(1R,5R,6R,8S)-8-(tert-butyldimethylsilyloxy)-1-tert-butyldimethylsilyloxymethyl-6-(uracil-1-yl)-7-oxabicyclo[3.2.1]oct-2-ene | 913972-66-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (1R,5R,6R,8S)-8-(tert-butyldimethylsilyloxy)-1-tert-butyldimethylsilyloxymethyl-6-(uracil-1-yl)-7-oxabicyclo[3.2.1]oct-2-ene
• 英文别名: 1-[(1R,5R,7R,8S)-8-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-6-oxabicyclo[3.2.1]oct-3-en-7-yl]pyrimidine-2,4-dione
• CAS: 913972-66-4
• 化学式: C₂₄H₄₂N₂O₅Si₂
• 分子量: 494.779
• InChiKey: MPGYVXZQWLPTHL-SSYAZSBWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.79
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,5R,6R,8S)-8-(tert-butyldimethylsilyloxy)-1-tert-butyldimethylsilyloxymethyl-6-(uracil-1-yl)-7-oxabicyclo[3.2.1]oct-2-ene 在 吡啶 、 四丁基氟化铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 47.0h， 生成 (1R,5R,6R,8S)-8-(2-cyanoethoxy(diisopropylamino)phosphinoxy)-1-(4,4'-dimethoxytrityloxymethyl)-6-(uracil-1-yl)-7-oxabicyclo[3.2.1]oct-2-ene
  参考文献：
  名称：

  Analogues of a Locked Nucleic Acid with Three-Carbon 2‘,4‘-Linkages:  Synthesis by Ring-Closing Metathesis and Influence on Nucleic Acid Duplex Stability and Structure

  摘要：

  Two bicyclic 2'-deoxynucleoside analogues containing a saturated and an unsaturated three-carbon 2', 4'-linkage, respectively, have been synthesized using a ring-closing metathesis-based linear strategy starting from uridine. Both analogues have been incorporated into oligodeoxynucleotide sequences and increased the stability of DNA:RNA hybrid duplexes (Delta T-m similar to 2.5-5.0 degrees C per modification) and decreased the stability of dsDNA duplexes (Delta T-m similar to 2.5-1.0 degrees C per modification). CD spectroscopy revealed that the bicyclic nucleosides induced formation of A-type-like duplexes albeit to a lesser degree than found for locked nucleic acid (LNA) monomers. From the CD data and UV melting analysis, we propose that the 2'-oxygen atom of the bicyclic moiety is essential for the formation of stabilized A-type-like dsDNA but not for the formation of a stabilized A-type DNA:RNA hybrid.

  DOI：

  10.1021/jo061225g
• 作为产物：
  描述：

  2'-deoxy-2'-C-allyl-3',5'-di-O-(tert-butyldimethylsilyl)-4'-C-vinyluridine 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 以96%的产率得到(1R,5R,6R,8S)-8-(tert-butyldimethylsilyloxy)-1-tert-butyldimethylsilyloxymethyl-6-(uracil-1-yl)-7-oxabicyclo[3.2.1]oct-2-ene
  参考文献：
  名称：

  Analogues of a Locked Nucleic Acid with Three-Carbon 2‘,4‘-Linkages:  Synthesis by Ring-Closing Metathesis and Influence on Nucleic Acid Duplex Stability and Structure

  摘要：

  Two bicyclic 2'-deoxynucleoside analogues containing a saturated and an unsaturated three-carbon 2', 4'-linkage, respectively, have been synthesized using a ring-closing metathesis-based linear strategy starting from uridine. Both analogues have been incorporated into oligodeoxynucleotide sequences and increased the stability of DNA:RNA hybrid duplexes (Delta T-m similar to 2.5-5.0 degrees C per modification) and decreased the stability of dsDNA duplexes (Delta T-m similar to 2.5-1.0 degrees C per modification). CD spectroscopy revealed that the bicyclic nucleosides induced formation of A-type-like duplexes albeit to a lesser degree than found for locked nucleic acid (LNA) monomers. From the CD data and UV melting analysis, we propose that the 2'-oxygen atom of the bicyclic moiety is essential for the formation of stabilized A-type-like dsDNA but not for the formation of a stabilized A-type DNA:RNA hybrid.

  DOI：

  10.1021/jo061225g

文献信息

• Synthesis of Functionalized Carbocyclic Locked Nucleic Acid Analogues by Ring-Closing Diene and Enyne Metathesis and Their Influence on Nucleic Acid Stability and Structure
  作者：Surender Kumar、Marianne H. Hansen、Nanna Albæk、Signe I. Steffansen、Michael Petersen、Poul Nielsen

  DOI：10.1021/jo9013657

  日期：2009.9.4

  due to three-carbon linkages between the 2′- and 4′-positions have been prepared by ring-closing diene or enyne metathesis. The alkene or 1,3-diene hereby introduced in the bicyclic system is further derivatized, the latter showing the expected potential for Diels−Alder reactions. Four derivatives that are saturated or unsaturated as well as functionalized at the 2′−4′-linkage are incorporated into

  一系列双环2'-脱氧核苷，被锁在N通过闭环二烯或烯炔复分解制备了由于2'-和4'-位之间的三碳键合而形成的α-型构象。由此引入双环体系中的烯烃或1，3-二烯被进一步衍生化，后者显示出狄尔斯-阿尔德反应的预期潜力。将饱和或不饱和以及在2'-4'链上官能化的四种衍生物掺入寡脱氧核苷酸中，并研究它们对互补RNA和DNA的亲和力。观察到对互补RNA的亲和力大大提高，尤其是在双环系统上连接了额外的羟基时。另一方面，获得了对互补单链DNA的降低的亲和力，而仅发现了对形成三链体的寡核苷酸序列的很小的影响。因此，可以看到强烈的RNA选择性核酸识别，可以得出结论，2'-氧原子对于DNA：RNA双链的形成不如对DNA：DNA双链的形成重要。然而，双链体形成中2'-氧的缺乏可以部分被2'-4'-键周围的其他亲水部分所补偿，这表明结构水的结合非常重要。
• Two Carbocyclic Locked Nucleic Acid Analogues Give Structural Information about the Role of Hydration in A-Type Duplexes
  作者：Nanna Albæk、Michael Petersen、Poul Nielsen

  DOI：10.1080/15257770701544377

  日期：2007.11.26

  Two locked nucleic acid (LNA) analogues with three-carbon 24 linkages, saturated or unsaturated, are synthesized using a ring-closing metathesis based strategy. Strongly stabilized duplexes with complementary RNA and slightly destabilized duplexes with complementary DNA are observed. CD-spectroscopy indicates a less pronounced shift toward A-type duplexes compared to LNA. These results combining a strong N-type conformation with the absence of a 2'-oxygen demonstrate a stronger importance of minor groove hydration in an intermediate duplex type than in an A-type duplex.
• Analogues of a Locked Nucleic Acid with Three-Carbon 2‘,4‘-Linkages:  Synthesis by Ring-Closing Metathesis and Influence on Nucleic Acid Duplex Stability and Structure
  作者：Nanna Albæk,、Michael Petersen、Poul Nielsen

  DOI：10.1021/jo061225g

  日期：2006.9.1

  Two bicyclic 2'-deoxynucleoside analogues containing a saturated and an unsaturated three-carbon 2', 4'-linkage, respectively, have been synthesized using a ring-closing metathesis-based linear strategy starting from uridine. Both analogues have been incorporated into oligodeoxynucleotide sequences and increased the stability of DNA:RNA hybrid duplexes (Delta T-m similar to 2.5-5.0 degrees C per modification) and decreased the stability of dsDNA duplexes (Delta T-m similar to 2.5-1.0 degrees C per modification). CD spectroscopy revealed that the bicyclic nucleosides induced formation of A-type-like duplexes albeit to a lesser degree than found for locked nucleic acid (LNA) monomers. From the CD data and UV melting analysis, we propose that the 2'-oxygen atom of the bicyclic moiety is essential for the formation of stabilized A-type-like dsDNA but not for the formation of a stabilized A-type DNA:RNA hybrid.