[(2S,3R,5S)-2-acetyloxy-5-(methylcarbamoyl)oxolan-3-yl] acetate | 163042-98-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(2S,3R,5S)-2-acetyloxy-5-(methylcarbamoyl)oxolan-3-yl] acetate
• CAS: 163042-98-6
• 化学式: C₁₀H₁₅NO₆
• 分子量: 245.232
• InChiKey: XRDXWROWLAVWOH-QXFUBDJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-Chloro-N-(3-iodobenzyl)-9-(trimethylsilyl)-9H-purin-6-amine 、 [(2S,3R,5S)-2-acetyloxy-5-(methylcarbamoyl)oxolan-3-yl] acetate 在 三氟甲磺酸三甲基硅酯 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 17.0h， 生成 9-<2-acetyl-3-deoxy-5-(methylcarbamoyl)-β-D-ribofuranosyl>-2-chloro-N⁶-(3-iodobenzyl)adenine
  参考文献：
  名称：

  Structure-Activity Relationships of 9-Alkyladenine and Ribose-Modified Adenosine Derivatives at Rat A3 Adenosine Receptors

  摘要：

  9-Alkyladenine derivatives and ribose-modified N-6-benzyladenosine derivatives were synthesized in an effort to identify selective ligands for the rat A(3) adenosine receptor and leads for the development of antagonists. The derivatives contained structural features previously determined to be important for A(3) selectivity in adenosine derivatives, such as an N-6-(3-iodobenzyl) moiety, and were further substituted at the 2-position with halo, amino, or thio groups. Affinity was determined in radioligand binding assays at rat brain A(3) receptors stably expressed in Chinese hamster ovary (CHO) cells, using [I-125]]AB-MECA (N-6-(4-amino-3-iodobenzyl)adenosine-5'-(N-methyluronamid)), and at rat brain A(1) and A(2a) receptors using [H-3]-N-6-PIA ((R)-N-6-phenylisopropyladenosine) and [H-3]CGS 21680 (2-[[[4-(2-carboxyethyl)-phenyl]ethyl]amino]-5'-(N-ethylcarbamoyl)adenosine), respectively. A series of N-6-(3-iodobenzyl) 2-amino derivatives indicated that a small 2-alkylamino group, e.g., methylamino, was favored at A(3) receptors. N-6-(3-Iodobenzyl)-9-methyl-2-(methylthio)adenine was 61-fold more potent than the corresponding 2-methoxy ether at A(3) receptors and of comparable affinity at A(1) and A(2a) receptors, resulting in a 3-6-fold selectivity for A(3) receptors. A pair of chiral N-6-(3-iodobenzyl) 9-(2,3-dihydroxypropyl) derivatives showed stereoselectivity, with the R-enantiomer favored at A(3) receptors by 5.7-fold. 2-Chloro-9-(beta-D-erythrofuranosyl)-N-6-(3-iodobenzyl)adenine had a K-i value at A(3) receptors of 0.28 mu M. 2-Chloro-9-[2-amino-2,3-dideoxy-beta-D-5-(methylcarbamoyl)-arabinofuranosyl]-N-6-(3-iodobenzyl)adenine was moderately selective for A(1) and A(3) VS A(2a) receptors. A 3'-deoxy analogue of a highly A(3)-selective adenosine derivative retained selectivity in binding and was a full agonist in the inhibition of adenylyl cyclase mediated via cloned rat A(3) receptors expressed in CHO cells. The 3'-OH and 4'-CH2OH groups of adenosine are not required for activation at A(3) receptors. A number of 2',3'-dideoxyadenosines and 9-acyclic-substituted adenines appear to inhibit adenylyl cyclase at the allosteric ''P'' site.

  DOI：

  10.1021/jm00010a017
• 作为产物：
  描述：

  乙酸酐 、 methyl 3-deoxy-1,2-isopropylidene-α-D-ribofuronamide 在 硫酸 作用下， 以 溶剂黄146 为溶剂， 反应 18.0h， 以80%的产率得到[(2S,3R,5S)-2-acetyloxy-5-(methylcarbamoyl)oxolan-3-yl] acetate
  参考文献：
  名称：

  Structure-Activity Relationships of 9-Alkyladenine and Ribose-Modified Adenosine Derivatives at Rat A3 Adenosine Receptors

  摘要：

  9-Alkyladenine derivatives and ribose-modified N-6-benzyladenosine derivatives were synthesized in an effort to identify selective ligands for the rat A(3) adenosine receptor and leads for the development of antagonists. The derivatives contained structural features previously determined to be important for A(3) selectivity in adenosine derivatives, such as an N-6-(3-iodobenzyl) moiety, and were further substituted at the 2-position with halo, amino, or thio groups. Affinity was determined in radioligand binding assays at rat brain A(3) receptors stably expressed in Chinese hamster ovary (CHO) cells, using [I-125]]AB-MECA (N-6-(4-amino-3-iodobenzyl)adenosine-5'-(N-methyluronamid)), and at rat brain A(1) and A(2a) receptors using [H-3]-N-6-PIA ((R)-N-6-phenylisopropyladenosine) and [H-3]CGS 21680 (2-[[[4-(2-carboxyethyl)-phenyl]ethyl]amino]-5'-(N-ethylcarbamoyl)adenosine), respectively. A series of N-6-(3-iodobenzyl) 2-amino derivatives indicated that a small 2-alkylamino group, e.g., methylamino, was favored at A(3) receptors. N-6-(3-Iodobenzyl)-9-methyl-2-(methylthio)adenine was 61-fold more potent than the corresponding 2-methoxy ether at A(3) receptors and of comparable affinity at A(1) and A(2a) receptors, resulting in a 3-6-fold selectivity for A(3) receptors. A pair of chiral N-6-(3-iodobenzyl) 9-(2,3-dihydroxypropyl) derivatives showed stereoselectivity, with the R-enantiomer favored at A(3) receptors by 5.7-fold. 2-Chloro-9-(beta-D-erythrofuranosyl)-N-6-(3-iodobenzyl)adenine had a K-i value at A(3) receptors of 0.28 mu M. 2-Chloro-9-[2-amino-2,3-dideoxy-beta-D-5-(methylcarbamoyl)-arabinofuranosyl]-N-6-(3-iodobenzyl)adenine was moderately selective for A(1) and A(3) VS A(2a) receptors. A 3'-deoxy analogue of a highly A(3)-selective adenosine derivative retained selectivity in binding and was a full agonist in the inhibition of adenylyl cyclase mediated via cloned rat A(3) receptors expressed in CHO cells. The 3'-OH and 4'-CH2OH groups of adenosine are not required for activation at A(3) receptors. A number of 2',3'-dideoxyadenosines and 9-acyclic-substituted adenines appear to inhibit adenylyl cyclase at the allosteric ''P'' site.

  DOI：

  10.1021/jm00010a017

文献信息

• Synthesis of New Nucleosides by coupling of chloropurines with 2- and 3-deoxy derivatives ofN-methyl-D-ribofuranuronamide
  作者：Rosaria Volpini、Emidio Camaioni、Sauro Vittori、Luciano Barboni、Catia Lambertucci、Gloria Cristalli

  DOI：10.1002/hlca.19980810113

  日期：1998.1.12

  The synthesis of new deoxyribose nucleosides by coupling chloropurines with modified D-ribose derivatives is reported. The methyl 2-deoxy-N-methyl-3-O-(p-toluoyl)-α-D-ribofuranosiduronamide (α-D-8) and the corresponding anomer β-D-8 were synthesized starting from the commercially available 2-deoxy-D-ribose (1) (Scheme 1). Reaction of α-D-8 with the silylated derivative of 2,6-dichloro-9H-purine (9)

  报道了通过将氯嘌呤与修饰的D-核糖衍生物偶联来合成新的脱氧核糖核苷。从商购可得的2-开始，合成了甲基2-脱氧-N-甲基-3- O-（对甲苯甲酰基）-α-D-呋喃呋喃基硅二硼酰胺（α-D- 8）和相应的端基异构体β-D- 8。脱氧-D-核糖（1）（方案1）。α-D- 8与2,6-二氯-9 H-嘌呤的甲硅烷基化衍生物（9）反应，选择性地提供N 9-（2'-脱氧核糖核苷）10异头混合物（方案2）），而β-D- 8没有反应。9或6-氯-9 H-嘌呤（17）与1,2-二-O-乙酰基-3-脱氧-N-甲基-β-D-核呋喃核糖酰胺（13）的糖基化仅产生受保护的β-D -端基异构体14和18（方案3）。随后的脱乙酰基和脱氯得到所需的核苷β-D- 11，β-D- 12,15和16。3'-脱氧-2-氯腺苷衍生物15对A的腺苷结合位点显示出最高的亲和力和选择性1和A 2A腺苷受体亚型。