O_10eq-β-N,N'-bis-Cbz-guanidinopropionylryanodine | 148172-32-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: O_10eq-β-N,N'-bis-Cbz-guanidinopropionylryanodine
• 英文别名: [(1R,2R,3S,6S,7S,9S,10R,11S,12R,13S,14R)-2-[3-[bis(phenylmethoxycarbonylamino)methylideneamino]propanoyloxy]-6,9,11,13,14-pentahydroxy-3,7,10-trimethyl-11-propan-2-yl-15-oxapentacyclo[7.5.1.01,6.07,13.010,14]pentadecan-12-yl] 1H-pyrrole-2-carboxylate
• CAS: 148172-32-1
• 化学式: C₄₅H₅₄N₄O₁₄
• 分子量: 874.942
• InChiKey: OODCQSZBEABRLE-AENZIACUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  63
• 可旋转键数：
  17
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  268
• 氢给体数：
  8
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  O_10eq-β-N,N'-bis-Cbz-guanidinopropionylryanodine 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 为溶剂， 以35 mg的产率得到O_10eq-β-guanidinopropionylryanodine
  参考文献：
  名称：

  Amino- and guanidinoacylryanodines: basic ryanodine esters with enhanced affinity for the sarcoplasmic reticulum calcium (2+)-release channel

  摘要：

  Amino- and guanidinoacyl esters of ryanodine were prepared to evaluate the effect of basicity on the binding affinity of these derivatives for the sarcoplasmic reticulum Ca2+-release channel (SR CRC). In the presence of DCC and DMAP Cbz-beta-alanine reacts with ryanodine in CH2Cl2 to give O10eq-Cbz-beta-alanylryanodine (3a), which on hydrogenolysis yields the beta-alanyl ester (4a). N,N'-bis-Cbz-S-methylthiourea reacts with 4a to yield beta-N,N'-bis-Cbz-guanidinopropionylryanodine (5a). O10eq-beta-guanidinopropionylryanodine (6a) is obtained on hydrogenolytic deprotection of 5a. The binding affinity of beta-alanine ester (4a) and its glycyl congener (4b) is 2-3-fold greater, and that of the beta-guanidinopropionyl ester (6a) and its acetyl congener (6b) 3-6-fold greater, than that of ryanodine. The effect of ryanodine on SR Ca2+ flux is of a biphasic nature: nanomolar levels open (activate) the channel, while micromolar levels close (deactivate) it. The base-substituted esters 4a and 6a both display a unidirectional effect: they only open the channel. An understanding of ryanodine's mode of action and the design of effective SR CRC activating and deactivating ryanoids for possible therapeutic application are major research objectives.

  DOI：

  10.1021/jm00062a003
• 作为产物：
  描述：

  ryanodine 在 palladium on activated charcoal 4-二甲氨基吡啶 、 氢气 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 4.0~25.0 ℃ 、275.79 kPa 条件下， 反应 26.0h， 生成 O_10eq-β-N,N'-bis-Cbz-guanidinopropionylryanodine
  参考文献：
  名称：

  Amino- and guanidinoacylryanodines: basic ryanodine esters with enhanced affinity for the sarcoplasmic reticulum calcium (2+)-release channel

  摘要：

  Amino- and guanidinoacyl esters of ryanodine were prepared to evaluate the effect of basicity on the binding affinity of these derivatives for the sarcoplasmic reticulum Ca2+-release channel (SR CRC). In the presence of DCC and DMAP Cbz-beta-alanine reacts with ryanodine in CH2Cl2 to give O10eq-Cbz-beta-alanylryanodine (3a), which on hydrogenolysis yields the beta-alanyl ester (4a). N,N'-bis-Cbz-S-methylthiourea reacts with 4a to yield beta-N,N'-bis-Cbz-guanidinopropionylryanodine (5a). O10eq-beta-guanidinopropionylryanodine (6a) is obtained on hydrogenolytic deprotection of 5a. The binding affinity of beta-alanine ester (4a) and its glycyl congener (4b) is 2-3-fold greater, and that of the beta-guanidinopropionyl ester (6a) and its acetyl congener (6b) 3-6-fold greater, than that of ryanodine. The effect of ryanodine on SR Ca2+ flux is of a biphasic nature: nanomolar levels open (activate) the channel, while micromolar levels close (deactivate) it. The base-substituted esters 4a and 6a both display a unidirectional effect: they only open the channel. An understanding of ryanodine's mode of action and the design of effective SR CRC activating and deactivating ryanoids for possible therapeutic application are major research objectives.

  DOI：

  10.1021/jm00062a003