9-[(1S,3S,4S)-3,4-Bis(hydroxymethyl)-cyclohexyl]-guanine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 9-[(1S,3S,4S)-3,4-Bis(hydroxymethyl)-cyclohexyl]-guanine
• 英文别名: 9-[(1S,3S,4S)-3,4-bis(hydroxymethyl)cyclohexyl]-guanine；2-amino-9-[(1S,3S,4S)-3,4-bis(hydroxymethyl)cyclohexyl]-1H-purin-6-one
• 化学式: C₁₃H₁₉N₅O₃
• 分子量: 293.326
• InChiKey: SNCFJLSVMLYJNX-HLTSFMKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  rac-trans-4,5-bis(methoxycarbonyl)cyclohexene 在 palladium on activated charcoal 吡啶 、 盐酸 、 sodium hydroxide 、 lithium aluminium tetrahydride 、 DIAD 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 间氯过氧苯甲酸 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 107.0h， 生成 9-[(1S,3S,4S)-3,4-Bis(hydroxymethyl)-cyclohexyl]-guanine
  参考文献：
  名称：

  Synthesis of Enantiomerically Pure Bis(hydroxymethyl)-Branched Cyclohexenyl and Cyclohexyl Purines as Potential Inhibitors of HIV

  摘要：

  The synthesis of the enantiomerically pure bis(hydroxymethyl)-branched cyclohexenyl and cyclohexyl purines is described. Racemic trans-4,5-bis(methoxycarbonyl)cyclohexene [(+/-)-6] was reduced with lithium aluminum hydride to give the racemic diol (+/-)-7. Resolution of(+/-)-7 via a transesterification process using lipase from Pseudomonas sp. (SAM-II) gave both diols in enantiomerically pure form. The enantiomerically pure diol (S,S)-7 was benzoylated and epoxidized to give the epoxide 9. Treatment of the epoxide 9 with trimethylsilyl trifluoromethanesulfonate and 1,5-diazabicyclo-[5.4.0]undec-5-ene followed by dilute hydrochloric acid gave (LR,4S,5R)-4,5-bis[(benzoyloxy)methyl]-1-hydroxycyclohex-2-ene (10). Acetylation of 10 gave (LR,4S,5R)-1-acetoxy-4,5-bis[(benzoyloxy)-methyl]cyclohex-2-ene (11). (1R,4S,5R)-1-Acetoxy-4,5-bis[(benzoyloxy)methyl]cyclohex-2-ene (11) was converted to the adenine derivative 12 and guanine derivative 13 via palladium(0)-catalyzed coupling with adenine and 2-amino-6-chloropurine, respectively. Hydrogenation of 12 and 13 gave the correspondning saturated adenine derivative 14 and guanine derivative 15. (1R,4S,5R)-4,5-Bis[(benzoyloxy)methyl]-1-hydroxycyclohex-2-ene (10) was converted to the adenine derivative 16 and guanine derivative 1? via coupling with 6-chloropurine and 2-amino-6-chloropurine, respectively, using a modified Mitsunobu procedure. Hydrogenation of 16 and 17 gave the corresponding saturated adenine derivative 18 and guanine derivative 19. Compounds 12-19 were evaluated for activity against human immunodeficiency virus (HIV), but mere found to be inactive. Further biological testings are underway.

  DOI：

  10.1021/jo9603542

文献信息

• Adenine and guanine derivatives for the treatment of hepatitis virus
  申请人：Nippon Kayaku Kabushiki Kaisha

  公开号：US05374625A1

  公开（公告）日：1994-12-20

  A novel nucleic acid derivative represented by the following general formula (I) and physiologically acceptable salt thereof which are expected to have an antiviral activity: ##STR1## wherein B represents a nucleic acid base derivative; A.sup.1 and A.sup.2 represent, independently of each other, OR.sup.1 or OCOR.sup.1 ; R.sup.1 represents a hydrogen atom, a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group; l represents a number of 0 or 1; and m and n each represents an integer of 0-2; provided that when l and m are 0, n is 0 or 2.

  由以下一般式（I）表示的新型核酸衍生物及其生理上可接受的盐，预计具有抗病毒活性：##STR1## 其中B代表核酸碱基衍生物；A.sup.1和A.sup.2分别表示OR.sup.1或OCOR.sup.1；R.sup.1代表氢原子、取代或未取代的烷基或取代或未取代的芳基；l表示0或1的数字；m和n分别表示0-2的整数；但当l和m为0时，n为0或2。
• Novel nucleic acid derivatives
  申请人：Nippon Kayaku Kabushiki Kaisha

  公开号：EP0468352A2

  公开（公告）日：1992-01-29

  A novel nucleic acid derivative represented by the following general formula (I) and physiologically acceptable salt thereof which are expected to have an antiviral activity: wherein B represents a nucleic acid base derivative; A1 and A2 represent, independently of each other, OR1 or OCOR1; R1 represents a hydrogen atom, a substituted or unsubstituted alkyl group or a substituted or unsubstituted aryl group; ℓ represents a number of 0 or 1; and m and n each represents an integer of 0-2; provided that when ℓ and m are 0, n is 0 or 2.

  由以下通式(I)代表的新型核酸衍生物及其生理上可接受的盐，有望具有抗病毒活性： 其中 B 代表核酸碱基衍生物；A1 和 A2 各自代表 OR1 或 OCOR1；R1 代表氢原子、取代或未取代的烷基或取代或未取代的芳基；ℓ 代表 0 或 1 的数字；m 和 n 各自代表 0-2 的整数；但当 ℓ 和 m 为 0 时，n 为 0 或 2。
• US5374625A
  申请人：——

  公开号：US5374625A

  公开（公告）日：1994-12-20
• Synthesis of Enantiomerically Pure Bis(hydroxymethyl)-Branched Cyclohexenyl and Cyclohexyl Purines as Potential Inhibitors of HIV
  作者：Åsa Rosenquist、Ingemar Kvarnström、Björn Classon、Bertil Samuelsson

  DOI：10.1021/jo9603542

  日期：1996.1.1

  The synthesis of the enantiomerically pure bis(hydroxymethyl)-branched cyclohexenyl and cyclohexyl purines is described. Racemic trans-4,5-bis(methoxycarbonyl)cyclohexene [(+/-)-6] was reduced with lithium aluminum hydride to give the racemic diol (+/-)-7. Resolution of(+/-)-7 via a transesterification process using lipase from Pseudomonas sp. (SAM-II) gave both diols in enantiomerically pure form. The enantiomerically pure diol (S,S)-7 was benzoylated and epoxidized to give the epoxide 9. Treatment of the epoxide 9 with trimethylsilyl trifluoromethanesulfonate and 1,5-diazabicyclo-[5.4.0]undec-5-ene followed by dilute hydrochloric acid gave (LR,4S,5R)-4,5-bis[(benzoyloxy)methyl]-1-hydroxycyclohex-2-ene (10). Acetylation of 10 gave (LR,4S,5R)-1-acetoxy-4,5-bis[(benzoyloxy)-methyl]cyclohex-2-ene (11). (1R,4S,5R)-1-Acetoxy-4,5-bis[(benzoyloxy)methyl]cyclohex-2-ene (11) was converted to the adenine derivative 12 and guanine derivative 13 via palladium(0)-catalyzed coupling with adenine and 2-amino-6-chloropurine, respectively. Hydrogenation of 12 and 13 gave the correspondning saturated adenine derivative 14 and guanine derivative 15. (1R,4S,5R)-4,5-Bis[(benzoyloxy)methyl]-1-hydroxycyclohex-2-ene (10) was converted to the adenine derivative 16 and guanine derivative 1? via coupling with 6-chloropurine and 2-amino-6-chloropurine, respectively, using a modified Mitsunobu procedure. Hydrogenation of 16 and 17 gave the corresponding saturated adenine derivative 18 and guanine derivative 19. Compounds 12-19 were evaluated for activity against human immunodeficiency virus (HIV), but mere found to be inactive. Further biological testings are underway.