1-(4-hydroxy-butyl)-3,7-dimethyl-3,7-dihydro-purine-2,6-dione | 75587-07-4

• 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-(4-hydroxy-butyl)-3,7-dimethyl-3,7-dihydro-purine-2,6-dione
• 英文别名: 3,7-dihydro-1-(4-hydroxybutyl)-3,7-dimethylpurine-2,6-dione；1-(4-hydroxybutyl)-3,7-dimethyl-1H-purine-2,6(2H,6H)-dione；1-(4-hydroxybutyl)-3,7-dimethylpurine-2,6-dione
• CAS: 75587-07-4
• 化学式: C₁₁H₁₆N₄O₃
• 分子量: 252.273
• InChiKey: ZPPPVKNBVVLEAQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  78.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-hydroxy-butyl)-3,7-dimethyl-3,7-dihydro-purine-2,6-dione 在 4-二甲氨基吡啶 、 碘苯二乙酸 、 TEMPO on colloidal silica 、 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 2.33h， 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 作用下， 以 水 为溶剂， 生成 1-(4-hydroxy-butyl)-3,7-dimethyl-3,7-dihydro-purine-2,6-dione
  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

• Mechanistic investigations of ruthenium(III) catalyzed oxidation of pentoxifylline by copper(III) periodate complex in aqueous alkaline medium
  作者：Shweta J. Malode、Jyothi C. Abbar、Sharanappa T. Nandibewoor

  DOI：10.1007/s00706-011-0458-x

  日期：2011.5

  AbstractThe kinetics of the oxidation of ruthenium(III)-catalyzed oxidation of pentoxifylline (PTX) by diperiodatocuprate(III) (DPC) in aqueous alkaline medium at a constant ionic strength of 0.30 mol dm−3 was studied spectrophotometrically. The reaction between PTX and DPC in alkaline medium in the presence of Ru(III) exhibits 1:2 stoichiometry (PTX:DPC). The reaction was of first order in DPC, less

  摘要以分光光度法研究了在碱性水溶液中，在恒定的离子强度为0.30 mol dm -3的条件下，二吡啶十二酸铜（III）（DPC）催化钌（III）催化氧化己酮可可碱（PTX）的动力学。在Ru（III）存在的情况下，PTX与DPC在碱性介质中的反应具有1：2的化学计量比（PTX：DPC）。反应第一阶中DPC，小于在[PTX]的单元顺序和[OH - ]和负分数阶在[IO 4 -]。[Ru（III）]中的顺序是统一的。在反应中观察到自由基的干预。通过TLC和包括LC-MS在内的光谱研究确定了主要产品。已经表明，在碱性介质中的氧化反应是通过Ru（III）-PTX配合物进行的，该配合物与单过碘合十二碳酸盐（III）反应，在速率确定步骤中分解，然后进行快速步骤，得到产物。计算了机理不同步骤中涉及的反应常数。计算和讨论了有关该机构慢步的激活参数，并确定了热力学量。已经鉴定出催化剂和氧化剂的活性种类。 图形概要
• Osmium(VIII) catalyzed and uncatalyzed oxidation of a hemorheologic drug Pentoxifylline by alkaline copper(III) periodate complex: A comparative kinetic and mechanistic approach
  作者：Jyothi C. Abbar、Shweta J. Malode、Sharanappa T. Nandibewoor

  DOI：10.1016/j.poly.2010.07.009

  日期：2010.10

  The oxidation of a hemorheologic drug, Pentoxifylline (PTX) by diperiodatocuprate(III) (DPC) has been investigated both in the absence and presence of Osmium(VIII) catalyst in aqueous alkaline medium at a constant ionic strength of 0.30 moldm(-3) spectrophotometrically. The stoichiometry was same in both the cases, i.e., [PTX]/[DPC] = 1:2. In both catalyzed and uncatalyzed reactions, the order of the reaction with respect to [DPC] was unity while the order with respect to [PTX] was <1 over the concentration range studied. The rate increased with an increase in [OH-] and decreased with an increase in [IO4-] in both the cases. The order with respect to [Os(VIII)] was unity. The reaction rates revealed that Os(VIII) catalyzed reaction was about sixfold faster than the uncatalyzed reaction. The reaction products were identified by TLC and spectral studies including LC-MS. Suitable mechanisms were proposed. The reaction constants involved in different steps of the reaction mechanisms were calculated for both cases. The catalytic constant (K-C) was also calculated for catalyzed reaction at different temperatures. The activation parameters with respect to slow step of the mechanism and also the thermodynamic quantities were determined. Kinetic experiments suggest that [Cu(H2IO6)(H2O)(2)] is the reactive copper(III) species and [OsO4(OH)(2)](2-) is the reactive Os(VIII) species. (C) 2010 Elsevier Ltd. All rights reserved.
• US5780476A
  申请人：——

  公开号：US5780476A

  公开（公告）日：1998-07-14
• US5866576A
  申请人：——

  公开号：US5866576A

  公开（公告）日：1999-02-02
• US6121270A
  申请人：——

  公开号：US6121270A

  公开（公告）日：2000-09-19