(3S,4R)-cis-N⁶-(4-(3-hydroxy-1,2,3,4-tetrahydrophenanthrenyl))-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine | 135560-88-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (3S,4R)-cis-N⁶-(4-(3-hydroxy-1,2,3,4-tetrahydrophenanthrenyl))-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine
• 英文别名: (3S,4R)-cis-N⁶-[4-(3-hydroxy-1,2,3,4-tetrahydrophenanthrenyl)]-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine；(3S,4R)-4-[[9-[(2R,4S,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]purin-6-yl]amino]-1,2,3,4-tetrahydrophenanthren-3-ol
• CAS: 135560-88-2；135636-90-7；141194-00-5；141194-01-6
• 化学式: C₃₆H₅₃N₅O₄Si₂
• 分子量: 676.019
• InChiKey: KFMPRXKWIYHMOJ-VJHPNSTISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.14
• 重原子数：
  47.0
• 可旋转键数：
  8.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  103.55
• 氢给体数：
  2.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  (3S,4R)-cis-N⁶-(4-(3-hydroxy-1,2,3,4-tetrahydrophenanthrenyl))-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine 在 吡啶 、 2,6-二甲基吡啶 、 四丁基氟化铵 、 lithium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.25h， 生成 (3S,4R)-N⁶-(4-(3-acetoxy-1,2,3,4-tetrahydrophenanthrenyl))-5'-O-(4,4'-dimethoxytrityl)-3'-O-<(N,N-diisopropylamino)(β-cyanoethoxy)phosphinyl>-2'-deoxyadenosine
  参考文献：
  名称：

  Synthesis and site-specific incorporation of a bay-region cis ring-opened tetrahydro epoxide-deoxyadenosine adduct into a DNA oligomer

  摘要：

  Chemical synthesis of the 1,2,3,4-tetrahydrophenanthrene 3,4-epoxide adducts resulting from benzylic, cis ring-opening of the epoxide by the exocyclic amino group of 2'-deoxyadenosine (dA) is described. The approach taken consists of coupling (+/-)-cis-3-hydroxy-4-amino-1,2,3,4-tetrahydrophenanthrene with a 6-fluoro analogue of dA in which the furanose hydroxyl groups are protected. The required amino alcohol was obtained by reaction of 1,2-dihydrophenanthrene with osmium tetraoxide to form the cis 3,4-diol, conversion to the trans chlorohydrin benzoate via its orthobenzoate, displacement of the benzylic chloride by azide, hydrolysis to the cis azido alcohol, and reduction to the racemic cis amino alcohol. Coupling of the amino alcohol with the 3',5'-bis-O-(tert-butyldimethylsilyl) derivative of 6-fluoro-9-(2-deoxy-beta-D-erythro-pentofuranosyl)purine results in a pair of diastereomers that are readily separated by HPLC on silica gel. Replacement of the previously used pyridine by 2,6-lutidine significantly improved the yield for the coupling step. Both adducts were acetylated on the hydroxyl group of the hydrocarbon and then desilylated on the sugar. Absolute configurations were assigned to the adducts on the basis of the shapes of their CD spectra. The 3S,4R diastereomer (derived from the more polar, late-eluting adduct) was blocked at the 5'-sugar hydroxyl group with the 4,4'-dimethoxytrityl group and allowed to react with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite to produce the desired activated nucleoside. Incorporation into the deoxynucleotide TpGpA*pGpT as the central base proceeded in good yield with minor modifications to the standard DNA synthesizer protocol.

  DOI：

  10.1021/jo00038a037
• 作为产物：
  描述：

  1,2-二氢菲 在 palladium on activated charcoal 吡啶 、 2,6-二甲基吡啶 、 四氧化锇 、 三甲基氯硅烷 、 sodium azide 、 六甲基二硅氧烷 、 氢气 、 sodium methylate 、 三乙胺 、 苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 20.0h， 生成 (3S,4R)-cis-N⁶-(4-(3-hydroxy-1,2,3,4-tetrahydrophenanthrenyl))-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyadenosine
  参考文献：
  名称：

  Synthesis and site-specific incorporation of a bay-region cis ring-opened tetrahydro epoxide-deoxyadenosine adduct into a DNA oligomer

  摘要：

  Chemical synthesis of the 1,2,3,4-tetrahydrophenanthrene 3,4-epoxide adducts resulting from benzylic, cis ring-opening of the epoxide by the exocyclic amino group of 2'-deoxyadenosine (dA) is described. The approach taken consists of coupling (+/-)-cis-3-hydroxy-4-amino-1,2,3,4-tetrahydrophenanthrene with a 6-fluoro analogue of dA in which the furanose hydroxyl groups are protected. The required amino alcohol was obtained by reaction of 1,2-dihydrophenanthrene with osmium tetraoxide to form the cis 3,4-diol, conversion to the trans chlorohydrin benzoate via its orthobenzoate, displacement of the benzylic chloride by azide, hydrolysis to the cis azido alcohol, and reduction to the racemic cis amino alcohol. Coupling of the amino alcohol with the 3',5'-bis-O-(tert-butyldimethylsilyl) derivative of 6-fluoro-9-(2-deoxy-beta-D-erythro-pentofuranosyl)purine results in a pair of diastereomers that are readily separated by HPLC on silica gel. Replacement of the previously used pyridine by 2,6-lutidine significantly improved the yield for the coupling step. Both adducts were acetylated on the hydroxyl group of the hydrocarbon and then desilylated on the sugar. Absolute configurations were assigned to the adducts on the basis of the shapes of their CD spectra. The 3S,4R diastereomer (derived from the more polar, late-eluting adduct) was blocked at the 5'-sugar hydroxyl group with the 4,4'-dimethoxytrityl group and allowed to react with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite to produce the desired activated nucleoside. Incorporation into the deoxynucleotide TpGpA*pGpT as the central base proceeded in good yield with minor modifications to the standard DNA synthesizer protocol.

  DOI：

  10.1021/jo00038a037