[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-(2,6-dichloropurin-9-yl)oxolan-2-yl]methoxy-tert-butyl-dimethylsilane | 195727-22-1

• 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: [(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-(2,6-dichloropurin-9-yl)oxolan-2-yl]methoxy-tert-butyl-dimethylsilane
• CAS: 195727-22-1
• 化学式: C₂₈H₅₂Cl₂N₄O₄Si₃
• 分子量: 663.908
• InChiKey: WAFOAMUHVVXWFF-UMCMBGNQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.83
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  80.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-(2,6-dichloropurin-9-yl)oxolan-2-yl]methoxy-tert-butyl-dimethylsilane 在 氟化铵 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 叔丁醇 为溶剂， 生成 2-chloro-N⁶-(2S-endo-norborn-2-yl)adenosine
  参考文献：
  名称：

  新的2，N6-二取代的腺苷：有效和选择性的A1腺苷受体激动剂。

  摘要：

  合成了许多在2和N6-位取代的腺苷类似物，并评估了对A1和A2A腺苷受体（AR）的亲和力，功能效能和内在活性。测试了三类N6-取代基；降冰片-2-基（系列1），降冰片-2-基（系列2）和5,6-环氧降冰片-2-基（系列3）。卤素；氟，溴和碘被评估为C-2取代基。所有化合物对仓鼠平滑肌DDT1 MF-2细胞的A1AR亲和力（纳米摩尔）相对较高，并且抑制（-）异丙肾上腺素刺激的cAMP蓄积的能力较高，每个系列中的2-氟衍生物均具有最高亲和力。所有衍生物均显示出与CPA相同的固有活性。在A2AAR，所有这些衍生物对于刺激大鼠嗜铬细胞瘤PC-12细胞中的cAMP积累均显示出较低的亲和力和效价（微摩尔）。与CGS 21680相比，衍生物的固有活性取决于C-2位的卤素取代基，其中大部分表现出部分激动剂活性。特别令人感兴趣的是2-碘-N6-（2S-内-降冰片-2-基）腺苷（5e），对A1AR的选择性超过

  DOI：

  10.1016/s0968-0896(01)00384-4
• 作为产物：
  描述：

  6-氯嘌呤核苷 在 咪唑 、 N-氯代丁二酰亚胺 、 三丁基氯化锡 、 2,2,6,6-tetramethylpiperidinyl-lithium 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 38.58h， 生成 [(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-(2,6-dichloropurin-9-yl)oxolan-2-yl]methoxy-tert-butyl-dimethylsilane
  参考文献：
  名称：

  A New Entry to 2-Substituted Purine Nucleosides Based on Lithiation-Mediated Stannyl Transfer of 6-Chloropurine Nucleosides

  摘要：

  In spite of exclusive lithiation at the 8-position of 9-(2,3,5-tris-O-TBDMS-beta-D-ribofuranosyl)-6-chloropurine (2) with LDA, subsequent quenching of its lithiated species with Bu3SnCl (or TMSCl) results in the formation of 2-substituted products. Under optimized reaction conditions, where LTMP was us ed as a lithiating agent, 9-(2,3,5-tris-O-TBDMS-beta-D-ribofuranosyl)-6-chloro-2-(tributylstannyl)purine (11) was formed in quantitative yield. Several experiments carried out to verify the reaction mechanism suggested that an anionic stannyl (or silyl) transfer from the 8- to the 2-position had been involved. Manipulation of the 2-tributylstannyl group in 11 and in its adenine counterpart (22) has disclosed a new entry to 2-substituted purine nucleosides. This chemistry was briefly applied to the synthesis of the 2-fluoro analogue of neplanocin A.

  DOI：

  10.1021/jo970398q

文献信息

• A New Entry to 2-Substituted Purine Nucleosides Based on Lithiation-Mediated Stannyl Transfer of 6-Chloropurine Nucleosides
  作者：Keisuke Kato、Hiroyuki Hayakawa、Hiromichi Tanaka、Hiroki Kumamoto、Satoru Shindoh、Satoshi Shuto、Tadashi Miyasaka

  DOI：10.1021/jo970398q

  日期：1997.10.1

  In spite of exclusive lithiation at the 8-position of 9-(2,3,5-tris-O-TBDMS-beta-D-ribofuranosyl)-6-chloropurine (2) with LDA, subsequent quenching of its lithiated species with Bu3SnCl (or TMSCl) results in the formation of 2-substituted products. Under optimized reaction conditions, where LTMP was us ed as a lithiating agent, 9-(2,3,5-tris-O-TBDMS-beta-D-ribofuranosyl)-6-chloro-2-(tributylstannyl)purine (11) was formed in quantitative yield. Several experiments carried out to verify the reaction mechanism suggested that an anionic stannyl (or silyl) transfer from the 8- to the 2-position had been involved. Manipulation of the 2-tributylstannyl group in 11 and in its adenine counterpart (22) has disclosed a new entry to 2-substituted purine nucleosides. This chemistry was briefly applied to the synthesis of the 2-fluoro analogue of neplanocin A.
• New 2,N6-Disubstituted adenosines: potent and selective A1 adenosine receptor agonists
  作者：Sally A Hutchinson、Stephen P Baker、Peter J Scammells

  DOI：10.1016/s0968-0896(01)00384-4

  日期：2002.4

  A number of adenosine analogues substituted in the 2- and N6-positions were synthesized and evaluated for affinity, functional potency and intrinsic activity at the A1 and A2A adenosine receptors (AR). Three classes of N6-substituents were tested; norbornen-2-yl (series 1), norborn-2-yl (series 2) and 5,6-epoxynorborn-2-yl (series 3). The halogens; fluoro, bromo, and iodo were evaluated as C-2 substituents

  合成了许多在2和N6-位取代的腺苷类似物，并评估了对A1和A2A腺苷受体（AR）的亲和力，功能效能和内在活性。测试了三类N6-取代基；降冰片-2-基（系列1），降冰片-2-基（系列2）和5,6-环氧降冰片-2-基（系列3）。卤素；氟，溴和碘被评估为C-2取代基。所有化合物对仓鼠平滑肌DDT1 MF-2细胞的A1AR亲和力（纳米摩尔）相对较高，并且抑制（-）异丙肾上腺素刺激的cAMP蓄积的能力较高，每个系列中的2-氟衍生物均具有最高亲和力。所有衍生物均显示出与CPA相同的固有活性。在A2AAR，所有这些衍生物对于刺激大鼠嗜铬细胞瘤PC-12细胞中的cAMP积累均显示出较低的亲和力和效价（微摩尔）。与CGS 21680相比，衍生物的固有活性取决于C-2位的卤素取代基，其中大部分表现出部分激动剂活性。特别令人感兴趣的是2-碘-N6-（2S-内-降冰片-2-基）腺苷（5e），对A1AR的选择性超过