2',3'-O-isopropylidene-5'-O-(di-tert-butylphosphoramidite)-6-thioinosine | 1375103-71-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 2',3'-O-isopropylidene-5'-O-(di-tert-butylphosphoramidite)-6-thioinosine
• 英文别名: Di-tert-butyl (((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-thioxo-3,6-dihydro-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl) phosphate；[(3aR,4R,6R,6aR)-2,2-dimethyl-4-(6-sulfanylidene-3H-purin-9-yl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl ditert-butyl phosphate
• CAS: 1375103-71-1
• 化学式: C₂₁H₃₃N₄O₇PS
• 分子量: 516.555
• InChiKey: QQFBRLIRKFVXGH-SCFUHWHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.66
• 重原子数：
  34.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  118.95
• 氢给体数：
  1.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylidene-5'-O-(di-tert-butylphosphoramidite)-6-thioinosine 在 2,2'-二硫二吡啶 、 magnesium sulfate 、 三苯基膦 、 三氟乙酸 、 manganese(ll) chloride 作用下， 以 水 、 formamide 、 二甲基亚砜 为溶剂， 反应 25.0h， 生成 nicotinamide 6-mercaptopurine 5'-dinucleotide
  参考文献：
  名称：

  Aberrant Cyclization Affords a C-6 Modified Cyclic Adenosine 5′-Diphosphoribose Analogue with Biological Activity in Jurkat T Cells

  摘要：

  Two nicotinamide adenine dinucleotide (NAD(+)) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD(+) (6-N-methyl nicotinamide adenosine 5'-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5'-diphosphoribose, 11), whereas 6-thio NHD+ (nicotinamide 6-mercaptopurine 5'-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5'-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5'-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1-cIDPR-induced Ca2+ release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5'-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1-cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling.

  DOI：

  10.1021/jm201127y
• 作为产物：
  描述：

  在 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 2-巯基乙醇 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 2',3'-O-isopropylidene-5'-O-(di-tert-butylphosphoramidite)-6-thioinosine
  参考文献：
  名称：

  Aberrant Cyclization Affords a C-6 Modified Cyclic Adenosine 5′-Diphosphoribose Analogue with Biological Activity in Jurkat T Cells

  摘要：

  Two nicotinamide adenine dinucleotide (NAD(+)) analogues modified at the 6 position of the purine ring were synthesized, and their substrate properties toward Aplysia californica ADP-ribosyl cyclase were investigated. 6-N-Methyl NAD(+) (6-N-methyl nicotinamide adenosine 5'-dinucleotide 10) hydrolyzes to give the linear 6-N-methyl ADPR (adenosine 5'-diphosphoribose, 11), whereas 6-thio NHD+ (nicotinamide 6-mercaptopurine 5'-dinucleotide, 17) generates a cyclic dinucleotide. Surprisingly, NMR correlation spectra confirm this compound to be the N1 cyclic product 6-thio N1-cIDPR (6-thio cyclic inosine 5'-diphosphoribose, 3), although the corresponding 6-oxo analogue is well-known to cyclize at N7. In Jurkat T cells, unlike the parent cyclic inosine 5'-diphosphoribose N1-cIDPR 2, 6-thio N1-cIDPR antagonizes both cADPR- and N1-cIDPR-induced Ca2+ release but possesses weak agonist activity at higher concentration. 3 is thus identified as the first C-6 modified cADPR (cyclic adenosine 5'-diphosphoribose) analogue antagonist; it represents the first example of a fluorescent N1-cyclized cADPR analogue and is a new pharmacological tool for intervention in the cADPR pathway of cellular signaling.

  DOI：

  10.1021/jm201127y