(1R,2S,3R,5S)-3-Benzyloxy-2-benzyloxymethyl-6-oxa-bicyclo[3.1.0]hexane | 873298-16-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1R,2S,3R,5S)-3-Benzyloxy-2-benzyloxymethyl-6-oxa-bicyclo[3.1.0]hexane
• 英文别名: (1R,2S,3R,5S)-3-(Benzyloxy)-2-[(benzyloxy)methyl]-6-oxabicyclo[3.1.0]hexane；(1R,2S,3R,5S)-3-phenylmethoxy-2-(phenylmethoxymethyl)-6-oxabicyclo[3.1.0]hexane
• CAS: 873298-16-9
• 化学式: C₂₀H₂₂O₃
• 分子量: 310.393
• InChiKey: YPDRJNPIGFCETD-ZGXWSNOMSA-N

物化性质

• 沸点：
  427.9±40.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷、乙醚、乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  31
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,2S,3R,5S)-3-Benzyloxy-2-benzyloxymethyl-6-oxa-bicyclo[3.1.0]hexane 在 sodium hydroxide 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1'R,2'S,3'R,4'R)-1-(4-benzyloxy-3-benzyloxymethyl-2-hydroxycyclopentyl)uracil
  参考文献：
  名称：

  Synthesis and hybridization properties ofl-oligodeoxynucleotide analogues fixed in a low anti glycosyl conformation

  摘要：

  我们合成了核苷类似物的 L 型对映体（cU 和 cA），其糖基键以低反构象（ap 糖基构象，χ ≈ 180°）固定，并将其加入寡核苷酸中，评估其与天然 DNA 和 RNA 序列的杂交能力。虽然将修饰的核苷掺入寡核苷酸中会降低与未修饰的互补 DNA 序列的杂交能力，但完全取代的 12 聚体（cU12 和 cA12）仍能保持与未修饰的互补 DNA 12 聚体的杂交能力，而不管它们的非天然 L 手性如何。cU12 与 rA12 形成的双链比相应的天然 12 聚体（dT12）更稳定，而 cA12 则不能与 rU12 杂交。基于 cU12-rA12 的模型结构，我们对这些实验结果进行了讨论。

  DOI：

  10.1039/b312276j
• 作为产物：
  描述：

  (1R,2S)-2-(苄氧甲基)-3-环戊烯-1-醇 在 叔丁基过氧化氢 、 bis(acetylacetonate)oxovanadium 、 四丁基碘化铵 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (1R,2S,3R,5S)-3-Benzyloxy-2-benzyloxymethyl-6-oxa-bicyclo[3.1.0]hexane
  参考文献：
  名称：

  BMS-200475, a novel carbocyclic 2′-deoxyguanosine analog with potent and selective anti-hepatitis B virus activity in vitro

  摘要：

  BMS-200475, a novel carbocyclic analog of 2'-deoxyguanosine, is a potent inhibitor of hepatitis B virus in vitro (ED(50)=3 nM) with relatively low cytotoxicity (CC50=21-120 mu M). A practical 10-step asymmetric synthesis was developed affording BMS-200475 in 18% overall chemical yield and >99% optical purity. The enantiomer of EMS-200475 as well as the adenine, thymine, and iodouracil analogs are much less active. (C) 1997, Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(96)00594-x

文献信息

• Design and Racemic Synthesis of Conformationally Restricted Carbocyclic Pyrimidine Nucleoside Analogs Based on the Structure of the L-Nucleoside Residue in Heterochiral DNA.
  作者：Hidehito URATA、Hidetaka MIYAGOSHI、Hitoshi KAKUYA、Hideki TOKUMOTO、Takuya KAWAHATA、Toru OTAKE、Masao AKAGI

  DOI：10.1248/cpb.46.458

  日期：——

  Carbocyclic pyrimidine nucleoside analogs which have restricted glycosidic conformation at chi approximately 180 degrees were designed, based on the conformational features of the L-nucleotide residue in heterochiral DNA, and synthesized. The synthesis of (+/-)-carbocyclic 6,6'-O-cyclo-2'-deoxyuridine was achieved via bromination and subsequent intramolecular cyclization of carbocyclic 6'beta-hydroxy-2'-deoxyuridine

  基于异手性DNA中L-核苷酸残基的构象特征，设计了在大约180度具有受限糖苷构象的碳环嘧啶核苷类似物，并进行了合成。（+/-）-碳环6,6'-O-环-2'-脱氧尿苷的合成是通过碳环6'β-羟基-2'-脱氧尿苷的溴化和随后的分子内环化来实现的。（4-）-碳环6,6'-O-环-2'-脱氧胞苷通过4-三唑中间体由受保护的碳环6,6'-O-环-2'-脱氧尿苷合成。
• Racemic synthesis of carbocyclic purine nucleoside analogues with restricted glycosyl conformation
  作者：Hidehito Urata、Hidetaka Miyagoshi、Takashi Yumoto、Masao Akagi

  DOI：10.1039/a901884k

  日期：——

  Carbocyclic purine nucleoside analogues which have restricted glycosyl conformation at χ ≈ 180° were designed, based on the conformational features of the L-nucleotide residue in heterochiral DNA, and synthesized. The synthesis of (±)-carbocyclic 8,6′-O-anhydro-8,6′-dihydroxy-2′-deoxyadenosine 3 was achieved by intramolecular cyclization of the 8-bromo-6′-O-tosyl-2′-deoxyadenosine derivative. (±)-Carbocyclic

  碳环嘌呤核苷类似物，其在具有受限制的构象糖χ 听，说：180°设计的基础上，构象特征大号个核苷酸残基在异向DNA，和合成。的合成（±） -碳环8,6'- Ô -anhydro-8,6'二羟基-2'-脱氧腺苷3通过的分子内环化实现8-溴-6'- ö甲苯磺酰基-2'-脱氧腺苷衍生物。（±） -碳环8,6'- Ô -anhydro-8,6'二羟基-2'-脱氧鸟苷4从碳环2,6-二氨基嘌呤核苷衍生物合成经由碳环8-溴-6'- ø -甲磺酰基-2'-脱氧鸟苷衍生物。
• BMS-200475, a novel carbocyclic 2′-deoxyguanosine analog with potent and selective anti-hepatitis B virus activity in vitro
  作者：G.S. Bisacchi、S.T. Chao、C. Bachard、J.P. Daris、S. Innaimo、G.A. Jacobs、O. Kocy、P. Lapointe、A. Martel、Z. Merchant、W.A. Slusarchyk、J.E. Sundeen、M.G. Young、R. Colonno、R. Zahler

  DOI：10.1016/s0960-894x(96)00594-x

  日期：1997.1

  BMS-200475, a novel carbocyclic analog of 2'-deoxyguanosine, is a potent inhibitor of hepatitis B virus in vitro (ED(50)=3 nM) with relatively low cytotoxicity (CC50=21-120 mu M). A practical 10-step asymmetric synthesis was developed affording BMS-200475 in 18% overall chemical yield and >99% optical purity. The enantiomer of EMS-200475 as well as the adenine, thymine, and iodouracil analogs are much less active. (C) 1997, Elsevier Science Ltd.
• Synthesis and hybridization properties of<scp>l</scp>-oligodeoxynucleotide analogues fixed in a low anti glycosyl conformation
  作者：Hidehito Urata、Hidetaka Miyagoshi、Tetsuya Kumashiro、Takashi Yumoto、Keiji Mori、Keiko Shoji、Keigo Gohda、Masao Akagi

  DOI：10.1039/b312276j

  日期：——

  We have synthesized L-type enantiomers (cU and cA) of nucleoside analogues, whose glycosyl bonds are fixed in a low anti conformation (ap glycosyl conformation, χ ≈ 180°), and incorporated them into oligonucleotides to evaluate the hybridization ability with natural DNA and RNA sequences. Although the incorporation of the modified nucleosides into oligonucleotides decreased the hybridization ability with unmodified complementary DNA sequences, the fully-substituted 12mers (cU12 and cA12) still retained the hybridization ability with the complementary unmodified DNA 12mers, regardless of their unnatural L-chirality. In contrast, cU12 and cA12 showed different hybridization behavior with complementary unmodified RNA 12mers. cU12 forms a more stable duplex with rA12 than the corresponding natural 12mer (dT12), whereas cA12 cannot hybridize with rU12. Based on the model structure of cU12–rA12, we discuss these experimental results.

  我们合成了核苷类似物的 L 型对映体（cU 和 cA），其糖基键以低反构象（ap 糖基构象，χ ≈ 180°）固定，并将其加入寡核苷酸中，评估其与天然 DNA 和 RNA 序列的杂交能力。虽然将修饰的核苷掺入寡核苷酸中会降低与未修饰的互补 DNA 序列的杂交能力，但完全取代的 12 聚体（cU12 和 cA12）仍能保持与未修饰的互补 DNA 12 聚体的杂交能力，而不管它们的非天然 L 手性如何。cU12 与 rA12 形成的双链比相应的天然 12 聚体（dT12）更稳定，而 cA12 则不能与 rU12 杂交。基于 cU12-rA12 的模型结构，我们对这些实验结果进行了讨论。