carbovir monophosphate | 129895-88-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: carbovir monophosphate
• 英文别名: carbovir 5'-phosphate；(-)-Carbovir 5'-monophosphate；[(1S,4R)-4-(2-amino-6-oxo-1H-purin-9-yl)cyclopent-2-en-1-yl]methyl dihydrogen phosphate
• CAS: 129895-88-1
• 化学式: C₁₁H₁₄N₅O₅P
• 分子量: 327.236
• InChiKey: OJDRNVIJFVCXOM-RQJHMYQMSA-N

物化性质

• 溶解度：
  可溶于水

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  152
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  carbovir monophosphate 在 N,N'-二环己基碳二亚胺 作用下， 反应 4.0h， 生成 Triphosphoric acid, mono[[(1S,4R)-4-(2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)-2-cyclopenten-1-yl]methyl] ester
  参考文献：
  名称：

  Synthesis from (–)-aristeromycin and X-ray structure of (–)-carbovir

  摘要：

  Efficient processes are described for the synthesis of (-)-carbovir 3 and its triphosphate derivative 28 from (-)-aristeromycin 4. The X-ray structure of (-)-carbovir has been determined.

  DOI：

  10.1039/p19910002467
• 作为产物：
  描述：

  (1R,4S)-2-Amino-1,9-dihydro-9-<4-(hydroxymethyl)cyclopent-2-enyl>purin-6-one Phosphate 以 水 为溶剂， 以73%的产率得到carbovir monophosphate
  参考文献：
  名称：

  Synthesis from (–)-aristeromycin and X-ray structure of (–)-carbovir

  摘要：

  Efficient processes are described for the synthesis of (-)-carbovir 3 and its triphosphate derivative 28 from (-)-aristeromycin 4. The X-ray structure of (-)-carbovir has been determined.

  DOI：

  10.1039/p19910002467

文献信息

• Human N6-Methyl-AMP/DAMP Aminohydrolase (Abacavir 5'-Monophosphate Deaminase) is Capable of Metabolizing N6-Substituted Purine Acyclic Nucleoside Phosphonates
  作者：Markéta Schinkmanová、Ivan Votruba、Riri Shibata、Bin Han、Xiaohong Liu、Tomas Cihlar、Antonín Holý

  DOI：10.1135/cccc20080275

  日期：——

  Recombinant human abacavir monophosphate deaminase (hABC-MP deaminase) was compared with the recently described ratN⁶-methyl-AMP (meAMP) aminohydrolase. hABC-MP deaminase, a 42 kDa polypeptide, exists predominantly as a monomer under non-denaturing conditions. Similar to the rat enzyme, hABC-MP deaminase efficiently catalyzes the hydrolytic deamination of natural substrates meAMP (5),N⁶,N⁶-dimethyl-AMP (13) and medAMP (6). Acyclic nucleoside phosphonate (ANP)N⁶-cyclopropyl-2,6-diamino-9-[2-(phosphonomethoxy)ethyl]purine (cPrPMEDAP) (1), an intermediate intracellular metabolite of antileukemic agent GS-9219, was effectively converted to the corresponding active guanine analog by hABC-MP deaminase. In addition to cPrPMEDAP (1), a number of other biologically activeN⁶-substituted purine ANPs are alternative substrates for hABC-MP deaminase. The efficiency of their deamination depends on the character ofN⁶-substitution in the adenine and/or 2,6-diaminopurine ring. ANPs withN⁶-cyclic substituents are deaminated more readily than corresponding compounds with aliphatic substituents of the same length. The deamination of ANPs is also influenced by modifications at the phosphonoalkyl side chain. Among 9-[2-(phosphonomethoxy)propyl] ANPs, (S)-enantiomers are preferred to (R)-enantiomers. Alternatively, the presence of extended 9-[2-(phosphonoethoxy)ethyl] moiety leads to a moderate increase in the reaction velocity compared to cPrPMEDAP (1). Comparison of hABC-MP deaminase and the rat meAMP aminohydrolase across a broad spectrum ofN⁶-substituted substrates revealed a strong correlation of their substrate specificities. Similar to the rat meAMP aminohydrolase, hABC-MP deaminase was highly sensitive to deoxycoformycin monophosphate, but not to the guanine product of cPrPMEDAP (1) deamination. Together, these data demonstrate that hABC-MP deaminase is human meAMP aminohydrolase involved in the intracellular activation of biologically activeN⁶-substituted nucleotide analogs.

  重组人阿巴卡韦单磷酸脱氨酶（hABC-MP deaminase）与最近描述的大鼠N6-甲基-AMP（meAMP）氨水解酶进行了比较。在非变性条件下，重组的hABC-MP deaminase是一个42 kDa的多肽，主要存在于单体形式。与大鼠酶类似，hABC-MP deaminase有效催化天然底物meAMP（5）、N6，N6-二甲基-AMP（13）和medAMP（6）的水解脱氨作用。抗白血病药物GS-9219的中间细胞内代谢产物脱环丙基-2,6-二氨基-9-[2-(磷酸甲氧基)乙基]嘌呤（cPrPMEDAP）（1）被hABC-MP deaminase有效地转化为相应的活性鸟嘌呤类似物。除了cPrPMEDAP（1）之外，许多其他生物活性的N6-取代嘌呤ANPs也是hABC-MP deaminase的替代底物。它们的脱氨效率取决于腺嘌呤和/或2,6-二氨基嘌呤环中N6-取代的性质。具有N6-环状取代基的ANPs比相同长度的脂肪取代基的相应化合物更容易脱氨。ANPs的脱氨也受到磷酸烷基侧链修饰的影响。在9-[2-(磷酸甲氧基)丙基] ANPs中，（S）-对映体比（R）-对映体更受欢迎。或者，存在扩展的9-[2-(磷酸乙氧基)乙基]基团会使反应速率与cPrPMEDAP（1）相比有适度的增加。在广泛的N6-取代底物上比较hABC-MP deaminase和大鼠meAMP氨水解酶，发现它们的底物特异性强相关。与大鼠meAMP氨水解酶类似，hABC-MP deaminase对脱氧可酶霉素单磷酸具有高度敏感性，但对cPrPMEDAP（1）脱氨产物的鸟嘌呤没有敏感性。这些数据表明，hABC-MP deaminase是人类meAMP氨水解酶，参与了生物活性N6-取代核苷酸类似物的细胞内激活。
• Synthesis from (–)-aristeromycin and X-ray structure of (–)-carbovir
  作者：Anne M. Exall、Martin F. Jones、Chi-Leung Mo、Peter L. Myers、Ian L. Paternoster、Hardev Singh、Richard Storer、Gordon G. Weingarten、Christopher Williamson、Alastair C. Brodie、John Cook、David E. Lake、Clive A. Meerholz、Peter J. Turnbull、Rona M. Highcock

  DOI：10.1039/p19910002467

  日期：——

  Efficient processes are described for the synthesis of (-)-carbovir 3 and its triphosphate derivative 28 from (-)-aristeromycin 4. The X-ray structure of (-)-carbovir has been determined.