1-(3-Formylpropyl)-3,7-dimethylxanthin | 6493-12-5

• 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: 1-(3-Formylpropyl)-3,7-dimethylxanthin
• 英文别名: 1-<3-Formyl-propyl>-3,7-dimethoxy-xanthin；4-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)butanal；4-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-purin-1-yl)-butyraldehyde；4-(3,7-Dimethyl-2,6-dioxopurin-1-yl)butanal
• CAS: 6493-12-5
• 化学式: C₁₁H₁₄N₄O₃
• 分子量: 250.257
• InChiKey: MCYGVOZRGJZZRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  75.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-Formylpropyl)-3,7-dimethylxanthin 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.33h， 生成 (R)-((R)-6-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-1-yl)hex-1-en-3-yl) 2-methoxy-2-phenylacetate
  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：

  己酮可可碱 在 carboxylesterase 、 human flavin-containing monooxygenase 5 、 氧气 、 nicotinamide adenine dinucleotide 、 alcohol dehydrogenase 作用下， 以 水 为溶剂， 生成 1-(3-Formylpropyl)-3,7-dimethylxanthin
  参考文献：
  名称：

  Baeyer–Villiger单加氧酶FMO5作为药物代谢的切入点

  摘要：

  含黄素的单加氧酶（FMO）成为氧化药物代谢中的有效参与者。直到最近，这五种人类FMO同工型的功能大多与它们给含软N和S亲核分子的分子加氧的能力有关。但是，人类FMO同工型5最近被证明具有非典型活性，如Baeyer-Villiger单加氧酶。为了评估活性药物成分代谢中的这种替代进入点，我们选择并测试了在脂肪族链上带有羰基的药物分子。因此证明了萘丁美酮和己酮可可碱是两种广泛使用的药物，在体外能被有效地氧化。通过FMO5以较高的选择性生成相应的乙酸酯。拟议的途径解释了己酮可可碱的主要血浆代谢物的形成以及前药萘丁美酮向药理活性化合物的关键转化。使用重组酶，以毫克量获得了两种药物的酯衍生物，对其进行了纯化和充分表征。该协议可以潜在地扩展到其他FMO5候选底物，因为它代表了适用于API筛选和代谢物合成的有效且强大的实验台平台。

  DOI：

  10.1021/acschembio.7b00470

文献信息

• KAVAXARA, XIROSI;MATSUMURA, TAKUMI;XIRAI, YASUO;JOKODZUKA, PE
  作者：KAVAXARA, XIROSI、MATSUMURA, TAKUMI、XIRAI, YASUO、JOKODZUKA, PE

  DOI：——

  日期：——
• JPS58150594A
  申请人：——

  公开号：JPS58150594A

  公开（公告）日：1983-09-07
• Predictable Stereoselective and Chemoselective Hydroxylations and Epoxidations with P450 3A4
  作者：Aaron T. Larsen、Erin M. May、Karine Auclair

  DOI：10.1021/ja200551y

  日期：2011.5.25

  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.
• Baeyer–Villiger Monooxygenase FMO5 as Entry Point in Drug Metabolism
  作者：Filippo Fiorentini、Elvira Romero、Marco W. Fraaije、Kurt Faber、Mélanie Hall、Andrea Mattevi

  DOI：10.1021/acschembio.7b00470

  日期：2017.9.15

  into the pharmacologically active compound. Using the recombinant enzyme, the ester derivatives of both drugs were obtained in milligram amounts, purified, and fully characterized. This protocol can potentially be extended to other FMO5 candidate substrates as it represents an effective and robust bench-ready platform applicable to API screening and metabolite synthesis.

  含黄素的单加氧酶（FMO）成为氧化药物代谢中的有效参与者。直到最近，这五种人类FMO同工型的功能大多与它们给含软N和S亲核分子的分子加氧的能力有关。但是，人类FMO同工型5最近被证明具有非典型活性，如Baeyer-Villiger单加氧酶。为了评估活性药物成分代谢中的这种替代进入点，我们选择并测试了在脂肪族链上带有羰基的药物分子。因此证明了萘丁美酮和己酮可可碱是两种广泛使用的药物，在体外能被有效地氧化。通过FMO5以较高的选择性生成相应的乙酸酯。拟议的途径解释了己酮可可碱的主要血浆代谢物的形成以及前药萘丁美酮向药理活性化合物的关键转化。使用重组酶，以毫克量获得了两种药物的酯衍生物，对其进行了纯化和充分表征。该协议可以潜在地扩展到其他FMO5候选底物，因为它代表了适用于API筛选和代谢物合成的有效且强大的实验台平台。