cyclo(3-methylsaligenyl)-5'-O-(2',3'-dideoxyadenosinyl)phosphate

• 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: cyclo(3-methylsaligenyl)-5'-O-(2',3'-dideoxyadenosinyl)phosphate
• 英文别名: 3-methyl-cyclosaligenyl-ddAMP；3-Me-cycloSal-ddAMP；9-[(2R,5S)-5-[(8-methyl-2-oxo-4H-1,3,2$l^{5}-benzodioxaphosphinin-2-yl)oxymethyl]tetrahydrofuran-2-yl]purin-6-amine；9-[(2R,5S)-5-[(8-methyl-2-oxo-4H-1,3,2λ5-benzodioxaphosphinin-2-yl)oxymethyl]oxolan-2-yl]purin-6-amine
• 化学式: C₁₈H₂₀N₅O₅P
• 分子量: 417.361
• InChiKey: OPEKMFYZJNOBCH-BWIOJWINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2',3'-双脱氧腺苷 在 叔丁基过氧化氢 、 N,N-二异丙基乙胺 作用下， 生成 cyclo(3-methylsaligenyl)-5'-O-(2',3'-dideoxyadenosinyl)phosphate
  参考文献：
  名称：

  Interaction of cycloSal-Pronucleotides with Cholinesterases from Different Origins. A Structure−Activity Relationship

  摘要：

  A large number of cycloSal-nucleotide triesters 1-49 have been studied concerning their ability to inhibit cholinesterases of different origins as well as to inhibit HIV replication in cell culture. It was shown that none of the triesters showed inhibitory effects against human acetylcholinesterase (AChE; isolated enzyme) as well as against AChE from beef erythrocytes and calf serum. In contrast, inhibition of butyrylcholinesterase (BChE) has been observed for some triesters in human and mouse serum. cycloSal pronucleotides showed strong competitive inhibition with respect to the substrate acetylcholine chloride (K-i/K-m: similar to2 x 10(-5)) and acted by time-dependent irreversible inhibition of the human serum BChE. Detailed studies demonstrated that the inhibitory effect against BChE is dependent on the nucleoside analogue, the substitution pattern of the cycloSal-moiety, and particularly on the stereochemistry at the phosphorus atom. Structural requirements to avoid the inhibition of BChE by cycloSal-nucleotide triesters have been elucidated in the reported study.

  DOI：

  10.1021/jm031032a

文献信息

• <i>cyclo</i>Sal-Pronucleotides of 2‘,3‘-Dideoxyadenosine and 2‘,3‘-Dideoxy-2‘,3‘-didehydroadenosine:  Synthesis and Antiviral Evaluation of a Highly Efficient Nucleotide Delivery System
  作者：Chris Meier、Tina Knispel、Erik De Clercq、Jan Balzarini

  DOI：10.1021/jm981096z

  日期：1999.5.1

  nucleosides ddA (2) and d4A (3) as judged by their log P values. In hydrolysis studies, 9 and 10 decomposed under mild aqueous basic conditions releasing solely ddAMP (7) and d4AMP (8), as well as the diols 14. Further hydrolysis studies under acidic conditions showed a marked increase in stability with respect to the acid-catalyzed cleavage of the glycosyl bond. Phosphotriesters 9 and 10 exhibited antiviral

  抗病毒嘌呤双脱氧核苷类似物2'，3'-双脱氧腺苷（ddA）（2）和报道了2′，3′-二脱氧-2′，3′-二氢腺苷（d4A）（3）。这些潜在的前核苷酸通过受控的化学诱导的串联反应选择性地释放ddAMP（7）或d4AMP（8）。使用我们先前报道的磷（III）方法，从取代的水杨醇14a-h开始以高收率合成所有新化合物9和10a-d。相对于在磷中心的构型，以立体化学优选为2：1获得了磷酸三酯9和10。在1-辛醇/水混合物中，磷酸三酯9和10的亲脂性比其亲本核苷ddA（2）和d4A（3）高出7-43倍，这可通过它们的log P值来判断。在水解研究中，9和10在温和的碱性水溶液中分解，仅释放ddAMP（7）和d4AMP（8）以及二醇14。进一步的水解研究表明，在酸性条件下，相对于酸-稳定性显着提高。催化的糖基键裂解。磷酸三酸酯9和10对人T淋巴细胞（CEM / O）细胞中的野生型HIV-1和HIV-2
• Phosphoramidite Chemistry for the Synthesis of<i>cyclo</i>Sal-Pro-Nucleotides
  作者：Florence Mugnier、Chris Meier

  DOI：10.1080/15257779908041605

  日期：1999.4

  An alternative synthesis of 3-methyl-cycloSal-nucleotides 3-6 using phosphor amidite chemistry is described. This protocol clearly shows advantages for the cycloSal-introduction into cytosine containing nucleoside analogues.
• <i>N,O</i>-Selectivity in the Synthesis of 3-Me-<i>Cyclo</i>Sal-ddAMP
  作者：Tina Knispel、Chris Meier

  DOI：10.1080/15257779908041607

  日期：1999.4

  The factors influencing the N,O-regioselectivity during preparation of 3-Me-cycloSal-ddAMP were studied.
• Interaction of <i>cyclo</i>Sal-Pronucleotides with Cholinesterases from Different Origins. A Structure−Activity Relationship
  作者：Chris Meier、Christian Ducho、Ulf Görbig、Robert Esnouf、Jan Balzarini

  DOI：10.1021/jm031032a

  日期：2004.5.1

  A large number of cycloSal-nucleotide triesters 1-49 have been studied concerning their ability to inhibit cholinesterases of different origins as well as to inhibit HIV replication in cell culture. It was shown that none of the triesters showed inhibitory effects against human acetylcholinesterase (AChE; isolated enzyme) as well as against AChE from beef erythrocytes and calf serum. In contrast, inhibition of butyrylcholinesterase (BChE) has been observed for some triesters in human and mouse serum. cycloSal pronucleotides showed strong competitive inhibition with respect to the substrate acetylcholine chloride (K-i/K-m: similar to2 x 10(-5)) and acted by time-dependent irreversible inhibition of the human serum BChE. Detailed studies demonstrated that the inhibitory effect against BChE is dependent on the nucleoside analogue, the substitution pattern of the cycloSal-moiety, and particularly on the stereochemistry at the phosphorus atom. Structural requirements to avoid the inhibition of BChE by cycloSal-nucleotide triesters have been elucidated in the reported study.