2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate) | 101622-47-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate)
• 英文别名: (2',3'-O-isopropylideneadenosin-5'-yl)methylenebisphosphonate；[[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-hydroxyphosphoryl]methylphosphonic acid
• CAS: 101622-47-3
• 化学式: C₁₄H₂₁N₅O₉P₂
• 分子量: 465.296
• InChiKey: SKOKVWYTLPVTQA-QYVSTXNMSA-N

物化性质

• 沸点：
  796.1±70.0 °C(Predicted)
• 密度：
  2.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  201
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate) 在 吡啶 、 N,N'-二异丙基碳二亚胺 作用下， 反应 20.0h， 生成
  参考文献：
  名称：

  新型麦考酚腺嘌呤双（膦酸酯）类似物可作为对抗人类白血病的潜在分化剂。

  摘要：

  新型霉酚酚腺嘌呤二核苷酸（MAD）类似物已被制备为肌苷单磷酸脱氢酶（IMPDH）的潜在抑制剂。MAD类似物类似于在IMPDH的辅因子结合域上的烟酰胺腺嘌呤二核苷酸结合。然而，它们不能参与氢化物转移，因此抑制了酶。亚甲基双（膦酸酯）类似物C2-MAD和C4-MAD是通过在二异丙基碳二亚胺存在下将2'，3'-O-异丙基亚氨腺苷5'-亚甲基双（膦酸酯）（22）与麦考酚醇20和21偶合而获得的。C2-MAD也可以通过将霉酚酚亚甲基双（膦酸酯）衍生物30与2'，3'-O-异丙基亚氨腺苷偶联来制备。在吉川氏反应条件下，用市售的亚甲基双（二氯化膦）处理苄基保护的霉酚醇27，可以方便地合成化合物30。发现C2-MAD和C4-MAD与霉酚酸（IC（50）= 0.3 microM）一样有效地抑制K562细胞的生长（IC（50）= 0.7 microM和IC（50）= 0.1 microM）。另外，C2-MAD

  DOI：

  10.1021/jm0104116
• 作为产物：
  描述：

  ((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl methanesulfonate 、 (Bu4N)3 OMDP 以 二甲基亚砜 为溶剂， 生成 2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate)
  参考文献：
  名称：

  Efficient Synthesis of Methylenebis(phosphonate) Analogues of P¹,P²-Disubstituted Pyrophosphates of Biological Interest. A Novel Plausible Mechanism

  摘要：

  Synthesis of novel nucleoside bicyclic trisanhydrides 7 in the reaction of nucleoside-5'-methylenebis-(phosphonate)s (4) with DCC is described. They were obtained by P-1,P-3- and P-2,P-3-dehydration of initially formed P-1,P-2,P-3,P-4-bismethylenetetraphosphonate 6. Reaction of 7 (N = 2',3'-O-isopropylideneadenosin-5'-yl) with 2',3'-O-isopropylidenetiazofurin gave, after hydrolysis and deisopropylidenation, beta-methylene-TAD (10a), the known potent inhibitor of inosine monophosphate dehydrogenase (IMPDH). Similar reaction of 7 with benzyl 2,3-O-isopropylidene-beta-D-riboside followed by hydrolysis and deprotection afforded a new methylenebis(phosphonate) analogue of ADP-ribose 10b. Upon reaction of 7 with riboflavin, the corresponding beta-methylene-FAD (10c) was obtained. Bicyclic trisanhydride 7 prepared from (2',3'-O-isopropylidene-N-4-acetylcytidin-5'yl)methylenebis(phosphonate) was used in the synthesis of the methylenebis(phosphonate) analogues of CDP-ethanolamine 10d and CDP-dipalmitoylglycerol 10e.

  DOI：

  10.1021/ja964058i

文献信息

• Synthesis of a Methylenebis(phosphonate) Analogue of Mycophenolic Adenine Dinucleotide:  A Glucuronidation-Resistant MAD Analogue of NAD
  作者：Krystyna Lesiak、Kyoichi A. Watanabe、Alokes Majumdar、James Powell、Michael Seidman、Kristen Vanderveen、Barry M. Goldstein、Krzysztof W. Pankiewicz

  DOI：10.1021/jm970705k

  日期：1998.2.1

  Mycophenolic alcohol (MPAlc), obtained by reduction of the carboxylic group of mycophenolic acid (MPA), was coupled with 2',3'-O-isopropylideneadenosine 5'-methylenebis(phosphonate) (4) in the presence of diisopropylcarbodiimide (DIC) to give P1-(2',3'-O-isopropylideneadenosin-5'-yl)-P2-(mycophenolic alcohol-6'-yl)methylenebis(phosphonate) (8) in 32% yield. Deisopropy-lidenation of 8 with CF3COOH/H2O

  在二异丙基碳二亚胺（DIC）存在下，通过还原麦考酚酸（MPA）的羧基获得的麦考酚醇（MPAlc）与2'，3'-O-异丙基亚氨腺苷5'-亚甲基双（膦酸酯）（4）偶联得到P1-（2′，3′-O-异亚丙基腺苷-5′-基）-P2-（麦酚醇-6′-基）亚甲基双（膦酸酯）（8），产率为32％。用CF 3 COOH / H 2 O对8进行异异丙基化，得到麦考酚腺嘌呤二核苷酸（MAD）的亚甲基双（膦酸酯）类似物3。发现化合物3β-亚甲基-MAD是II型肌苷单磷酸脱氢酶（IMPDH）的有效抑制剂（Ki = 0.3 microM）以及K562细胞的生长抑制剂（IC50 = 1.5 microM）。与MPA和麦考酚醇相比，
• Pankiewicz, Krzysztof W.; Lesiak, Krystyna; Zatorski, Andrzej, Collection of Czechoslovak Chemical Communications, 1996, vol. 61, p. S92 - S95
  作者：Pankiewicz, Krzysztof W.、Lesiak, Krystyna、Zatorski, Andrzej、Watanabe, Kyoichi A.

  DOI：——

  日期：——
• Synthesis of Methylenebis(Phosphonate) Analogues of 2-, 4-, and 6-Pyridones of Nicotinamide Adenine Dinucleotide
  作者：Krzysztof Felczak、Krzysztof W. Pankiewicz

  DOI：10.1080/15257770.2011.575909

  日期：2011.7

  The synthesis of metabolically stable methylenebis(phosphonate) analogues of 2-, 4-, and 6-pyridones of nicotinamide adenine dinucleotide (NAD) is reported. In contrast to natural pyrophosphates, these NAD analogues are able to penetrate the cell membrane and can be used as probes in cellular assays.
• ANGIOGENESIS INHIBITORS
  申请人：THE JOHNS-HOPKINS UNIVERSITY

  公开号：EP1765336A2

  公开（公告）日：2007-03-28
• Angiogenesis inhibitors
  申请人：THE JOHNS-HOPKINS UNIVERSITY

  公开号：EP2803357B1

  公开（公告）日：2020-11-18