(R)-3,7-dimethyl-1-(2-(oxiran-2-yl)propyl)-1H-purine-2,6(2H,6H)-dione | 1305318-07-3

• 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: (R)-3,7-dimethyl-1-(2-(oxiran-2-yl)propyl)-1H-purine-2,6(2H,6H)-dione
• CAS: 1305318-07-3
• 化学式: C₁₂H₁₆N₄O₃
• 分子量: 264.284
• InChiKey: VGTXRKNBOILFNX-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.39
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  74.35
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (R)-3,7-dimethyl-1-(2-(oxiran-2-yl)propyl)-1H-purine-2,6(2H,6H)-dione 在 二异丁基氢化铝 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 3-[(2R)-oxiran-2-yl]propan-1-amine
  参考文献：
  名称：

  Predictable Stereoselective and Chemoselective Hydroxylations and Epoxidations with P450 3A4

  摘要：

  Enantioselective hydroxylation of one specific methylene in the presence of many similar groups is debatably the most challenging chemical transformation. Although chemists have recently made progress toward the hydroxylation of inactivated C-H bonds, enzymes such as P450s (CYPs) remain unsurpassed in specificity and scope. The substrate promiscuity of many P450s is desirable for synthetic applications; however, the inability to predict the products of these enzymatic reactions is impeding advancement. We demonstrate here the utility of a chemical auxiliary to control the selectivity of CYP3A4 reactions. When linked to substrates, inexpensive, achiral theobromine directs the reaction to produce hydroxylation or epoxidation at the fourth carbon from the auxiliary with pro-R facial selectivity. This strategy provides a versatile yet controllable system for regio-, chemo-, and stereoselective oxidations at inactivated C-H bonds and demonstrates the utility of chemical auxiliaries to mediate the activity of highly promiscuous enzymes.

  DOI：

  10.1021/ja200551y
• 作为产物：
  描述：

  可可碱 在 过氧化氢异丙苯 、 sodium hydride 、 还原型辅酶II(NADPH)四钠盐 、 cytochrome P₄₅₀ 3A₄ 作用下， 以 二甲基亚砜 为溶剂， 反应 1.83h， 生成 (R)-3,7-dimethyl-1-(2-(oxiran-2-yl)propyl)-1H-purine-2,6(2H,6H)-dione
  参考文献：
  名称：

  Predictable Stereoselective and Chemoselective Hydroxylations and Epoxidations with P450 3A4

  摘要：

  Enantioselective hydroxylation of one specific methylene in the presence of many similar groups is debatably the most challenging chemical transformation. Although chemists have recently made progress toward the hydroxylation of inactivated C-H bonds, enzymes such as P450s (CYPs) remain unsurpassed in specificity and scope. The substrate promiscuity of many P450s is desirable for synthetic applications; however, the inability to predict the products of these enzymatic reactions is impeding advancement. We demonstrate here the utility of a chemical auxiliary to control the selectivity of CYP3A4 reactions. When linked to substrates, inexpensive, achiral theobromine directs the reaction to produce hydroxylation or epoxidation at the fourth carbon from the auxiliary with pro-R facial selectivity. This strategy provides a versatile yet controllable system for regio-, chemo-, and stereoselective oxidations at inactivated C-H bonds and demonstrates the utility of chemical auxiliaries to mediate the activity of highly promiscuous enzymes.

  DOI：

  10.1021/ja200551y

文献信息

• Regioselective Epoxidations by Cytochrome P450 3A4 Using a Theobromine Chemical Auxiliary to Predictably Produce N-Protected β- or γ-Amino Epoxides
  作者：Vanja Polic、Kin Jack Cheong、Fabien Hammerer、Karine Auclair

  DOI：10.1002/adsc.201700637

  日期：2017.11.23

  N-Protected β- and γ-amino epoxides are useful chiral synthons. We report here that the enzyme cytochrome P450 3A4 can catalyze the formation of such compounds in a regio- and stereoselective manner, even in the presence of multiple double bonds or aromatic substituents. To this end, the theobromine chemical auxiliary is used not only to control the selectivity of the enzyme, but also as a masked amine

  N-保护的β-和γ-氨基环氧化物是有用的手性合成子。我们在此报告，即使存在多个双键或芳族取代基，细胞色素P450 3A4酶也可以区域和立体选择性方式催化此类化合物的形成。为此，可可碱化学助剂不仅用于控制酶的选择性，而且还用作掩蔽的胺，并促进产物的回收。可可碱可预测地将可可碱基团中第四个碳的双键定向环氧化。与大多数催化剂不同，选择性不取决于电子或空间因素，而是取决于烯烃相对于可可碱的位置。