2',3'-O-isopropylidene-6-methylpurine | 92325-50-3

• 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: 2',3'-O-isopropylidene-6-methylpurine
• 英文别名: 6-methyl-9-(2,3-O-isopropylidene-β-D-ribofuranosyl)purine；O²,O³-isopropylidene-1-(6-methyl-purin-9-yl)-β-D-1-deoxy-ribofuranose；((3aR,4R,6R,6aR)-2,2-Dimethyl-6-(6-methyl-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol；[(3aR,4R,6R,6aR)-2,2-dimethyl-4-(6-methylpurin-9-yl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol
• CAS: 92325-50-3
• 化学式: C₁₄H₁₈N₄O₄
• 分子量: 306.321
• InChiKey: VURWMPLXGDZJHE-UORFTKCHSA-N

物化性质

• 沸点：
  511.2±60.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  91.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylidene-6-methylpurine 在 sodium methylate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 为溶剂， 生成 9-[5-deoxy-5-[[2-(1H-imidazol-4-yl)ethyl]thio]-2,3-O-isopropylidene-β-D-ribofuranosyl]-6-methyl-9H-purine
  参考文献：
  名称：

  SYNTHESIS AND BIOLOGICAL ACTIVITY OF 2-FLUORO ADENINE AND 6-METHYL PURINE NUCLEOSIDE ANALOGS AS PRODRUGS FOR SUICIDE GENE THERAPY OF CANCER

  摘要：

  A novel series of 6-methylpurine nucleoside derivatives with substitutions at 5'-position have been synthesised. These compounds bear a 5'-heterocycle such as triazole or a imidazole with a two carbon chain, and an ether, thio ether or amine. To extend the SAR study of 2-fluoroadenine and 6-methyl purine nucleosides, their corresponding alpha-linker nucleosides with L-xylose and L-lyxose were also synthesized. All of these compounds have been evaluated for their substrate activity with E. coli PNP.

  DOI：

  10.1081/ncn-200059237
• 作为产物：
  描述：

  5'-O-acetyl-2',3'-isopropylidene inosine 在 甲醇 、 sodium methylate 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2',3'-O-isopropylidene-6-methylpurine
  参考文献：
  名称：

  SYNTHESIS AND BIOLOGICAL ACTIVITY OF 2-FLUORO ADENINE AND 6-METHYL PURINE NUCLEOSIDE ANALOGS AS PRODRUGS FOR SUICIDE GENE THERAPY OF CANCER

  摘要：

  A novel series of 6-methylpurine nucleoside derivatives with substitutions at 5'-position have been synthesised. These compounds bear a 5'-heterocycle such as triazole or a imidazole with a two carbon chain, and an ether, thio ether or amine. To extend the SAR study of 2-fluoroadenine and 6-methyl purine nucleosides, their corresponding alpha-linker nucleosides with L-xylose and L-lyxose were also synthesized. All of these compounds have been evaluated for their substrate activity with E. coli PNP.

  DOI：

  10.1081/ncn-200059237

文献信息

• One-Pot Synthesis of Nucleoside 5′-Triphosphates from Nucleoside 5′-<i>H</i>-Phosphonates
  作者：Qi Sun、Jocelyn P. Edathil、Runzhi Wu、Eric D. Smidansky、Craig E. Cameron、Blake R. Peterson

  DOI：10.1021/ol8003029

  日期：2008.5.1

  Nucleoside 5'-triphosphates (NTPs) play key roles in biology and medicine. However, these compounds are notoriously difficult to synthesize. We describe a one-pot method to prepare NTPs from nucleoside 5'-H-phosphonate monoesters via pyridinium phosphoramidates, and we used this approach to synthesize ATP, UTP, GTP, CTP, ribavirin-TP, and 6-methylpurine ribonucleoside-TP (6MePTP). Poliovirus RNA-dependent

  核苷 5'-三磷酸 (NTP) 在生物学和医学中起着关键作用。然而，众所周知，这些化合物难以合成。我们描述了一种通过氨基磷酸吡啶鎓从核苷 5'-H-膦酸酯单酯制备 NTP 的一锅法，我们使用这种方法合成了 ATP、UTP、GTP、CTP、利巴韦林-TP 和 6-甲基嘌呤核糖核苷-TP（ 6MePTP）。脊髓灰质炎病毒 RNA 依赖性 RNA 聚合酶有效地使用 6MePTP 作为底物，这表明同源核苷（一种知之甚少的抗病毒剂）可能会损害病毒 RNA。
• Ribofuranose-ring cleavage of purine nucleosides with diisobutylaluminum hydride: Convenient method for the preparation of purine acyclonucleosides
  作者：Kosaku Hirota、Yasunari Monguchi、Yukio Kitade、Hironao Sajiki

  DOI：10.1016/s0040-4020(97)10098-9

  日期：1997.12

  The reaction of 2′,3′-O-isopropylidene protected purine nucleosides with diisobutylaluminum hydride (DIBAL-H) caused the reductive cleavage of the C-1′O-4′ bond to give the corresponding 9-d-ribitylpurines. The ring cleavage of inosine 1a, thioinosine 1f, and their derivatives having an alkyl group at the O6- or S6-position 1c,e, and g proceeded smoothly to afford the corresponding ribityl derivatives

  2'，3'- O-异亚丙基保护的嘌呤核苷与二异丁基氢化铝（DIBAL-H）的反应引起C-1'O-4'键的还原裂解，得到相应的9-d-核糖尿烷。肌苷1a，硫代肌苷1f及其在O 6或S 6位置1c，e和g具有烷基的衍生物的环裂解顺利进行，得到相应的核糖衍生物2a，f，c，e和g，而N 6-甲基化的腺苷衍生物1k和l显着抵抗了DIBAL-H的还原。5′-脱氧和5′-氯-5′-脱氧衍生物1b，d，i和j也在相似条件下在糖部分进行还原裂解。由鸟苷衍生物5以类似的方式制备了具有生物学意义的鸟苷6的无环类似物。合成嘌呤无环核苷的本方法学也被用于制备奈普兰霉素A的无环类似物17。
• Regioselective Metalation of 6-Methylpurines: Synthesis of Fluoromethyl Purines and Related Nucleosides for Suicide Gene Therapy of Cancer
  作者：Abdalla E. A. Hassan、William B. Parker、Paula W. Allan、John A. Secrist

  DOI：10.1080/15257770903091938

  日期：2009.8.11

  Metalation of 6-methyl-9-(tetrahydro-2H-pyran-2-yl)purine (10) with lithiating agents of varying basicities such as n-BuLi and LiHMDS in THF at - 78 degrees C resulted in metalation at both of the 6-CH3 moiety and the 8-CH position, irrespective of the molar equivalence of the base. On the other hand, a regioselective metalation at the 6-CH3 moiety of 10 was observed with NaHMDS or KHMDS, under similar conditions. Treatment of the potassium salts of 10 and of the protected riboside derivative 6-methyl-9-(beta-D-2,3,5-tri-O-tert-butyldimethylsilylribofuranosyl)purine (22) with N-fluorobenzenesulfonamide (NFSI) at - 78 degrees C gave the corresponding 6-fluoromethylpurine derivatives 11 and 23, respectively, in good yields. Deprotection of 11 and 23 under standard conditions gave 6-fluoromethylpurine (6-FMeP, 3) and 6-fluoromethyl-9-(beta-D-ribofuranosyl)purine (6-FMePR, 4), respectively, in high yield. Both 3 and 4 demonstrated cytotoxic activity against CCRF-CEM cells in culture. 6-FMePR is a good substrate for E. coli purine nucleoside phosphorylase (E. coli PNP) with a comparable substrate activity to that of the parent nucleoside, 6-methyl-9-(beta-D-ribofuranosyl)purine (&MePA 21). The cytotoxic activity of 6-FMeP along with the substrate activity of 6-FMePR with E. coli PNP meet the fundamental requirements for using 6-FMeP as a Potential toxin in PAT/prodrug based cancer gene therapy.
• bis(<i>t</i>BuSATE) PHOSPHOTRIESTER PRODRUGS OF 8-AZAGUANOSINE AND 6-METHYLPURINE RIBOSIDE; bis(POM) PHOSPHOTRIESTER PRODRUGS OF 2′-DEOXY-4′-THIOADENOSINE AND ITS CORRESPONDING 9α ANOMER
  作者：J. D. Rose、W. B. Parker、J. A. Secrist

  DOI：10.1081/ncn-200061889

  日期：2005.4.1

  As an extension of previous work with bis(POM) nucleotide prodrugs, we report the synthesis and biological evaluation in tumor cell culture of the bis(pivaloyloxymethyl) phosphatriester prodrug of slightly cytotoxic 2'-deoxy-4'-thioadenosine and its alpha-anomer. We have experienced need for an alternative phosphate masking group, particularly with purine nucleosides. Accordingly, we report synthesis and biological evaluation of the bis(tBuSATE)phosphotriester prodrugs of 8-azaguanosine and 6-methylpurine riboside, nucleoside analogs with moderate to significant cytotoxicity. All four prodrugs were examined in tumor cell culture in parallel with the parent nucleosides. Synthetic routes and biological data are presented.
• METHOD OF REDUCING INTRAOCULAR PRESSURE IN HUMANS
  申请人：Inotek Pharmaceuticals Corporation

  公开号：US20150080330A1

  公开（公告）日：2015-03-19

  Provided herein is a method of reducing intraocular pressure (IOP) in humans using N6-cyclopentyladenosine (CPA), CPA derivatives or prodrugs or enhanced cornea permeability formulations of CPA. In one embodiment, the invention is directed to CPA derivatives or prodrugs that are permeable to the cornea. In another embodiment, the invention is directed to uses of certain compounds in human subjects for reducing and/or controlling elevated or abnormally fluctuating IOPs in the treatment of glaucoma or ocular hypertension (OHT).