D-erythro-pentofuranosyl)-5-methyl-4-methylthiopyrimidin-2(1H)-one
  参考文献：
  名称：

  FLT 和 AZT 4-甲硫基类似物的合成及其对 HIV 的评价

  摘要：

  甲硅烷基化的 4-甲基硫尿嘧啶和 4-甲基硫代胸腺嘧啶在 TMS 三氟甲磺酸酯存在下与甲基 2,3-双脱氧-3-氟-5-O-（4-苯基苯甲酰基）-D-赤型-戊呋喃糖苷（3）和甲基 3-缩合叠氮基-5-O-(叔丁基二苯基甲硅烷基)-2,3-双脱氧-D-赤型-五呋喃糖苷(8)，分别得到脱保护的相应核苷。3'-叠氮基核苷用三苯基膦还原成相应的 3'-氨基核苷。3'-氨基核苷也是通过 4-甲基硫代胸苷与 3-邻苯二甲酰亚胺糖 14 缩合然后脱保护获得的。AZT 的 4-甲硫基类似物 11 对 HIV 表现出中等活性。

  DOI：

  10.1002/ardp.19953280112
• 作为产物：
  描述：

  碘甲烷 、 alkaline earth salt of/the/ methylsulfuric acid 在 氢氧化钾 作用下， 生成 4-methylthiothymine
  参考文献：
  名称：

  Wheeler; McFarland, American Chemical Journal, 1910, vol. 43, p. 32

  摘要：

  DOI：

文献信息

• Synthesis and Antiviral Evaluation of Novel 2,3-Dihydroxypropyl Nucleosides from 2- and 4-Thiouracils
  作者：Adel A.-H. Abdel-Rahman、Abd-Allah SH. El-Etrawy、Ahmed E.-S. Abdel-Megied、Ibrahim F. Zeid、El Sayed H. El Ashry

  DOI：10.1080/15257770802086898

  日期：2008.11.13

  chloride (2) afforded 2-[[(2,2-Dimethyl-1,3-dioxolan-4-yl) methyl]thio]pyrimidin-4(1H)-ones 3a-c and 4-[[(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl]thio] pyrimidin-2(1H)-ones 8a,b, respectively. Further alkylation with 2 and/or 2,3-O-isopropylidine-1-O-(4-toluenesulfonyl)-glycerol (4) gave the acyclo N-nucleosides 5a-c and 9a,b whose deprotection afforded 6a-c and 10a,b. 2-(Methylthio)pyrimidin-4(1H)-ones 11a-c

  用2，3-O-异亚丙基-2，3-二羟丙基氯（2）对2-硫尿嘧啶1a-c和4-硫尿嘧啶7a，b进行区域选择性烷基化，得到2-[[（（2，2-二甲基-1,3-）二氧戊环-4-基）甲基]硫基]嘧啶-4（1H）-基3a-c和4-[[（（2,2-二甲基-1,3-二氧戊环-4-基）甲基]硫基]嘧啶-2 （1H）-分别为8a，b。用2和/或2,3-O-异丙基-1--1-O-（4-甲苯磺酰基）-甘油（4）进一步烷基化得到无环N-核苷5a-c和9a，b，它们的脱保护得到6a-c和10a ，b。将2-（甲硫基）嘧啶-4（1H）-酮11a-c和4-（甲硫基）嘧啶-2（1H）-酮14a，b用2和/或4处理得到12a-c和15a，b将它们去保护得到13a-c和16a，b。用两个当量的2处理嘧啶-2,4（1H，3H）-二硫酮17a-c，得到2,4-双[[（（2,2-二甲基-1,3-二氧杂戊-4-基）甲基]] [硫代]
• [EN] PHOSPHITYLATION PROCESS<br/>[FR] PROCEDE DE PHOSPHITYLATION
  申请人：AVECIA BIOTECHNOLOGY INC

  公开号：WO2004035599A1

  公开（公告）日：2004-04-29

  A process for the phosphitylation of an alcohol or thiol with a phosphitylation agent in the presence of an activator is provided. The activator has the formula (1): wherein p is 0 or an integer from 1 to 4 and R for each occurrence is a substituent. Preferably X7 is O and p is 0. The activator is commonly employed as a salt complex with an organic base. Preferred alcohols or thiols include nucleosides and oligonucleotides. The process is particularly suited for the synthesis of phosphoramidites.

  提供了一种在活化剂存在下，使用磷酰化试剂对醇或硫醇进行磷酰化的方法。活化剂具有公式（1）：其中p为0或1至4的整数，每次出现的R为取代基。最好X7为O，p为0。活化剂通常与有机碱形成盐络合物一起使用。首选的醇或硫醇包括核苷和寡核苷酸。该方法特别适用于磷酰胺酰胺的合成。
• Silylated oligonucleotide compounds
  申请人：Moody John David

  公开号：US20070004911A1

  公开（公告）日：2007-01-04

  Oligonucleotide comprising at least one internucleotide phosphorus atom protected with a group of formula —X a SiR 3 R 4 R 5 provided. X a represent 0 or S, and R 3 , R 4 and R 5 each independently are optionally substituted hydrocarbyl groups, selected such that that total number of carbon atoms in R 3 plus R 4 plus R 5 is 4 or more. Process for the preparation of these oligonucleotides, intermediate compounds useful therein, and process for the preparation of the intermediate compounds are also provided.

  提供至少包含一个以公式-XaSiR3R4R5保护的核苷酸，其中Xa代表0或S，而R3、R4和R5各自独立地是可选取的取代的烃基，选取的烃基总碳原子数为4或更多。还提供了制备这些寡核苷酸的过程、在其中有用的中间化合物以及制备中间化合物的过程。
• SYNTHESIS OF ARA-2'-O-METHYL-NUCLEOSIDES, CORRESPONDING PHOSPHORAMIDITES AND OLIGONUCLEOTIDES INCORPORATING NOVEL MODIFICATIONS FOR BIOLOGICAL APPLICATION IN THERAPEUCTICS, DIAGNOSTICS, G- TETRAD FORMING OLIGONUCLEOTIDES AND APTAMERS
  申请人：Srivastava Suresh C.

  公开号：US20120149888A1

  公开（公告）日：2012-06-14

  The present invention relates to synthesis, purification and methods to obtain high purity novel 2′-arabino-O-methyl nucleosides and the corresponding phosphoramidites of various arabinonucleoside bases and introduction of such units into defined sequence synthetic DNA and RNA. Various synthetic oligonucleotides, such as HIV integrase inhibitor 14-mer and thrombin binding oligonucleotide, thrombin-1, bearing ara-2′-omethyl modification have been synthesized. It is anticipated the oligonucleotides incorporating these monomers will exhibit biological activities related to antisense approach approach, design of better SiRNA's, diagnostic agents. Similarly, it is anticipated that oligonucleotides incorporating such novel nucleosides will be useful to develop therapeutic candidates designing stable G-quadruplexes and Aptamers for oligonucleotide structure, folding topology, evaluation of biochemical properties and design and develop as therapeutic agents. It is further anticipated that the nucleosides, phosphates and triphosphates of this invention could develop as therapeutic agents.

  本发明涉及合成、纯化和获取高纯度新型2'-阿拉伯核苷-O-甲基核苷和各种阿拉伯核苷基的相应磷酰胺酯的方法，并将这些单元引入到定义的序列合成DNA和RNA中。已合成了各种合成寡核苷酸，例如HIV整合酶抑制剂14-mer和凝血酶结合寡核苷酸，凝血酶-1，带有ara-2'-omethyl修饰。预计包含这些单体的寡核苷酸将展示与反义方法、更好的SiRNA设计、诊断剂相关的生物学活性。同样，预计包含这些新型核苷的寡核苷酸将有助于开发稳定的G四链体和寡核苷酸结构的Aptamers，用于寡核苷酸结构、折叠拓扑、生化特性的评估和设计和开发为治疗剂。进一步预计，本发明的核苷、磷酸盐和三磷酸盐可作为治疗剂开发。
• PROCESS FOR PREPARING PHOSPHATE COMPOUND BEARING ISOTOPE
  申请人：Bonac Corporation

  公开号：EP2722335A1

  公开（公告）日：2014-04-23

  The present invention provides a process for preparing an isotope-containing phosphate compound easily. The process for preparing an isotope-containing phosphate compound according to the present invention includes the step of: oxidizing a trivalent phosphorus compound with an oxidizing agent containing an isotope to synthesize a pentavalent phosphate compound to which the isotope has been introduced. The present invention preferably is applied to the synthesis of nucleic acids such as DNA and RNA, for example. The isotope preferably is a stable isotope. The oxidizing agent preferably is H218O, 3H-1,2-benzodithiol 3-one 1,1-dioxide having 34S, or a diisopropylethylamine-borane complex having 10B, for example.

  本发明提供了一种易于制备含同位素磷酸盐化合物的工艺。根据本发明制备含同位素磷酸盐化合物的工艺包括以下步骤：用含同位素的氧化剂氧化三价磷化合物，合成引入同位素的五价磷酸盐化合物。本发明最好用于合成核酸，例如 DNA 和 RNA。同位素最好是稳定同位素。氧化剂最好是 H218O、具有 34S 的 3H-1,2-苯并二硫醇-3-酮 1,1-二氧化物或具有 10B 的二异丙基乙胺硼烷络合物等。