2',3'-O-isopropylideneadenosine-5'-carboxylic acid methyl ester | 23754-29-2

• 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-isopropylideneadenosine-5'-carboxylic acid methyl ester
• 英文别名: methyl 2',3'-O-isopropylideneadenosine-5'-carboxylate；methyl 2',3'-isopropylideneadenosine-5'-carboxylate；1-(6-amino-purin-9-yl)-O²,O³-isopropylidene-β-D-1-deoxy-ribofuranuronic acid methyl ester；2',3'-Isopropyliden-adenosin-5'-carbonsaeuremethylester；methyl (3aR,4R,6S,6aS)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylate
• CAS: 23754-29-2
• 化学式: C₁₄H₁₇N₅O₅
• 分子量: 335.319
• InChiKey: UFOCTAMSMHFCIX-KIKITERTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylideneadenosine-5'-carboxylic acid methyl ester 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 8.0h， 生成 5'-N-甲基甲酰氨基腺苷
  参考文献：
  名称：

  Inactivation of S-Adenosyl-l-homocysteine Hydrolase by Amide and Ester Derivatives of Adenosine-5‘-carboxylic Acid

  摘要：

  S-Adenosyl-L-homocysteine (AdoHcy) hydrolase has been shown to have (5'/6') hydrolytic activity with vinyl (5') or homovinyl (6') halides derived from adenosine (Ado). This hydrolytic activity is independent of its 3'-oxidative activity. The vinyl (or homovinyl) halides are converted into 5'(or 6')-carboxaldehydes by the hydrolytic activity of the enzyme, and inactivation occurs via the oxidative activity. Amide and ester derivatives of Ado-5'-carboxylic acid were prepared to further probe the hydrolytic capability of AdoHcy hydrolase. The oxidative activity (but not the hydrolytic activity) is involved in the mechanism of inhibition of the enzyme by the ester and amide derivatives of Ado-5'-carboxylic acid, in contrast to the inactivation of this enzyme by adenosine-derived vinyl or homovinyl halide analogues during which both activities are manifested.

  DOI：

  10.1021/jm960313y
• 作为产物：
  描述：

  2',3'-异丙叉腺苷 在 氯化亚砜 、 2,2,6,6-四甲基哌啶氧化物 、 碘苯二乙酸 作用下， 以 甲醇 为溶剂， 生成 2',3'-O-isopropylideneadenosine-5'-carboxylic acid methyl ester
  参考文献：
  名称：

  自由基 S-腺苷甲硫氨酸酶 DesII 与 TDP-D-岩藻糖的机理研究

  摘要：

  DesII 是一种自由基S-腺苷甲硫氨酸 (SAM) 酶，可通过 C3 自由基中间体催化 TDP-4-氨基-4,6-二脱氧葡萄糖的 C4 脱氨基作用。然而，如果 C4 氨基被羟基取代（得到 TDP-奎诺糖），C3 上的羟基会被氧化成酮，而不会发生 C4 脱水。据推测，C4 C - N/O 键和自由基中间体 C3 处部分填充的 p 轨道之间的超共轭调节了消除与脱氢竞争的程度。为了研究这一假设，我们检查了 DesII 与 TDP-奎诺糖 (TDP-岩藻糖) C4-差向异构体的反应。该反应主要导致 TDP-6-脱氧古洛糖的形成，并可能导致 TDP-岩藻糖的再生。底物自由基的其余部分在 C3-脱氢和 C4-脱水之间大致相等地分配。因此，改变 C4 的立体化学可以实现消除和脱氢之间更平衡的竞争。

  DOI：

  10.1002/anie.201409540

文献信息

• Avoiding Antibiotic Inactivation in <i>Mycobacterium tuberculosis</i> by Rv3406 through Strategic Nucleoside Modification
  作者：Matthew R. Bockman、Curtis A. Engelhart、Surendra Dawadi、Peter Larson、Divya Tiwari、David M. Ferguson、Dirk Schnappinger、Courtney C. Aldrich

  DOI：10.1021/acsinfecdis.8b00038

  日期：2018.7.13

  5′-[N-(d-biotinoyl)sulfamoyl]amino-5′-deoxyadenosine (Bio-AMS, 1) possesses selective activity against Mycobacterium tuberculosis (Mtb) and arrests fatty acid and lipid biosynthesis through inhibition of the Mycobacterium tuberculosis biotin protein ligase (MtBPL). Mtb develops spontaneous resistance to 1 with a frequency of at least 1 × 10–7 by overexpression of Rv3406, a type II sulfatase that enzymatically

  5'-[ N-（d-生物氨酰基）氨磺酰基]氨基-5'-脱氧腺苷（Bio-AMS，1）具有抗结核分枝杆菌（Mtb）的选择性活性，并通过抑制结核分枝杆菌生物素蛋白而阻止脂肪酸和脂质的生物合成。连接酶（Mt BPL）。Mtb通过过表达Rv3406（一种酶使1失活的II型硫酸酯酶），以至少1×10 –7的频率对1产生自发抗性。。为了避免这种抗性机制，我们在本文中描述了在5'-位置对核苷进行策略性修饰以防止酶促失活。新类似物保留亚纳摩尔效力山BPL（ķ d = 0.66-0.97纳米），和5' - [R - c ^ -甲基衍生物6显示出相同的抗分支杆菌活性的朝向：Mtb的分枝杆菌H37Rv，山BPL过表达，和同基因Rv3406过表达菌株（最小抑制浓度，MIC = 1.56μM）。此外，重组Rv3406不能代谢6个，并且不能分离出对6个有抗性的突变体（抗性频率<1.4×10–10）证明它成功克服了Rv3406介导的抗性。
• Structure-Activity Relationships of N6-Benzyladenosine-5'-uronamides as A3-Selective Adenosine Agonists
  作者：Carola Gallo-Rodriguez、Xiao-duo Ji、Neli Melman、Barry D. Siegman、Lawrence H. Sanders、Jeraldine Orlina、Bilha Fischer、Quanlong Pu、Mark E. Olah

  DOI：10.1021/jm00031a014

  日期：1994.3

  Adenosine analogues modified at the 5'-position as uronamides and/or as N-6-benzyl derivatives were synthesized. These derivatives were examined for affinity in radioligand binding assays at the newly discovered rat brain A(3) adenosine receptor and at rat brain A(1) and Az, receptors. 5'Uronamide substituents favored AS selectivity in the order N-methyl > N-ethyl approximate to unsubstituted carboxamide > N-cyclopropyl. 5'-(N-Methylcarboxamido)-N-6-benzyladenosine was 37-56-fold more selective for Ag receptors. Potency at A(3) receptors was enhanced upon substitution of the benzyl substituent with nitro and other groups. 5'-N-Methyluronamides and N-6-(3-substituted-benzyl) adenosines are optimal for potency and selectivity at A(3) receptors. A series of 3-(halobenzyl)5'-N-ethyluronamide derivatives showed the order of potency at A(1) and A(2)a receptors of I similar to Br > Cl > F. At A(3) receptors the 3-F derivative was weaker than the other halo derivatives. 5'-N-Methyl-N-6- (3-iodobenzyl) adenosine displayed a K-i value of 1.1 nM at A(3) receptors and selectivity versus A(1) and A(2a), receptors of 50-fold. A series of methoxybenzyl derivatives showed that a C-methoxy group best favored A(3) selectivity. A 4-sulfobenzyl derivative was a specific ligand at A(3) receptors of moderate potency. An aryl amino derivative was prepared as a probe for radioiodination and receptor cross-linking.
• Inactivation of <i>S-</i>Adenosyl-<scp>l</scp>-homocysteine Hydrolase by Amide and Ester Derivatives of Adenosine-5‘-carboxylic Acid
  作者：Stanislaw F. Wnuk、Siming Liu、Chong-Sheng Yuan、Ronald T. Borchardt、Morris J. Robins

  DOI：10.1021/jm960313y

  日期：1996.1.1

  S-Adenosyl-L-homocysteine (AdoHcy) hydrolase has been shown to have (5'/6') hydrolytic activity with vinyl (5') or homovinyl (6') halides derived from adenosine (Ado). This hydrolytic activity is independent of its 3'-oxidative activity. The vinyl (or homovinyl) halides are converted into 5'(or 6')-carboxaldehydes by the hydrolytic activity of the enzyme, and inactivation occurs via the oxidative activity. Amide and ester derivatives of Ado-5'-carboxylic acid were prepared to further probe the hydrolytic capability of AdoHcy hydrolase. The oxidative activity (but not the hydrolytic activity) is involved in the mechanism of inhibition of the enzyme by the ester and amide derivatives of Ado-5'-carboxylic acid, in contrast to the inactivation of this enzyme by adenosine-derived vinyl or homovinyl halide analogues during which both activities are manifested.
• Mechanistic Studies of the Radical<i>S</i>-Adenosylmethionine Enzyme DesII with TDP-<scp>D</scp>-Fucose
  作者：Yeonjin Ko、Mark W. Ruszczycky、Sei-Hyun Choi、Hung-wen Liu

  DOI：10.1002/anie.201409540

  日期：2015.1.12

  DesII is a radical S‐adenosylmethionine (SAM) enzyme that catalyzes the C4‐deamination of TDP‐4‐amino‐4,6‐dideoxyglucose through a C3 radical intermediate. However, if the C4 amino group is replaced with a hydroxy group (to give TDP‐quinovose), the hydroxy group at C3 is oxidized to a ketone with no C4‐dehydration. It is hypothesized that hyperconjugation between the C4 CN/O bond and the partially

  DesII 是一种自由基S-腺苷甲硫氨酸 (SAM) 酶，可通过 C3 自由基中间体催化 TDP-4-氨基-4,6-二脱氧葡萄糖的 C4 脱氨基作用。然而，如果 C4 氨基被羟基取代（得到 TDP-奎诺糖），C3 上的羟基会被氧化成酮，而不会发生 C4 脱水。据推测，C4 C - N/O 键和自由基中间体 C3 处部分填充的 p 轨道之间的超共轭调节了消除与脱氢竞争的程度。为了研究这一假设，我们检查了 DesII 与 TDP-奎诺糖 (TDP-岩藻糖) C4-差向异构体的反应。该反应主要导致 TDP-6-脱氧古洛糖的形成，并可能导致 TDP-岩藻糖的再生。底物自由基的其余部分在 C3-脱氢和 C4-脱水之间大致相等地分配。因此，改变 C4 的立体化学可以实现消除和脱氢之间更平衡的竞争。