5(R)-(6-amino-9H-purin-9-yl)-1(S),2(R)-dihydroxy-3(S)-N-(N-tert-butyloxycarbonylhydroxamino)cyclopentane | 210162-91-7

• 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: 5(R)-(6-amino-9H-purin-9-yl)-1(S),2(R)-dihydroxy-3(S)-N-(N-tert-butyloxycarbonylhydroxamino)cyclopentane
• 英文别名: tert-butyl N-[(1S,2R,3S,4R)-4-(6-aminopurin-9-yl)-2,3-dihydroxycyclopentyl]-N-hydroxycarbamate
• CAS: 210162-91-7
• 化学式: C₁₅H₂₂N₆O₅
• 分子量: 366.377
• InChiKey: GRHUNVARHXWPHZ-YKDSUIRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5(R)-(6-amino-9H-purin-9-yl)-1(S),2(R)-dihydroxy-3(S)-N-(N-tert-butyloxycarbonylhydroxamino)cyclopentane 在 盐酸 作用下， 反应 4.0h， 以47%的产率得到(+/-)-(1'β,2'α,3'α,4'β)-1'-(6-amino-purin-9-yl)-2',3'-(dihydroxy)-4'-(N-hydroxy)amino-cyclopentane
  参考文献：
  名称：

  Synthesis of Novel Carbocyclic Adenosine Analogues as Inhibitors of Adenosine Kinase

  摘要：

  Several new 4'-amino substituted carbocyclic adenosine analogues (6, 7, 31) were prepared as potential inhibitors of the enzyme adenosine kinase. Three different heterocyclic base moieties (adenine, 8-azaadenine, and pyrazolo[3,4-d]pyrimidine) were incorporated into carbocyclic nucleoside analogues through the use of two different synthetic strategies. In both strategies, bicyclic isoxazolidine 9 (prepared through a hetero Diels-Alder reaction with cyclopentadiene) was used as the starting material. In one route, the N-O bond was reductively cleaved, and the hydroxyl group (after inversion and ring functionalization) was used as a leaving group to incorporate the heterocyclic base moiety as the key bond-forming step. A second, more efficient and higher yielding synthetic route was developed as a general solution to the synthesis of the target 4'-amino substituted carbocyclic adenosine analogues. In this methodology, the allylic C-O bond in the bicyclic isoxazolidine 9 was cleaved with double stereoinversion under palladium(0) catalysis as the key bond-forming step to stereospecifically incorporate the heterocyclic base moiety into the cyclopentane ring. The regioselectivity of key bond-forming steps was established principally by NMR methods, especially through (13)C NMR shifts and by NOE effects seen in the analogues, as well as by HMBC/HMQC experiments.

  DOI：

  10.1021/jo981658m
• 作为产物：
  描述：

  2-oxa-3-aza-bicyclo[2.2.1]hept-5-ene-3-carboxylic acid tert-butyl ester 在 咪唑 、 四氧化锇 、 四(三苯基膦)钯 、 氨 、 lithium hydride 、 N-甲基吗啉氧化物 作用下， 以 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 71.0h， 生成 5(R)-(6-amino-9H-purin-9-yl)-1(S),2(R)-dihydroxy-3(S)-N-(N-tert-butyloxycarbonylhydroxamino)cyclopentane
  参考文献：
  名称：

  Synthesis of Novel Carbocyclic Adenosine Analogues as Inhibitors of Adenosine Kinase

  摘要：

  Several new 4'-amino substituted carbocyclic adenosine analogues (6, 7, 31) were prepared as potential inhibitors of the enzyme adenosine kinase. Three different heterocyclic base moieties (adenine, 8-azaadenine, and pyrazolo[3,4-d]pyrimidine) were incorporated into carbocyclic nucleoside analogues through the use of two different synthetic strategies. In both strategies, bicyclic isoxazolidine 9 (prepared through a hetero Diels-Alder reaction with cyclopentadiene) was used as the starting material. In one route, the N-O bond was reductively cleaved, and the hydroxyl group (after inversion and ring functionalization) was used as a leaving group to incorporate the heterocyclic base moiety as the key bond-forming step. A second, more efficient and higher yielding synthetic route was developed as a general solution to the synthesis of the target 4'-amino substituted carbocyclic adenosine analogues. In this methodology, the allylic C-O bond in the bicyclic isoxazolidine 9 was cleaved with double stereoinversion under palladium(0) catalysis as the key bond-forming step to stereospecifically incorporate the heterocyclic base moiety into the cyclopentane ring. The regioselectivity of key bond-forming steps was established principally by NMR methods, especially through (13)C NMR shifts and by NOE effects seen in the analogues, as well as by HMBC/HMQC experiments.

  DOI：

  10.1021/jo981658m

文献信息

• Syntheses of novel hydroxylamine carbanucleosides
  作者：Mark J. Mulvihill、Marvin J. Miller

  DOI：10.1016/s0040-4020(98)00359-7

  日期：1998.6

  Enantiomerically pure 4'-hydroxylamino-adenine-derived carbanucleosides have been synthesized as isosteric 4'-hydroxymethyl analogs to carbovir, ddA, and aristeromycin. The key steps in the syntheses involved an enzymatic desymmetrization, two subsequent Mitsunobu reactions, and a highly diastereoselective ruthenium tetroxide-mediated dihydroxylation, overcoming the syn-directing effect seen in osmium tetroxide-mediated dihydroxylations. Hydroxylamino-propane analogs were also synthesized through similar methodology to afford adenine and cyclopropylamino purine analogs to acyclovir. (C) 1998 Elsevier Science Ltd. All rights reserved.