(S)-4-(1-异丙基)-3-(1-氧代丁基)-2-恶唑烷酮 | 80697-93-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: (S)-4-(1-异丙基)-3-(1-氧代丁基)-2-恶唑烷酮
• 中文别名: 1-O-{[(E)-1,2,3-噻二唑-5-基甲亚基]氨基}-D-葡萄吡喃糖酮酸
• 英文名称: 3-(1-oxobutyl)-4-(S)-(1-methylethyl)-2-oxazolidinone
• 英文别名: (4S)-3-butanoyl-4-(1-methylethyl)-2-oxazolidinone；(4S)-3-butyroyl-4-isopropyl-2-oxazolidine；(S)-4-(1-Isopropyl)-3-(1-oxobutyl)-2-oxazolidinone；(4S)-3-butanoyl-4-propan-2-yl-1,3-oxazolidin-2-one
• CAS: 80697-93-4
• 化学式: C₁₀H₁₇NO₃
• 分子量: 199.25
• InChiKey: ROUBSHUEYGPLRH-MRVPVSSYSA-N

物化性质

• 沸点：
  315.2±11.0 °C(Predicted)
• 密度：
  1.084±0.06 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、乙醇（微溶）、甲醇（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-4-(1-异丙基)-3-(1-氧代丁基)-2-恶唑烷酮 在 W-2 RaNi 、 lithium diisopropyl amide 作用下， 反应 0.5h， 生成 -4-(1-methylethyl)-3-(2-methyl-1-oxobutyl)-2-oxazolidinone
  参考文献：
  名称：

  手性O-甲硅烷基化酰亚胺烯醇化物的不对称烷基化和亚磺酰基化。

  摘要：

  手性O-甲硅烷基化的烯醇盐（5）可以被1,3-二氟硼酸二硼鎓或PhSCl高非对映选择性（〜20：1）烷基化或亚磺酰基化。相反，苯硫基烷基化以非对映选择性低的方式进行。

  DOI：

  10.1016/s0040-4039(00)95033-0
• 作为产物：
  描述：

  L-缬氨醇 在 正丁基锂 、 potassium carbonate 作用下， 反应 0.5h， 生成 (S)-4-(1-异丙基)-3-(1-氧代丁基)-2-恶唑烷酮
  参考文献：
  名称：

  Thiopyrano[2,3,4-cd]indoles as 5-Lipoxygenase Inhibitors: Synthesis, Biological Profile, and Resolution of 2-[2-[1-(4-Chlorobenzyl)-4-methyl-6-[(5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]ethoxy]butanoic Acid

  摘要：

  Leukotriene biosynthesis inhibitors have potential as new therapies for asthma and inflammatory diseases. The recently disclosed thiopyrano[2,3,4-cd] indole class of 5-lipoxygenase (5-LO) inhibitors has been investigated with particular emphasis on the side chain bearing the acidic functionality. The SAR studies have shown that the inclusion of a heteroatom (O or S) in conjunction with an alpha-ethyl substituted acid leads to inhibitors of improved potency. The most potent inhibitor prepared contains a 2-ethoxybutanoic acid side chain. This compound, 14d (2-[2-[1-(4-chlorobenzyl)-4-methyl-6-[ (5-phenylpyridin-2-yl)methoxy]-4,5-dihydro-1H-thiopyrano[2,3,4-cd]indol-2-yl]ethoxy]-butanoic acid, L-699,333), inhibits 5-HPETE production by human 5-LO and LTB(4) biosynthesis by human PMN leukocytes and human whole blood (IC(50)s Of 22 nM, 7 nM and 3.8 mu M, respectively). The racemic acid 14d has been shown to be functionally active in a rat pleurisy model (inhibition of LTB(4), ED(50) = 0.65 mg/kg, 6 h pretreatment) and in the hyperreactive rat model of antigen-induced dyspnea(50% inhibition at 2 and 4 h pretreatment; 0.5 mg/kg po). In addition, 14d shows excellent functional activity against antigen-induced bronchoconstriction in the conscious squirrel monkey [89% inhibition of the increase in R(L) and 68% inhibition in the decrease in C-dyn (0.1 mg/kg, n = 3)] and in the conscious sheep models of asthma (iv infusion at 2.5 mu g/kg/min). Acid 14d is highly selective as an inhibitor of 5-LO activity when compared to the inhibition of human 15-LO, porcine 12-LO and ram seminal vesicle cyclooxygenase (IC50 > 5 mu M) Or competition in a FLAP binding assay (IC5O > 10 mu M). Resolution of 14d affords 14g, the most potent diastereomer, which inhibits the 5-HPETE production of human 5-LO and LTB(4) biosynthesis of human PMN leukocytes and human whole blood with IC(50)s Of 8 nM, 4 nM, and 1 mu M respectively. The in vitro and in vivo profile of 14d is comparable to that of MK-0591, which has showed biochemical efficacy in inhibiting ex vivo LTB(4) biosynthesis and urinary LTE(4) excretion in clinical trials.

  DOI：

  10.1021/jm00034a013

文献信息

• Oxidative Homocoupling of Chiral 3-Arylpropanoic Acid Derivatives. Application to Asymmetric Synthesis of Lignans
  作者：Naoki Kise、Takako Ueda、Kimikage Kumada、Yuichi Terao、Nasuo Ueda

  DOI：10.1021/jo991317o

  日期：2000.1.1

  TiCl(4), PhI(OAc)(2), or CuCl(2) as an oxidant. The stereoselectivity can be explained by a radical coupling mechanism. Optically active dibenzylbutyrolactone lignans, such as (-)-hinokinin and (-)-dimethylmatairesinol, and dibenzylbutanediol lignans, such as (-)-dihydrocubebin and (-)-dimethylsecoisolariciresinol, were synthesized from the major R,R-dimers. The oxidative coupling of (4R, 5S)-1-(3-arylpropanoyl)-3

  （4S）-3-（3-芳基丙酰基）-4-异丙基-2-恶唑烷酮和（4R，5S）-1-（3-芳基丙酰基）-3,4-二甲基-5-苯基的烯醇锂的氧化均偶联-2-咪唑啉酮类化合物以TiCl（4），PhI（OAc）（2）或CuCl（2）为氧化剂立体选择性地给出了相应的R，R-二聚体。立体选择性可以通过自由基偶联机理来解释。由主要的R，R-二聚体合成了光学活性的二苄基丁内酯木脂素，例如（-）-激肽和（-）-二甲基麦角甾醇，和二苄基丁二醇木脂素，例如（-）-二氢立方体素和（-）-二甲基-异异二十二烯醇。（4R，5S）-1-（3-芳基丙酰基）-3,4-二甲基-5-苯基-2-咪唑啉酮与LDA-I（2）的氧化偶合主要得到R，S-二聚体，该结果可以用S（N）2机制来解释。
• Syntheses of isotopically labelled L-α-amino acids with an asymmetric centre at C-3
  作者：John R. Harding、Rachael A. Hughes、Nicholas M. Kelly、Andrew Sutherland、Christine L. Wilis

  DOI：10.1039/b005172l

  日期：——

  Approaches are described to the synthesis of a series of isotopically labelled L-α-amino acids each with an asymmetric centre at C-3, including isoleucine, allo-isoleucine, threonine and allo-threonine. The methods may be simply adapted for the selective incorporation of an isotopic label at each site of L-valine including the selective labelling of either diastereotopic methyl group with carbon-13

  描述了合成一系列同位素标记的L -α-氨基酸的方法，每个氨基酸在C-3处具有不对称中心，包括异亮氨酸， 同种异亮氨酸， 苏氨酸 和 异基因-苏氨酸。所述方法可以简单地适于将同位素标记物选择性地掺入到所述细胞的每个位点。大号缬氨酸 包括对非对映异构体的选择性标记 甲基 碳13和/或氘和 贴标 的 胺 和 氮15。
• Chemo-enzymatic synthesis of isotopically labelled L-Valine, L-Isoleucine and allo-isoleucine
  作者：Nicholas M. Kelly、R. Gordon Reid、Christine L. Wellis、Peter L. Winton

  DOI：10.1016/0040-4039(96)00053-6

  日期：1996.2

  catalysed reactions (Candida cylindracea lipase to hydroluse the ester and leucine dehydrogenase to catalyse the reductive amination of the ketone). This strategy may be simply adapted for the selective labelling of each site of the L-amino acid.

  （3的合成[R ）- [4,4,4- d 3 ] -L-缬氨酸，[ 15 N] -L -异亮氨酸和[ 15 N] -异基因从纯手2烷基化的羧酸-异亮氨酸中描述。该方法涉及羧酸的一碳同系化，得到相应的β-取代的α-酮酸酯，该酯可通过一锅法直接转化为α-氨基酸，涉及两个酶催化的反应（念珠菌脂肪酶转化为水解酶）。酯和亮氨酸脱氢酶催化酮的还原胺化反应）。该策略可以简单地适用于L-氨基酸的每个位点的选择性标记。
• Stereoselective Michael Addition Reactions of Acylated Oxazolidinones to Ethyl 3-Trifluoromethylacrylate
  作者：Takashi Yamazaki、Jiro Haga、Tomoya Kitazume

  DOI：10.1246/cl.1991.2175

  日期：1991.12

  Michael addition reactions of acyl oxazolidinones to ethyl 3-trifluoromethylacrylate were found to proceed smoothly with a high degree of diastereo- as well as diastereofacial selectivity at the new carbon–carbon bond.

  发现酰基恶唑烷酮与 3-三氟甲基丙烯酸乙酯的迈克尔加成反应在新的碳-碳键处以高度的非对映选择性和非对映选择性顺利进行。
• Intra- and intermolecular hetero-Diels-Alder reactions. 34. Enantioselective total synthesis of the mycotoxin (-)-talaromycin B by a hetero Diels-Alder reaction
  作者：Lutz F. Tietze、Christoph Schneider

  DOI：10.1021/jo00007a040

  日期：1991.3

  (-)-Talaromycin B was formed in an overall yield of 5% in nine steps via a hetero Diels-Alder reaction of the exocyclic vinyl ether 3 and methyl O-benzoyldiformylacetate (4) as the key transformation. The enantiomerically pure vinyl ether 3 was prepared in 28% yield and ee > 98% by alkylation of the N-butyryloxazolidinone 5 with 1-bromo-4-(trimethylsilyl)-2butyne (6), followed by a reduction-hydrogenation-protodesilylation sequence to give 9, which was transformed into 3 by iodoetherification with iodine and elimination with DBU. Methyl O-benzoyldiformylacetate (4) was synthesized by formylation of methyl 3,3-dimethoxypropionate, followed by benzoylation. The cycloaddition of 3 and 4 gave predominantly the desired adduct 11 together with the other three possible diastereomers. (-)-Talaromycin B (2) was obtained from 11 by reduction with DIBAL-H and stereoselective hydrogenation with platinum as catalyst. For purification purposes, 2 was transformed into a cyclic silyl ether by reaction with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane.

  (-)-塔拉霉素B通过一个包含9步反应的合成路线制得，总产率为5%。其中关键的一步是将外环乙烯基醚3与甲基邻苯甲酰二甲酰醋酸酯4通过异氧戴斯-阿尔德反应生成。对映体纯的乙烯基醚3由N-丁酰氧杂二环酮5与1-溴-4-(三甲基硅基)-2-丁炔6的烷基化反应制得，产率为28%，ee值大于98%。随后经过还原、氢化及脱硅基等一系列反应得到9，再通过与碘的醚化反应及DBU引发的消除反应得到3。甲基邻苯甲酰二甲酰醋酸酯4由甲基3,3-二甲氧基丙酸酯经过甲酰化和苯甲酰化反应制得。3和4的环加成反应主要生成目标加成物11，同时也伴随其他三种可能的非对映异构体。(-)-塔拉霉素B(2)由11经DIBAL-H还原及Pt催化下的立体选择性氢化反应制得。为了便于纯化，2与1,3-二氯-1,1,3,3-四异丙基二硅氧烷反应转化为环状硅醚。