(2S,3aS,6aS)-6-(tert-Butyl-dimethyl-silanyloxy)-2-methoxy-2,3,4,6a-tetrahydro-cyclopenta[b]furan-3a-ol | 200931-60-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (2S,3aS,6aS)-6-(tert-Butyl-dimethyl-silanyloxy)-2-methoxy-2,3,4,6a-tetrahydro-cyclopenta[b]furan-3a-ol
• 英文别名: (2S,3aS,6aS)-6-[tert-butyl(dimethyl)silyl]oxy-2-methoxy-2,3,4,6a-tetrahydrocyclopenta[b]furan-3a-ol
• CAS: 200931-60-8
• 化学式: C₁₄H₂₆O₄Si
• 分子量: 286.444
• InChiKey: KTEMDEZRCLNAPT-SCRDCRAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.79
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,3aS,6aS)-6-(tert-Butyl-dimethyl-silanyloxy)-2-methoxy-2,3,4,6a-tetrahydro-cyclopenta[b]furan-3a-ol 在 硼烷四氢呋喃络合物 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 33.0h， 生成 (1R,3S,5R,8S)-8-{[(tert-butyl)dimethylsilyl]oxy}-5-hydroxy-3-methoxy-2-oxabicyclo[3.3.0]octan-7-one
  参考文献：
  名称：

  Nucleic-Acid Analogs with Restricted Conformational Flexibility in the Sugar-Phosphate Backbone (`Bicyclo-DNA'), Part 7, Synthesis and Properties of Oligodeoxynucleotides Containing [(3′S,5′S,6′R)-6′-Amino-2′-deoxy-3′,5′-ethano-β-D-ribofuranosyl]thymine (=(6′R)-6′-Amino-bicyclo-thymidine)

  摘要：

  We describe the synthesis of the acetamido- and trifluoroacetamido-functionalized bicyclo-thymidines 11 and 12, starting from the silyl enol ether 1, in 6 steps. These nucleosides were converted to the corresponding cyanoethyl phosphoramidite building blocks 16 and 17 and subsequently incorporated into the homothymidylate decamers 18-22. Upon deprotection of the oligomers, the trifluoroacetamido functions were cleaved, leaving behind a free amino function in the sugar-phosphate backbone that is protonated at neutral pH, giving rise to partially zwitterionic oligonucleotides. Pairing properties with the complementary DNA oligomer d(A(10)), as determined by UV/melting curves, revealed a slightly increased stability of the duplex d(A(10)) . 20, in which the decathymidylate sequence shows an alternating arrangement of natural thymidine and amino-bicyclo-thymidine residues, relative to the natural reference duplex. The dependence of T-m on the salt concentration of the medium is reduced in this case. Duplex destabilization occurs if the amino-bicyclo-thymidine residues are replaced by the charge-neutral acetamido-bicyclo-nucleosides (e.g., d(A(10)) . 22), most probably due to steric interference of the acetamido substituent with the backbone P-O(5') bond.

  DOI：

  10.1002/(sici)1522-2675(19991110)82:11<1813::aid-hlca1813>3.0.co;2-0
• 作为产物：
  描述：

  (1R,5R,6S)-6-(2'-hydroxyethyl)-3,3-dimethyl-2,4-dioxabicyclo[3.3.0]octan-6-ol 在 Amberlyst 15 (H⁺ form) 、 戴斯-马丁氧化剂 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 为溶剂， 反应 24.75h， 生成 (2S,3aS,6aS)-6-(tert-Butyl-dimethyl-silanyloxy)-2-methoxy-2,3,4,6a-tetrahydro-cyclopenta[b]furan-3a-ol
  参考文献：
  名称：

  在糖磷酸骨架“ Tricyclo-DNA”中具有限制性构象灵活性的核酸类似物。部分1的制备[（5' - [R，6' - [R）-2'-脱氧-3'，5'-亚乙基-5'，6'-甲基- β-d-D-呋喃核糖基]胸腺嘧啶和腺嘌呤，和用于寡核苷酸合成的相应亚磷酰胺†

  摘要：

  描述了用于寡核苷酸合成的三环-脱氧核苷类似物1和2以及相应的氰乙基亚磷酰胺结构单元16和21的合成。这些三环脱氧核苷类似物与新近引入的双环脱氧核苷的区别在于，一个附加的环丙烷单元连接到后者的中心C（5'）和C（6'）（参见图1），因此代表该环的另一个成员。一类具有约束构象灵活性的核苷类似物。三环脱氧核苷的合成通过非对映选择性卡宾除了对映异构纯的甲硅烷基烯醇任一实现8 / 9和一个Vorbrüggen三环碳水化合物单元的缩合10 / 11与在原位全硅烷化胸腺嘧啶和Ñ 6苯甲酰基腺嘌呤。叔OHC（5'）的选择性三苯甲基化和OHC（3'）的1和2的膦酰化得到相应的亚磷酰胺16和21。通过1 H-NMR-NOE光谱学证实了新引入的环丙烷环的“ exo ”-构型。核苷类似物1和14（2和19的C（1'）处的α-D和β-D构型，分别通过1 H-NMR-NOE光谱和NOESY进行分配。建模研究β-d-异

  DOI：

  10.1002/hlca.19970800812

文献信息

• [EN] TRICYCLO-DNA NUCLEOSIDE PRECURSORS AND PROCESSES FOR PREPARING THE SAME<br/>[FR] PRÉCURSEURS NUCLÉOSIDIQUES TRICYCLO-ADN ET PROCÉDÉS DE PRÉPARATION ASSOCIÉS
  申请人：SYNTHENA AG

  公开号：WO2019142135A1

  公开（公告）日：2019-07-25

  The present invention relates to a process for preparing tc-DNA nucleoside precursors, the resulting tc-DNA nucleosides, and oligonucleotides comprising such tc-DNA nucleosides. In an embodiment of the invention, the process includes use of a carbene precursor. In an embodiment, the invention includes processes for preparing a tc-DNA nucleoside precursor of Formula (I), Formula (II), Formula (III), Formula (IV), Formula (V) or Formula (VI).

  本发明涉及一种制备tc-DNA核苷前体的过程，所得的tc-DNA核苷，以及包含这种tc-DNA核苷的寡核苷酸。在本发明的一个实施例中，该过程包括使用碳烯前体。在一种实施例中，该发明包括制备公式(I)、公式(II)、公式(III)、公式(IV)、公式(V)或公式(VI)的tc-DNA核苷前体的过程。
• [EN] TRICYCLIC NUCLEOSIDES AND OLIGOMERIC COMPOUNDS PREPARED THEREFROM<br/>[FR] NUCLÉOSIDES TRICYCLIQUES ET COMPOSÉS OLIGOMÈRES PRÉPARÉS À PARTIR DE CEUX-CI
  申请人：UNIVERSITÄT BERN

  公开号：WO2014140348A1

  公开（公告）日：2014-09-18

  The present invention provides fluorine substituted tricyclic nucleosides of formula (I) wherein: the substituents are as defined in the claims. The present invention further provides oligomeric compounds prepared therefrom. Incorporation of one or more of the tricyclic nucleosides into an oligomeric compound enhances one or more properties of the oligomeric compound. Such oligomeric compounds can also be included in double stranded compositions.

  本发明提供了式（I）的氟取代三环核苷，其中：取代基如权利要求中所定义。本发明还提供了由此制备的寡聚化合物。将一种或多种三环核苷并入寡聚化合物中，可以增强该寡聚化合物的一个或多个性质。这种寡聚化合物也可以包含在双链组合物中。
• Synthesis and Properties of 6′-Fluoro-tricyclo-DNA
  作者：Michal Medvecky、Alena Istrate、Christian J. Leumann

  DOI：10.1021/acs.joc.5b00184

  日期：2015.4.3

  The synthesis of the two fluorinated tricyclic nucleosides 6′-F-tc-T and 6′-F-tc-5MeC, as well as the corresponding building blocks for oligonucleotide assembly, was accomplished. An X-ray analysis of N4-benzoylated 6′-F-tc-5MeC reavealed a 2′-exo (north) conformation of the furanose ring, characterizing it as an RNA mimic. In contrast to observations in the bicyclo-DNA series, no short contact between

  完成了两个氟化三环核苷6'-F-tc-T和6'-F-tc-5 Me C的合成，以及用于寡核苷酸组装的相应构件。N 4-苯甲酰化的6'-F- tc - 5Me C的X射线分析表明呋喃糖环的2'-exo（北部）构象消失，将其表征为RNA模拟物。与双环DNA系列中的观察相反，在氟原子和碱基的H6之间没有观察到短暂的接触，让人联想到非经典的F··H氢键。用互补RNA修饰的寡聚脱氧核苷酸的T m测量结果显示，序列依赖性的双链稳定曲线略有变化，最大ΔT m/ mod值对于6'-F-tc- 5Me C为+4.5°C，对于6'-F-tc-T为+1°C。与亲本tc-修饰的寡核苷酸相比，未检测到T m的相关变化，这归因于氟取代基在RNA亲和力中具有中性作用。通过CD光谱对具有DNA和RNA的双链体进行结构分析，揭示了由6'-F-tc-核苷诱导的B型向A型构象的转变。这不是特定的“氟效应”，因为在母体tc修饰物