(1R,3R,5S,7S,8R)-8-{[(tert-butyl)dimethylsilyl]oxy}-3-methoxy-2-oxabicyclo[3.3.0]octan-5,7-diol | 258504-91-5

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (1R,3R,5S,7S,8R)-8-{[(tert-butyl)dimethylsilyl]oxy}-3-methoxy-2-oxabicyclo[3.3.0]octan-5,7-diol
• 英文别名: (2R,3aS,5S,6R,6aR)-6-[tert-butyl(dimethyl)silyl]oxy-2-methoxy-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-3a,5-diol
• CAS: 258504-91-5
• 化学式: C₁₄H₂₈O₅Si
• 分子量: 304.459
• InChiKey: WFHVHLMMSACHKR-KSFQGOMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.63
• 重原子数：
  20.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  68.15
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (1R,3R,5S,7S,8R)-8-{[(tert-butyl)dimethylsilyl]oxy}-3-methoxy-2-oxabicyclo[3.3.0]octan-5,7-diol 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以740 mg的产率得到(1R,3R,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：

  (2R,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 作用下， 以 四氢呋喃 为溶剂， 反应 31.0h， 以91%的产率得到(1R,3R,5S,7S,8R)-8-{[(tert-butyl)dimethylsilyl]oxy}-3-methoxy-2-oxabicyclo[3.3.0]octan-5,7-diol
  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

文献信息

• Parallel synthesis and nucleic acid binding properties of C(6′)-α-functionalized bicyclo-DNA
  作者：Peter Šilhár、Christian J. Leumann

  DOI：10.1016/j.bmc.2010.09.064

  日期：2010.11.15

  Two novel bicyclo-T nucleosides carrying a hydroxyl or a carboxymethyl substituent in C(6′)-α-position were prepared and incorporated into oligodeoxynucleotides. During oligonucleotide deprotection the carboxymethyl substituent was converted into different amide substituents in a parallel way. Tm-measurements showed no dramatic differences in both, thermal affinity and mismatch discrimination, compared

  制备了两个在C（6'）-α-位带有羟基或羧甲基取代基的新型双环-T核苷，并将其掺入寡脱氧核苷酸中。在寡核苷酸脱保护过程中，羧甲基取代基以平行方式转化为不同的酰胺取代基。与未修饰的寡核苷酸相比，T m-测量在热亲和力和错配辨别力上均没有显示出显着差异。羧甲基取代基的合成后修饰原则上可以并行制备在C（6'）处带有多个取代基的寡核苷酸文库。另外，可以将官能团置于DNA双螺旋中的独特位置。
• Synthesis and Properties of Isobicyclo-DNA
  作者：Anna-Barbara Gerber、Christian J. Leumann

  DOI：10.1002/chem.201300487

  日期：2013.5.27

  AbstractWe present the synthesis of the isobicyclo‐DNA building blocks with the nucleobases A, C, G and T, as well as biophysical and biological properties of oligonucleotides derived thereof. The synthesis of the sugar part was achieved in 5 steps starting from a known intermediate of the tricyclo‐DNA synthesis. Dodecamers containing single isobicyclo‐thymidine incorporations, fully modified A‐ and T‐containing sequences, and fully modified oligonucleotides containing all four bases were synthesized and characterized. Isobicyclo‐DNA forms stable duplexes with natural nucleic acids with a pronounced preference for DNA over RNA as complements. The most stable duplexes, however, arise by self‐pairing. Isobicyclo‐DNA forms preferentially B‐DNA‐like duplexes with DNA and A‐like duplexes with complementary RNA as determined by circular dichroism (CD) spectroscopy. Self‐paired duplexes show a yet unknown structure, as judged from CD spectroscopy. Biochemical tests revealed that isobicyclo‐DNA is stable in fetal bovine serum and does not elicit RNaseH activity.