N6-benzoyl-5'(R)-C-<methyl>-2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)adenosine | 107961-45-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N6-benzoyl-5'(R)-C-<methyl>-2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)adenosine
• 英文别名: N⁶-benzoyl-5'(R)-C-<methyl>-2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)adenosine
• CAS: 107961-45-5
• 化学式: C₃₃H₃₈N₆O₉S
• 分子量: 694.766
• InChiKey: WSCZWIXXBGGTQL-XMTZQEPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  49.0
• 可旋转键数：
  9.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  182.09
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  N6-benzoyl-5'(R)-C-<methyl>-2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)adenosine 在 potassium tert-butylate 作用下， 以 乙醇 、 叔丁醇 为溶剂， 反应 7.0h， 生成 5'(S)--5'-deoxy-5'-(L-homocystein-S-ylmethyl)-2',3'-O-isopropylideneadenosine
  参考文献：
  名称：

  Isozyme-specific enzyme inhibitors. 13. S-[5'(R)-['N-triphosphoamino)methyl]adenosyl]-L-homocysteine, a potent inhibitor of rat methionine adenosyltransferases

  摘要：

  A synthesis is described of the title compound and its 5'S epimer, which are two-substrate adducts of adenosine 5'-triphosphate (ATP) and L-methionine (Met) in which the C(5')H2OP system in ATP is replaced by CH(R)CH2NHP [R = L-S(CH2)2CH(NH2)CO2H]. The 5'R epimer was a potent nonselective competitive inhibitor [averaged Ki = 0.32 microM; KM(ATP)/Ki = 440] vs. ATP of the rat M-2 (normal tissue) and M-T (Novikoff ascitic hepatoma) variants of methionine adenosyltransferase. It produced simple noncompetitive inhibition (averaged Ki = 2.7 microM) vs. Met with both variants. The 5'S epimer inhibited M-T competitively vs. ATP, but was 74-fold less effective than the 5'R epimer. Replacement of the homocysteine moiety in the 5'R epimer by hydrogen markedly reduced inhibitory potency, as indicated by Ki values of 14 microM for competitive inhibition vs. ATP and 580 microM for noncompetitive inhibition vs. Met with M-2. The data suggest that the 5'R epimer can interact simultaneously with two enzymic sites. Information on the kinetic mechanism of a human counterpart of M-2 and inhibitor properties of a previously studied Met-ATP adduct are consistent with the view that the two sites might resemble those that interact with the initial products of the reaction, S-adenosylmethionine and triphosphate.

  DOI：

  10.1021/jm00388a024
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 29.0h， 生成 N6-benzoyl-5'(R)-C-<methyl>-2',3'-O-isopropylidene-5'-O-(p-toluenesulfonyl)adenosine
  参考文献：
  名称：

  Isozyme-specific enzyme inhibitors. 13. S-[5'(R)-['N-triphosphoamino)methyl]adenosyl]-L-homocysteine, a potent inhibitor of rat methionine adenosyltransferases

  摘要：

  A synthesis is described of the title compound and its 5'S epimer, which are two-substrate adducts of adenosine 5'-triphosphate (ATP) and L-methionine (Met) in which the C(5')H2OP system in ATP is replaced by CH(R)CH2NHP [R = L-S(CH2)2CH(NH2)CO2H]. The 5'R epimer was a potent nonselective competitive inhibitor [averaged Ki = 0.32 microM; KM(ATP)/Ki = 440] vs. ATP of the rat M-2 (normal tissue) and M-T (Novikoff ascitic hepatoma) variants of methionine adenosyltransferase. It produced simple noncompetitive inhibition (averaged Ki = 2.7 microM) vs. Met with both variants. The 5'S epimer inhibited M-T competitively vs. ATP, but was 74-fold less effective than the 5'R epimer. Replacement of the homocysteine moiety in the 5'R epimer by hydrogen markedly reduced inhibitory potency, as indicated by Ki values of 14 microM for competitive inhibition vs. ATP and 580 microM for noncompetitive inhibition vs. Met with M-2. The data suggest that the 5'R epimer can interact simultaneously with two enzymic sites. Information on the kinetic mechanism of a human counterpart of M-2 and inhibitor properties of a previously studied Met-ATP adduct are consistent with the view that the two sites might resemble those that interact with the initial products of the reaction, S-adenosylmethionine and triphosphate.

  DOI：

  10.1021/jm00388a024

文献信息

• Isozyme-specific enzyme inhibitors. 14. 5'(R)-C-[(L-homocystein-S-yl)methyl]adenosine 5'-(.beta.,.gamma.-imidotriphosphate), a potent inhibitor of rat methionine adenosyltransferases
  作者：Francis Kappler、Vivekananda M. Vrudhula、Alexander Hampton

  DOI：10.1021/jm00392a013

  日期：1987.9

  established by conversion of this into the known 5'(S)-C-methyl-2',3'-O-isopropylidene adenosine with Raney nickel. The alpha-amino acid residue was protected as an N-Boc methyl ester, after which the 5'-hydroxyl was phosphorylated with benzyl phosphate and dicyclohexylcarbodiimide. The phosphoanhydride bond with inorganic imidodiphosphate was then created by established methods. Finally, blocking groups were

  标题化合物是L-蛋氨酸（Met）和β，γ-亚氨基-ATP的共价加合物。在其合成过程中，通过CF3CO2H和CH3的连续作用，将5'（R）-C-（氨基甲基）-N6-苯甲酰基-5'-O-甲苯磺酰基-2'，3'-O-异丙基亚丙基腺苷的N-Boc衍生物转化。将HNO 2转化为相应的5'（R）-C-羟甲基衍生物。用L-高半胱氨酸二钠处理显然导致硫在C6'处的侵蚀，显然是通过5'，6'-环氧化物进行的，并且在脱苯甲酰化后在C5'处发生了完全立体选择性转化，从而提供了5'（R）-C- （L-高半胱氨酸-S-甲基）-2'，3'-O-异亚丙基adesine。通过将其转化为具有阮内镍的已知5'（S）-C-甲基-2'，3'-O-异亚丙基腺苷来建立5'构型。α-氨基酸残基被保护为N-Boc甲酯，然后用磷酸苄酯和二环己基碳二亚胺将5'-羟基磷酸化。然后通过确定的方法产生与无机亚氨基二磷酸的磷酸酐键。最后，在不产生其