2-amino-6-deamino-2-dehydro-6-hydroxy-4'β,5'-dihydrogriseolic acid | 107937-45-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-amino-6-deamino-2-dehydro-6-hydroxy-4'β,5'-dihydrogriseolic acid
• 英文别名: (2R,3R,3aS,5S,6aS)-2-(2-amino-6-oxo-1H-purin-9-yl)-5-[carboxy(hydroxy)methyl]-3-hydroxy-3,3a,6,6a-tetrahydro-2H-furo[3,2-b]furan-5-carboxylic acid
• CAS: 107937-45-1；110267-51-1
• 化学式: C₁₄H₁₅N₅O₉
• 分子量: 397.301
• InChiKey: LRBZVDLUWIGYNF-GBKZDHLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  219
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  dimethyl 1'β-acetoxy-O2',O7'-dibenzoyl-1'-deadenino-4'β,5'-dihydrogriseolate 在 sodium hydroxide 、 三氟甲磺酸三甲基硅酯 、 氨 作用下， 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 124.0h， 生成 2-amino-6-deamino-2-dehydro-6-hydroxy-4'β,5'-dihydrogriseolic acid
  参考文献：
  名称：

  Studies on griseolic acid derivatives. VII. Synthesis and phosphodiesterase inhibitory activity of the C4' - C5' hydrogenated products of griseolic acid and their base-exchanged derivatives.

  摘要：

  研究了灰苏氨酸 C4'-C5' 双键的加成反应。通过还原 4'- 位上含有卤素的加合物，得到了 C4'-C5' 二氢麦角苷酸。C4'-C5' 二氢衍生物的两个五元环的环连接处为全 "顺 "构型。对受保护的二氢甘草次苷酸进行乙酰分解，可得到相应的 1'- 乙酰氧基糖衍生物。将这种糖衍生物与硅烷化碱基反应，可得到二氢草胆酸的鸟嘌呤和尿嘧啶衍生物。C4'-C5' 顺式二氢麦角苷酸衍生物的环核苷酸磷酸二酯酶（PDE）抑制活性弱于麦角苷酸。C4'-C5' 顺式二氢草胆酸的尿嘧啶衍生物完全丧失了对 3'，5'-环单磷酸腺苷（cAMP）和 3'，5'-环单磷酸鸟苷（cGMP）PDE 的抑制活性，而鸟嘌呤衍生物对 cAMP PDE 的抑制活性有所降低，但对 cGMP PDE 的抑制活性保持不变。同样明显的是，从石杉酸的同一培养液中作为次要产物获得的 C4'-C5' 反式二氢衍生物与石杉酸具有几乎相同的抑制活性。

  DOI：

  10.1248/cpb.36.3760

文献信息

• Studies on griseolic acid derivatives. VII. Synthesis and phosphodiesterase inhibitory activity of the C4' - C5' hydrogenated products of griseolic acid and their base-exchanged derivatives.
  作者：YOSHINOBU MUROFUSHI、MISAKO KIMURA、HARUMITSU KUWANO、YASUTERU IIJIMA、MITSUO YAMAZAKI、MASAKATSU KANEKO

  DOI：10.1248/cpb.36.3760

  日期：——

  Addition reactions of the C4'-C5' double bond of griseolic acid were investigated. C4'-C5' Dihydrogriseolic acid was obtained by reduction of the adduct having halogen at the 4'-position. The ring juncture of the two five-membered rings of the C4'-C5' dihydro derivatives was of all- “cis” configuration. Acetolysis of the protected dihydrogriseolic acid gave the corresponding 1'-acetoxy sugar derivative. Reaction of this sugar derivative with silylated bases gave guanine and uracil derivatives of the dihydrogriseolic acid. The cyclic nucleotide phosphodiesterase (PDE)-inhibitory activity of the C4'-C5' cis dihydrogriseolic acid derivative was weaker than that of griseolic acid. The uracil derivative of C4'-C5' cis dihydrogriseolic acid completely lost the inhibitory activity against both adenosine 3', 5'-cyclic monophosphate (cAMP) and guanosine 3', 5'-cyclic monophosphate (cGMP) PDE, whereas the guanine derivative showed reduced inhibitory activity against cAMP PDE, but retained its activity against cGMP PDE. It was also apparent that the C4'-C5' trans dihydro derivative which was obtained as a minor product from the same culture broth of griseolic acid had almost the same inhibitory activity as griseolic acid.

  研究了灰苏氨酸 C4'-C5' 双键的加成反应。通过还原 4'- 位上含有卤素的加合物，得到了 C4'-C5' 二氢麦角苷酸。C4'-C5' 二氢衍生物的两个五元环的环连接处为全 "顺 "构型。对受保护的二氢甘草次苷酸进行乙酰分解，可得到相应的 1'- 乙酰氧基糖衍生物。将这种糖衍生物与硅烷化碱基反应，可得到二氢草胆酸的鸟嘌呤和尿嘧啶衍生物。C4'-C5' 顺式二氢麦角苷酸衍生物的环核苷酸磷酸二酯酶（PDE）抑制活性弱于麦角苷酸。C4'-C5' 顺式二氢草胆酸的尿嘧啶衍生物完全丧失了对 3'，5'-环单磷酸腺苷（cAMP）和 3'，5'-环单磷酸鸟苷（cGMP）PDE 的抑制活性，而鸟嘌呤衍生物对 cAMP PDE 的抑制活性有所降低，但对 cGMP PDE 的抑制活性保持不变。同样明显的是，从石杉酸的同一培养液中作为次要产物获得的 C4'-C5' 反式二氢衍生物与石杉酸具有几乎相同的抑制活性。