N²-isobutyryl-3',5'-di-O-levulinoyl-2'-deoxy-β-L-guanosine | 1245770-88-0

• 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: N²-isobutyryl-3',5'-di-O-levulinoyl-2'-deoxy-β-L-guanosine
• 英文别名: [(2S,3R,5S)-5-[2-(2-methylpropanoylamino)-6-oxo-1H-purin-9-yl]-3-(4-oxopentanoyloxy)oxolan-2-yl]methyl 4-oxopentanoate
• CAS: 1245770-88-0
• 化学式: C₂₄H₃₁N₅O₉
• 分子量: 533.538
• InChiKey: VNUHPDDOJNVITO-IKGGRYGDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  38
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  184
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N²-isobutyryl-3',5'-di-O-levulinoyl-2'-deoxy-β-L-guanosine 在 Candida antarctica lipase B 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 42.0h， 以80%的产率得到[(2S,3R,5S)-2-(hydroxymethyl)-5-[2-(2-methylpropanoylamino)-6-oxo-1H-purin-9-yl]oxolan-3-yl] 4-oxopentanoate
  参考文献：
  名称：

  Enzymatic Parallel Kinetic Resolution of Mixtures of d/l 2′-Deoxy and Ribonucleosides: An Approach for the Isolation of β-l-Nucleosides

  摘要：

  We have developed a lipase-catalyzed parallel kinetic resolution of mixtures of beta-D/L-nucleosides. The opposite selectivity during acylation exhibited by Pseudomonas cepacia lipase (PSL-C) with beta-D- and beta-L-nucleosides furnished acylated compounds that have different R-f values. As a consequence, isolation of both products was achieved by simple column chromatography. Computer modeling of the transition-state analogues during acylation of beta-D- and beta-L-2'-deoxycytidine with PSL-C was carried out to explain the high selectivity. PSL-C favored the 3'-O-levulination of the beta-D enantiomer, whereas the 5'-OH group was acylated in 2'-deoxy-beta-L-cytidine. In both cases, the cytosine base was placed in the alternate hydrophobic pocket of PSL's substrate-binding site, where it can form extra hydrogen bonds (in addition to the five essential catalytically relevant hydrogen bonds) that stabilize these intermediates catalyzing the selective acylation of beta-D/L-nucleosides.

  DOI：

  10.1021/jo101368z
• 作为产物：
  描述：

  乙酰丙酸 、 N-isobutyryl-β-L-2'-deoxyguanosine 在 4-二甲氨基吡啶 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以93%的产率得到N²-isobutyryl-3',5'-di-O-levulinoyl-2'-deoxy-β-L-guanosine
  参考文献：
  名称：

  Enzymatic Parallel Kinetic Resolution of Mixtures of d/l 2′-Deoxy and Ribonucleosides: An Approach for the Isolation of β-l-Nucleosides

  摘要：

  We have developed a lipase-catalyzed parallel kinetic resolution of mixtures of beta-D/L-nucleosides. The opposite selectivity during acylation exhibited by Pseudomonas cepacia lipase (PSL-C) with beta-D- and beta-L-nucleosides furnished acylated compounds that have different R-f values. As a consequence, isolation of both products was achieved by simple column chromatography. Computer modeling of the transition-state analogues during acylation of beta-D- and beta-L-2'-deoxycytidine with PSL-C was carried out to explain the high selectivity. PSL-C favored the 3'-O-levulination of the beta-D enantiomer, whereas the 5'-OH group was acylated in 2'-deoxy-beta-L-cytidine. In both cases, the cytosine base was placed in the alternate hydrophobic pocket of PSL's substrate-binding site, where it can form extra hydrogen bonds (in addition to the five essential catalytically relevant hydrogen bonds) that stabilize these intermediates catalyzing the selective acylation of beta-D/L-nucleosides.

  DOI：

  10.1021/jo101368z

文献信息

• Enzymatic Parallel Kinetic Resolution of Mixtures of <scp>d</scp>/<scp>l</scp> 2′-Deoxy and Ribonucleosides: An Approach for the Isolation of β-<scp>l</scp>-Nucleosides
  作者：Saúl Martínez-Montero、Susana Fernández、Yogesh S. Sanghvi、Vicente Gotor、Miguel Ferrero

  DOI：10.1021/jo101368z

  日期：2010.10.1

  We have developed a lipase-catalyzed parallel kinetic resolution of mixtures of beta-D/L-nucleosides. The opposite selectivity during acylation exhibited by Pseudomonas cepacia lipase (PSL-C) with beta-D- and beta-L-nucleosides furnished acylated compounds that have different R-f values. As a consequence, isolation of both products was achieved by simple column chromatography. Computer modeling of the transition-state analogues during acylation of beta-D- and beta-L-2'-deoxycytidine with PSL-C was carried out to explain the high selectivity. PSL-C favored the 3'-O-levulination of the beta-D enantiomer, whereas the 5'-OH group was acylated in 2'-deoxy-beta-L-cytidine. In both cases, the cytosine base was placed in the alternate hydrophobic pocket of PSL's substrate-binding site, where it can form extra hydrogen bonds (in addition to the five essential catalytically relevant hydrogen bonds) that stabilize these intermediates catalyzing the selective acylation of beta-D/L-nucleosides.