(3R)-3-甲基-4-[(四氢-2H-吡喃-2-基)氧基]-丁腈 | 110171-23-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧烷类
• 中文名称: (3R)-3-甲基-4-[(四氢-2H-吡喃-2-基)氧基]-丁腈
• 英文名称: (2'RS,3R)-3-methyl-4-(2-tetrahydropyranyloxy)butyronitrile
• 英文别名: (S)-3-Methyl-4-<(tetrahydropyranyl)oxy>butanenitrile；(R)-4-(tetrahydro-2-pyranyloxy)-3-methylbutanenitrile；(R)-3-cyano-2-methyl-1-propanol tetrahydropyranyl ether；(3R)-3-Methyl-4-[(tetrahydro-2H-pyran-2-YL)oxy]-butanenitrile；(3R)-3-methyl-4-(oxan-2-yloxy)butanenitrile
• CAS: 110171-23-8
• 化学式: C₁₀H₁₇NO₂
• 分子量: 183.25
• InChiKey: AZWSYGNSEHXDBG-YHMJZVADSA-N

物化性质

• 沸点：
  310.0±37.0 °C(Predicted)
• 密度：
  1.00±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  42.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  (3R)-3-甲基-4-[(四氢-2H-吡喃-2-基)氧基]-丁腈 在 palladium on activated charcoal disodium hydrogenphosphate 、 sodium amalgam 、 正丁基锂 、 氢气 、 二异丁基氢化铝 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 5.0h， 生成 (2'RS,25R)-6β-methoxy-26-(2-tetrahydropyranyloxy)-3α,5-cyclo-5α-cholestan
  参考文献：
  名称：

  氧固醇：27-羟基胆固醇及其放射性标记的类似物。

  摘要：

  我们描述了合成27-羟基胆固醇的便捷和立体选择途径。还通过该方法合成了其放射性标记的类似物，具有高比放射性（55 Ci / mmol）的22，23 di [（3）H] -27-羟基胆固醇。朱莉娅类固醇22砜与醛的缩合反应导致类固醇主链上添加了23-27碳侧链结构单元。在该反应中形成的β-羟基砜部分被钠汞齐还原生成22-23个不饱和键。用氢或tri提供的底物进一步还原以合成标题化合物。

  DOI：

  10.1016/s0039-128x(00)00099-4
• 作为产物：
  描述：

  3,4-二氢-2H-吡喃 在 吡啶 、 lithium aluminium tetrahydride 、 对甲苯磺酸 作用下， 以 乙醚 、 二甲基亚砜 为溶剂， 反应 52.0h， 生成 (3R)-3-甲基-4-[(四氢-2H-吡喃-2-基)氧基]-丁腈
  参考文献：
  名称：

  对映体纯的甲基化氧代苯丙氨酸衍生物的合成和生化药理作用。

  摘要：

  以前使用外消旋混合物而不是旋光性化合物进行了在吡咯烷酮环的3-，4-和5-位带有取代基的甲基化氧代苯丁胺衍生物的药理研究。描述了在3位和4位的旋光甲基化氧代苯丙氨酸衍生物的合成和放射性配体结合数据。3位和4位衍生物之间存在明显的药理差异。4位对映异构体具有弱的，近似相等的亲和力和类似拮抗剂的特征，而3位对映异构体具有显着不同的亲和力和部分激动剂类似的特征。

  DOI：

  10.1021/jm00075a007

文献信息

• The synthesis and biochemical pharmacology of enantiomerically pure methylated oxotremorine derivatives
  作者：Eugene J. Trybulski、Jing Zhang、Richard H. Kramss、Richard M. Mangano

  DOI：10.1021/jm00075a007

  日期：1993.11

  Previous pharmacological studies of methylated oxotremorine derivatives bearing substituents at the 3-, 4-, and 5-positions of the pyrrolidinone ring have been conducted using racemic mixtures, and not with optically active compounds. The synthesis and radioligand binding data of optically active, methylated oxotremorine derivatives at the 3- and 4-positions are described. There are significant pharmacological

  以前使用外消旋混合物而不是旋光性化合物进行了在吡咯烷酮环的3-，4-和5-位带有取代基的甲基化氧代苯丁胺衍生物的药理研究。描述了在3位和4位的旋光甲基化氧代苯丙氨酸衍生物的合成和放射性配体结合数据。3位和4位衍生物之间存在明显的药理差异。4位对映异构体具有弱的，近似相等的亲和力和类似拮抗剂的特征，而3位对映异构体具有显着不同的亲和力和部分激动剂类似的特征。
• IMPROVED SYNTHESIS OF (<i>R</i>)- AND (<i>S</i>)-β-METHYL-γBUTYROLACTONE
  作者：Keith R. Buszek、Nagaaki Sato

  DOI：10.1080/00304940009356765

  日期：2000.10

  preparation of (S)-(-)-P-methyl-y-butyrolactone’ from methyl (R)-(-)-3-hydroxy-2-methylpropionate (Roche ester).’ The synthesis unfortunately suffers from an unacceptably low-yielding (23%) nitrile hydrolysis-lactonization reaction in the last step. The inefficiency of this process precluded the procurement of the large quantity of material needed for our work. We now report a substantially improved and simplified

  作为设计和合成基于四氢呋喃支架的光学活性溶剂用于对映选择性有机和无机转化的研究计划的一部分，我们需要非常大量的标题化合物。Mori 发表了“从 (R)-(-)-3-羟基-2-甲基丙酸甲酯（罗氏酯）制备 (S)-(-)-P-甲基-γ-丁内酯”的五步程序.' 不幸的是，该合成在最后一步发生了无法接受的低产率 (23%) 腈水解-内酯化反应。这一过程效率低下，无法采购我们工作所需的大量材料。我们现在报告了一种显着改进和简化的方法，用于以 87% 的产率将腈 1 转化为内酯 2。
• On the mechanism of Lewis acid promoted ene cyclizations of .omega.-unsaturated aldehydes
  作者：James A. Marshall、Marc W. Andersen

  DOI：10.1021/jo00048a016

  日期：1992.10

  The diastereomerically labeled d1 enals 1 and 2 were prepared from (S)-3-bromo-2-methylpropanol 5 by a sequence involving homologation to the allylic alcohol 13 and Sharpless epoxidation to either the alpha- or the beta-epoxide diastereomers 14 or 15. Reduction with LiAlD4 afforded the diastereomerically deuterated diols 16 and 20, respectively. Deoxygenation of the thionocarbonate derivatives 17 and 21 followed by THP ether cleavage and Swern oxidation afforded aldehydes 1 and 2. The undeuterated aldehyde 28 was similarly prepared. Cyclization of 1 and 2 with Me2AlCl afforded the cis-(E)-ethylidenecyclohexanols 3 and 4, respectively, as the major products in accord with a mechanism involving internal proton or deuteron transfer from the vinylic CHD grouping to the aldehyde carbonyl. Product ratios (E:Z, cis:trans) from the two aldehydes were significantly different, indicative of a substantial isotope effect.
• Stereospecificity in allergic contact dermatitis to simple substituted methylene lactones derivatives
  作者：Henri Mattes、Kaoru Hamada、Claude Benezra

  DOI：10.1021/jm00394a003

  日期：1987.11

  The enantiomers of beta,gamma-dimethyl- and beta-methyl-alpha-methylene-gamma-butyrolactones have been synthesized stereospecifically from glutamic acid and beta-hydroxy isobutyric acid, respectively. Guinea pigs have been sensitized (Freund complete adjuvant technique) and tested to them. Both enantiomers of beta-methyl lactone as well as (+)-beta,gamma-dimethyl lactone induced enantiospecific allergic contact dermatitis (ACD); in turn, (-)-beta,gamma-dimethyl lactone showed no specificity. An interpretation is proposed.
• Axially Chiral 1,7-Naphthyridine-6-carboxamide Derivatives as Orally Active Tachykinin NK₁ Receptor Antagonists:  Synthesis, Antagonistic Activity, and Effects on Bladder Functions
  作者：Hideaki Natsugari、Yoshinori Ikeura、Izumi Kamo、Takenori Ishimaru、Yuji Ishichi、Akira Fujishima、Toshimasa Tanaka、Fumiko Kasahara、Mitsuru Kawada、Takayuki Doi

  DOI：10.1021/jm990220r

  日期：1999.9.1

  Cyclic analogues of N-[3,5-bis(trifluoromethyl)benzyl]-7,8-dihydro-N,7-dimethyl-5-(4-methylphenyl)-8-oxo-1,7-naphthyridine-6-carboxamide (1) having a 6-9-membered ring (6-9) were synthesized and evaluated for NK1 antagonistic activities. The 8-membered ring compound with a beta-methyl group at the C-(9)-position, (aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10,-11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g][1,7]naphthyridine-6,13-di-one [(aR,9R)-8b], was atropodiastereoselectively synthesized by cyclization of a chiral intermediate, 10g. On the other hand, the 7-membered ring compound with a beta-methyl group at the C-(9)-position [(9S)-7b] was obtained as an equilibrium mixture of atropisomers with a ratio of ca. 3:2 in solution at room temperature (measured by NMR in CDCl3). Compounds (9S)-7b and (aR,9R)-8b exhibited excellent antagonistic activities both in vitro [IC50 (inhibition of [I-125]BH-SP binding in human IM-9 cells) = 0.28 and 0.45 nM, respectively] and in vivo (iv and po). Significantly, the in vitro activity of (aR,9R)-8b was ca. 750-fold higher than that of its enantiomer (aS,9S)-8b, ca. 40-fold higher than its atropisomer (aS,9R)-8b, and ca. 20-fold higher than its diastereomer (aR,9S)-8b. The structure-activity relationships in this series, along with the X-ray analysis of (aR,9R)-8b, indicated that the stereochemistry around the -C-(6)(=O)-N-(7)-CH2Ar moiety is important for NK1 receptor recognition. The NK1 antagonists showed effects on bladder functions in guinea pigs upon intravenous injection: i.e., the antagonists increased the shutdown time of distension-induced rhythmic bladder contractions and the bladder volume threshold, and the effects on the shutdown time were found to correlate well with the NK1 antagonistic activities. Compound (aR,9R)-8b has been identified as a potential clinical candidate for the treatment of bladder function disorders.